EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)
Study Details
Study Description
Brief Summary
The aim of the study is to investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Empagliflozin
|
Drug: Empagliflozin
once daily
Other Names:
|
Placebo Comparator: Placebo
|
Drug: Placebo
once daily
|
Outcome Measures
Primary Outcome Measures
- Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to the first event of adjudicated cardiovascular (CV) death or adjudicated hospitalisation for heart failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
Secondary Outcome Measures
- Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) [From randomisation until completion of the planned treatment phase, up to 1040 days.]
Reported is the total number of HHF events (first and recurrent) which occurred. All data up to the end of the planned treatment period (including the data after the end of treatment for patients not completing the treatment period as planned) from all randomised patients was used.
- eGFR (CKD-EPI) cr Slope of Change From Baseline [Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days.]
Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) [mL/min/1.73m2] slope of change from baseline. Available on-treatment change-from-baseline data were to be used. Patients without on-treatment data after randomisation were not to be included in this analysis. Slope represents the long term effect on eGFR. Timepoints after baseline were included in calculation of slope of change from baseline. Descriptive statistic (mean(standard error)) is reported.
- Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to the first event in the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), renal transplant, or sustained reduction in Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
- Time to First Adjudicated Hospitalisation for Heart Failure (HHF) [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to first adjudicated Hospitalisation for Heart Failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
- Time to Adjudicated Cardiovascular (CV) Death [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to adjudicated CV (Cardiovascular) death. The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
- Time to All-cause Mortality [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to all-cause mortality. The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
- Time to Onset of Diabetes Mellitus (DM) [From randomisation until completion of the planned treatment period, up to 1040 days.]
Time to onset of DM (Glycated haemoglobin (HbA1c) ≥6.5% or as diagnosed by the investigator) in patients with pre-DM (no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of 5.7 to <6.5%). The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.
- Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52 [Assessed at baseline, week 12, week 32 and week 52.]
Change from baseline in KCCQ (Kansas City cardiomyopathy questionnaire) clinical summary score at Week 52. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, selfefficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status. For patients who died, a worst score (score of 0) is imputed at all subsequent scheduled visits after the date of death. Standard error is adjusted standard error. Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported.
- Number of All-cause Hospitalizations (First and Recurrent) [From randomisation until completion of the planned treatment phase, up to 1040 days.]
Number of all-cause hospitalizations (first and recurrent).
Eligibility Criteria
Criteria
Inclusion criteria:
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Male or female patient age >= 18 years at screening. For Japan only: Age >= 20 years at screening
-
Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association Classification) class II-IV and reduced EF (Ejection Fraction) (LVEF (Left Ventricular Ejection Fraction) <=40%) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide)
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If EF >= 36% to <= 40%: NT-proBNP >= 2500 pg/ml or patients without AF (atrial fibrillation/atrial flutter) and NT-proBNP >= 5000 pg/ml for patients with AF
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If EF >= 31% to <= 35%: NT-proBNP >= 1000 pg/ml for patients without AF and NT-proBNP >=2000 pg/ml for patients with AF
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If EF<= 30%: NT-proBNP >= 600 pg/ml for patients without AF and NT-proBNP >=1200 pg/ml for patients with AF
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EF ≤ 40% and hospitalization for heart failure in the past 12 months: NTproBNP ≥ 600 pg/ml for patients without AF and NT-proBNP >= 1200 pg/ml for patients with AF
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Appropriate dose of medical therapy for HF consistent with prevailing local and international CV (Cardiovascular) guidelines, stable for at least 1 week prior to Visit 1
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Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines
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Signed and dated written ICF (Informed Consent Form)
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Further inclusion criteria apply
Exclusion criteria:
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Myocardial infarction, coronary artery bypass graft surgery, or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1
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Heart transplant recipient, or listed for heart transplant
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Acute decompensated HF
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Systolic blood pressure (SBP) >= 180 mmHg at Visit 2.
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Symptomatic hypotension and/or a SBP < 100 mmHg
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Indication of liver disease
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Impaired renal function, defined as eGFR (Estimated Glomerular Filtration Rate) < 20 mL/min/1.73 m2 (CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration Equation)) or requiring dialysis
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History of ketoacidosis
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Current use or prior use of a SGLT (Sodium-glucose co-transporter)-2 inhibitor or combined SGLT-1 and 2 inhibitor
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Currently enrolled in another investigational device or drug study
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Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors
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Women who are pregnant, nursing, or who plan to become pregnant while in the trial
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Further exclusion criteria apply
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | La Mesa Cardiac Center | La Mesa | California | United States | 91942 |
2 | Long Beach Center for Clinical Research | Long Beach | California | United States | 90807 |
3 | VA Greater Los Angeles Healthcare System | Los Angeles | California | United States | 90073 |
4 | Merced Vein and Vascular Center | Merced | California | United States | 95340 |
5 | University of California Irvine | Orange | California | United States | 92865 |
6 | Covigilant Research, LLC | Riverside | California | United States | 92506 |
7 | University of California | Torrance | California | United States | 90502 |
8 | Orange County Research Center | Tustin | California | United States | 92780 |
9 | Blue Coast Cardiology | Vista | California | United States | 92083 |
10 | South Denver Cardiology Associates, PC | Littleton | Colorado | United States | 80120 |
11 | Integrated Heart Care | Boca Raton | Florida | United States | 33434 |
12 | Morton Plant Mease Health Care | Clearwater | Florida | United States | 33756 |
13 | Nature Coast Clinical Research | Crystal River | Florida | United States | 34429 |
14 | Avail Clinical Research, LLC | DeLand | Florida | United States | 32720 |
15 | Holy Cross Hospital | Fort Lauderdale | Florida | United States | 33308 |
16 | Integrative Research Associates | Fort Lauderdale | Florida | United States | 33312 |
17 | Nature Coast Clinical Research | Inverness | Florida | United States | 34452 |
18 | East Coast Institute for Research, LLC | Jacksonville | Florida | United States | 32216 |
19 | Jacksonville Center for Clinical Research | Jacksonville | Florida | United States | 32216 |
20 | Cardiovascular Research Center of South Florida | Miami | Florida | United States | 33173 |
21 | Peninsula Research, Inc. | Ormond Beach | Florida | United States | 32174 |
22 | Cardiology Consultants, Inc | Pensacola | Florida | United States | 32501 |
23 | Sarasota Memorial Hospital | Sarasota | Florida | United States | 34239 |
24 | Grady Clinical Research Center | Atlanta | Georgia | United States | 30303 |
25 | Augusta University | Augusta | Georgia | United States | 30912 |
26 | Columbus Regional Research Institute | Columbus | Georgia | United States | 31904 |
27 | Cardiovascular Group PC | Lawrenceville | Georgia | United States | 30046 |
28 | Meridian Clinical Research, LLC | Savannah | Georgia | United States | 31406 |
29 | Northwest Heart Clinical Research, LLC | Arlington Heights | Illinois | United States | 60005 |
30 | University of Chicago | Chicago | Illinois | United States | 60637 |
31 | Captain James A. Lovell Federal Health Care Center | North Chicago | Illinois | United States | 60064 |
32 | Rockford Cardiovascular Associates | Rockford | Illinois | United States | 61107 |
33 | Midwest Cardiovascular Research and Education Foundation | Elkhart | Indiana | United States | 46514 |
34 | St. Francis Medical Group-Indiana Heart Physicians, Inc | Indianapolis | Indiana | United States | 46237 |
35 | Reid Hospital | Richmond | Indiana | United States | 47374 |
36 | Beacon Medical Group Clinical Research | South Bend | Indiana | United States | 46601 |
37 | Research Integrity, LLC | Owensboro | Kentucky | United States | 42303 |
38 | Cambridge Medical Trials | Alexandria | Louisiana | United States | 71301 |
39 | Louisiana Heart Center | Covington | Louisiana | United States | 70433 |
40 | Clinical Trials of America, LLC | Monroe | Louisiana | United States | 71201 |
41 | Tulane University Hospital and Clinic | New Orleans | Louisiana | United States | 70112 |
42 | Anne Arundel Medical Center | Annapolis | Maryland | United States | 21401 |
43 | Johns Hopkins University Hospital School of Medicine | Baltimore | Maryland | United States | 21205 |
44 | MedStar Health Research Institute | Baltimore | Maryland | United States | 21237 |
45 | Metropolitan Cardiovascular Consultants | Beltsville | Maryland | United States | 20705 |
46 | Spectrum Clinical Research | Towson | Maryland | United States | 21204 |
47 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
48 | East Mountain Medical Associates, PC | Great Barrington | Massachusetts | United States | 01230 |
49 | Alpena General Hospital | Alpena | Michigan | United States | 49707 |
50 | Regions Hospital | Saint Paul | Minnesota | United States | 55101 |
51 | Saint Louis University | Saint Louis | Missouri | United States | 63110 |
52 | SLHV | Saint Louis | Missouri | United States | 63136 |
53 | Palm Research Center | Las Vegas | Nevada | United States | 89148 |
54 | Advanced Heart Care, LLC | Bridgewater | New Jersey | United States | 08807 |
55 | Cardiac Care and Vascular Medicine, PLLC | Bronx | New York | United States | 10469 |
56 | Trinity Medical WNY, PC | Cheektowaga | New York | United States | 14227 |
57 | Northwell Health | Great Neck | New York | United States | 11021 |
58 | Mount Sinai School of Medicine | Lake Success | New York | United States | 11041 |
59 | St. Luke's Roosevelt Hospital | New York | New York | United States | 10025 |
60 | Harlem Cardiology | New York | New York | United States | 10035 |
61 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
62 | Asheville Cardiology Associates | Asheville | North Carolina | United States | 28803 |
63 | Kernodle Clinic West | Burlington | North Carolina | United States | 27215 |
64 | The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599-5021 |
65 | Novant Health Heart and Vascular Institute | Charlotte | North Carolina | United States | 28204 |
66 | Duke University Medical Center | Durham | North Carolina | United States | 27609 |
67 | Clinical Research of Gastonia | Gastonia | North Carolina | United States | 28054 |
68 | Clinical Trials of America, Inc | Lenoir | North Carolina | United States | 28645 |
69 | Rama Research LLC | Marion | Ohio | United States | 43302 |
70 | University of Toledo | Toledo | Ohio | United States | 43614 |
71 | South Oklahoma Heart Research Group | Oklahoma City | Oklahoma | United States | 73135 |
72 | Doylestown Health Cardiology | Doylestown | Pennsylvania | United States | 18901 |
73 | York Hospital, WellSpan Health | York | Pennsylvania | United States | 17403 |
74 | AnMed Health Clinical Research | Anderson | South Carolina | United States | 29621 |
75 | Ralph H. Johnson VA Medical Center | Charleston | South Carolina | United States | 29401 |
76 | Palmetto Health | Columbia | South Carolina | United States | 29203 |
77 | William Jennings Bryan Dorn VA Medical Center | Columbia | South Carolina | United States | 29209 |
78 | Clinical Research of Rock Hill | Rock Hill | South Carolina | United States | 29732 |
79 | Palmetto Research Center, LLC | Spartanburg | South Carolina | United States | 29302 |
80 | Methodist University Hospital | Memphis | Tennessee | United States | 38104 |
81 | Baylor Heart and Vascular Hospital | Dallas | Texas | United States | 75226 |
82 | Soltero Cardiovascular Research Center | Dallas | Texas | United States | 75226 |
83 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390-8837 |
84 | University of North Texas Health Science Center | Fort Worth | Texas | United States | 76107 |
85 | The Methodist Hospital | Houston | Texas | United States | 77030 |
86 | The Heart Hospital | Plano | Texas | United States | 75093 |
87 | Alpine Research Organization | Farmington | Utah | United States | 84025 |
88 | Cardiac Health Management Network, P.C. | Chester | Virginia | United States | 23836 |
89 | Hunter Holmes McGuire VA Medical Center | Richmond | Virginia | United States | 23249 |
90 | Roanoke Heart Institute PLC | Roanoke | Virginia | United States | 24014 |
91 | Salem VA Medical Center | Salem | Virginia | United States | 24153 |
92 | Marshfield Clinic | Marshfield | Wisconsin | United States | 54449 |
93 | Hospital Interzonal General de Agudos Dr Jose Penna | Bahia Blanca | Argentina | B8001DDU | |
94 | Hospital Italiano Regional del Sur, Bahia Blanca | Bahia Blanca | Argentina | B8001HXM | |
95 | CIPREC | Caba | Argentina | C1119ACN | |
96 | Hospital Italiano de Buenos Aires | Caba | Argentina | C1199ABB | |
97 | Consultorios Asociados de Endocrinología e Invest Clínica | Ciudad Autonoma Buenos Aires | Argentina | C1425AGC | |
98 | Instituto Cardiovascular de Buenos Aires | Ciudad Autonoma Buenos Aires | Argentina | C1428ART | |
99 | CCBR - Buenos Aires - AR | Ciudad Autonoma Buenos Aires | Argentina | C1430CKE | |
100 | Centro Médico Viamonte | Ciudad Autonoma de Bs As | Argentina | C1120AAC | |
101 | Sanatorio Güemes | Ciudad Autónoma de Bs As | Argentina | C1180AAX | |
102 | Instituto Medico Elsa Perez SRL (IMEP) | Ciudadela | Argentina | 1702 | |
103 | Clínica Colombo | Cordoba | Argentina | X5002AOQ | |
104 | Instituto Médico DAMIC S.R.L. | Cordoba | Argentina | X5003DCE | |
105 | Clinica Coronel Suarez SA | Coronel Suarez | Argentina | B7540DOL | |
106 | Instituto de Cardiología de Corrientes | Corrientes | Argentina | W3400AMZ | |
107 | Sanatorio Mayo Privado SA | Córdoba | Argentina | 5000 | |
108 | Centro de Investigaciones Clinicas Instituto del Corazon | Córdoba | Argentina | X5000EVQ | |
109 | Sanatorio Allende S.A. | Córdoba | Argentina | X5000JHQ | |
110 | Hospital Privado | Córdoba | Argentina | X5016KEH | |
111 | Hospital Italiano de La Plata | La Plata | Argentina | B1900AXI | |
112 | Centro de Investigaciones Médicas | Mar del Plata | Argentina | B7600FYK | |
113 | Hospital Privado de Comunidad | Mar del Plata | Argentina | B7602CBM | |
114 | Clínica Olivos | Olivos | Argentina | 1602 | |
115 | CER Instituto Médico | Quilmes | Argentina | B1878DVB | |
116 | Instituto de Investigaciones Clínicas de Quilmes | Quilmes | Argentina | B1878GEG | |
117 | Instituto de Investigaciones Clinicas de Rosario | Rosario | Argentina | 2000 | |
118 | Instituto Medico Fundación Grupo Colaborativo Rosario | Rosario | Argentina | 2000 | |
119 | Sanatorio Británico | Rosario | Argentina | 2000 | |
120 | Sanatorio Plaza | Rosario | Argentina | 2000 | |
121 | Sanatorio Parque | Rosario | Argentina | S2000DSV | |
122 | Instituto CAICI | Rosario | Argentina | S2000PBJ | |
123 | CORDIS S.A., Salta | Salta | Argentina | A4400ANW | |
124 | Centro Cardiovascular Salta | Salta | Argentina | A4406BFP | |
125 | Corporacion Medica de Gral. San Martin S.A. | San Martin | Argentina | B1650CSQ | |
126 | Investigaciones Clinicas Tucuman | San Miguel de Tucumán | Argentina | T4000ICL | |
127 | CCBR Tucuman | San Miguel de Tucumán | Argentina | T4000 | |
128 | Centro Medico Luquez | San Vicente | Argentina | X5006CBI | |
129 | Centro de Investigaciones Clínicas del Litoral | Santa Fe | Argentina | S3000FWO | |
130 | Hospital "Dr. José Maria Cullen " | Santa Fé | Argentina | S3000EOZ | |
131 | Instituto de Cardiología | Tucumán | Argentina | T4000JCU | |
132 | CEMEDIC - Centro de Especialidades Medicas | Villa Luro | Argentina | C1440CFD | |
133 | John Hunter Hospital | New Lambton Heights | New South Wales | Australia | 2305 |
134 | CORE Research Group | Milton | Queensland | Australia | 4064 |
135 | Mater Hospital Brisbane | South Brisbane | Queensland | Australia | 4101 |
136 | SA-Heart Ashford Specialist Centre | Ashford | South Australia | Australia | 5035 |
137 | Heart and Vascular Research | Fullarton | South Australia | Australia | 5063 |
138 | The Northern Hospital | Epping | Victoria | Australia | 3076 |
139 | St Vincent's Hospital Melbourne | Fitzroy | Victoria | Australia | 3065 |
140 | University Hospital Geelong | Geelong | Victoria | Australia | 3220 |
141 | Royal Melbourne Hospital | Parkville | Victoria | Australia | 3050 |
142 | AZ Sint-Jan Brugge | Brugge | Belgium | 3000 | |
143 | C.H.U. de Charleroi | Charleroi | Belgium | 6000 | |
144 | AZ Sint-Blasius | Dendermonde | Belgium | 9200 | |
145 | Ziekenhuis Oost-Limburg - Campus Sint-Jan | Genk | Belgium | 3600 | |
146 | AZ Sint-Lucas - Campus Sint Lucas | Gent | Belgium | 9000 | |
147 | Grand Hôpital de Charleroi | Gilly | Belgium | 6060 | |
148 | Jessa Ziekenhuis - Campus Virga Jesse | Hasselt | Belgium | 3500 | |
149 | La Louvière - UNIV CHU Tivoli | La Louvière | Belgium | 7100 | |
150 | UZ Leuven | Leuven | Belgium | 3000 | |
151 | AZ Sint-Maarten | Mechelen | Belgium | 2800 | |
152 | Hospital Felicio Rocho | Belo Horizonte | Brazil | 30110-060 | |
153 | Hospital Vera Cruz | Belo Horizonte | Brazil | 30140-062 | |
154 | Cardresearch Cardiologia Assistencial e de Pesquisas Ltda | Belo Horizonte | Brazil | 30150-240 | |
155 | CCBR - Brasília | Brasília | Brazil | 70200-730 | |
156 | ICDF - Instituto de Cardiologia do Distrito Federal | Brasília | Brazil | 70673-900 | |
157 | CECAP - Centro de Cardiologia Clínica | Brasília | Brazil | 70710-100 | |
158 | Hospital Angelina Caron | Campina Grande do Sul | Brazil | 83430-000 | |
159 | Centro Especializado em Cardiol Loema Instituto de Pesq Clin | Campinas | Brazil | 13010-001 | |
160 | IPECC - Instituto de Pesquisa Clínica de Campinas | Campinas | Brazil | 13060-080 | |
161 | CAEP - Centro Avançado de Estudos e Pesquisas Ltda.,Campinas | Campinas | Brazil | 13087-567 | |
162 | Hospital Universitário | Canoas | Brazil | 92425-900 | |
163 | IPCEM - Instituto de Pesquisa Clínica para Estudos Multicêntricos - Universidade de Caxias do Sul | Caxias do Sul | Brazil | 95070-560 | |
164 | Irmandade da Santa Casa de Misericórdia de Curitiba | Curitiba | Brazil | 80230-130 | |
165 | Hospital de Messejana Dr. Carlos Alberto Studart Gomes | Fortaleza | Brazil | 60846-190 | |
166 | Barroso e Sebba Ltda | Goiania | Brazil | 74223-130 | |
167 | HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás | Goiânia | Brazil | 74605-020 | |
168 | ICM - Instituto do Coracao de Marilia | Marília | Brazil | 17515-000 | |
169 | Hospital São Vicente de Paulo | Passo Fundo | Brazil | 99010-080 | |
170 | Santa Casa de Misericórdia de Porto Alegre | Porto Alegre | Brazil | 90035-074 | |
171 | Centro de Pesquisas em Diabetes | Porto Alegre | Brazil | 90035-170 | |
172 | Hospital de Clínicas de Porto Alegre | Porto Alegre | Brazil | 90035-903 | |
173 | Instituto de Cardiologia Rio Grande do Sul | Porto Alegre | Brazil | 90620-001 | |
174 | Hospital Agamenon Magalhaes | Recife | Brazil | 52051-380 | |
175 | H.C.da Fac. de Medicina de Ribeirao Preto | Ribeirão Preto | Brazil | 14048-900 | |
176 | Hospital Universitário Pedro Ernesto UERJ | Rio De Janeiro - RJ | Brazil | CEP 20551 | |
177 | CCBR - Rio de Janeiro - BR | Rio de Janeiro | Brazil | 22271-100 | |
178 | Pesquisare | Santo André | Brazil | 09080-110 | |
179 | Praxis Pesquisa Médica | Santo André | Brazil | 09090-790 | |
180 | Fundacao Faculdade Regional de Medicina, Sao Jose | Sao Jose do Rio Preto | Brazil | 15090-000 | |
181 | Centro de Pesquisa Clinica - CPCLIN | Sao Paulo | Brazil | 01244-030 | |
182 | FGM - Clínica Paulista de Doenças Cardiovasculares | Sao Paulo | Brazil | 01323-000 | |
183 | CEPIC - Centro Paulista de Investigacao Clinica | Sao Paulo | Brazil | 04266-010 | |
184 | INCOR e Hospital das Clínicas da Universidade de São Paulo | Sao Paulo | Brazil | 05403-000 | |
185 | CEMEC - Centro Multidisciplinar de Estudos Clínicos | São Bernardo do Campo | Brazil | 09780-000 | |
186 | CDEC BRASIL - Centro de Desenvolvimento em Estudos Clínicos Brasil | São Paulo | Brazil | 04020-060 | |
187 | Dr. Consulta | São Paulo | Brazil | 04208-002 | |
188 | CEDOES - Diagnóstico e Pesquisa,Vitória | Vitória | Brazil | 29055-450 | |
189 | Santa Casa de Votuporanga | Votuporanga | Brazil | 15500-003 | |
190 | Royal Alexandra Hospital | Edmonton | Alberta | Canada | T5H 3V9 |
191 | Vancouver General Hospital | Vancouver | British Columbia | Canada | V5Z 1M9 |
192 | St. Paul's Hospital | Vancouver | British Columbia | Canada | V6Z 1Y6 |
193 | Victoria Heart Institute Foundation | Victoria | British Columbia | Canada | V8R 4R2 |
194 | St. Boniface General Hospital | Winnipeg | Manitoba | Canada | R2H 2A6 |
195 | G.A. Research Associates Ltd | Moncton | New Brunswick | Canada | E1G 1A7 |
196 | QEII Health Sciences Centre | Halifax | Nova Scotia | Canada | B3H 2Y9 |
197 | Brampton Cardio Pulmonary Clinic | Brampton | Ontario | Canada | L6W 2X7 |
198 | JBN Medical Diagnostic Services Inc. | Burlington | Ontario | Canada | L7M 4Y1 |
199 | Cambridge Cardiac Care Inc. | Cambridge | Ontario | Canada | N1R 6V6 |
200 | Curnew Medicine Professional Corporation | Hamilton | Ontario | Canada | L8L 0A9 |
201 | Hamilton General Hospital | Hamilton | Ontario | Canada | L8L 2X2 |
202 | Southlake Regional Health Centre | Newmarket | Ontario | Canada | L3Y 2P6 |
203 | M Heffernan Medicine Professional Corp. | Oakville | Ontario | Canada | L6K 3W7 |
204 | Kawartha Cardiology Clinical Trials | Peterborough | Ontario | Canada | K9J 0B2 |
205 | Heart Health Institute | Scarborough | Ontario | Canada | M1B 4Z8 |
206 | Scarborough Cardiology Research | Scarborough | Ontario | Canada | M1E 5E9 |
207 | Health Sciences North | Sudbury | Ontario | Canada | P3E 5J1 |
208 | Canadian Phase Onward Inc. | Toronto | Ontario | Canada | M3J 2C5 |
209 | North York Diagnostic and Cardiac Centre | Toronto | Ontario | Canada | M6B 1N6 |
210 | Diabetes Heart Research Centre | Toronto | Ontario | Canada | M6G 1M2 |
211 | Mohan Babapulle Medicine Professional Medicine | Waterloo | Ontario | Canada | N2T 0C1 |
212 | Dr. Louis C.H. Yao | York | Ontario | Canada | M9N 1W4 |
213 | ViaCar Recherche Clinique Inc | Greenfield Park | Quebec | Canada | J4V 2G8 |
214 | Centre de Dépistage et Recherche Cardiovasculaire Rive-Sud | Longeuil | Quebec | Canada | J4M 2X1 |
215 | Clinique Santé Cardio MC | Montreal | Quebec | Canada | H1T 3Y7 |
216 | Montreal General Hospital - McGill University Health Centre | Montreal | Quebec | Canada | H3G 1A4 |
217 | McGill University Health Centre (MUHC) | Montreal | Quebec | Canada | H4A 3J1 |
218 | Centre de sante et de services sociaux de Beauce | Saint George-de-Beauce | Quebec | Canada | G5Y 4T8 |
219 | IUCPQ (Laval University) | Quebec | Canada | G1V 4G5 | |
220 | Cardiovascular Institute and Fu Wai Hospital | Beijing | China | 100037 | |
221 | Beijing Friendship Hospital | Beijing | China | 100050 | |
222 | First Hospital of Jilin University | Changchun | China | 130021 | |
223 | Hunan Provincial People's Hospital | Changsha | China | 410005 | |
224 | 2nd Xiangya Hospital of Central South University | Changsha | China | 410011 | |
225 | The Third Hospital of Changsha | Changsha | China | 410015 | |
226 | Dongguan People's Hospital | Dongguan | China | 523059 | |
227 | The First Affiliated Hospital of Fujian Medical University | Fuzhou | China | 350005 | |
228 | The First Afiliated Hospital, Sun Yet-sen University | Guangzhou | China | 510080 | |
229 | Guangzhou First Municipal People's Hospital | Guangzhou | China | 510180 | |
230 | Haikou People's Hospital | Haikou | China | 570208 | |
231 | HaiNan Provincial People's Hospital | Haikou | China | 570311 | |
232 | The First Affiliated Hospital of Lanzhou University | Lanzhou | China | 730000 | |
233 | The Second Affiliated Hospital of Lanzhou Medical University | Lanzhou | China | 730030 | |
234 | The Affiliated Hospital of Southwest Medical University | Luzhou | China | 646099 | |
235 | Nanchang University Affiliated 3rd Hospital | Nanchang | China | 330008 | |
236 | First Hospital Affiliated with Nanjing Medical University | Nanjing | China | 210029 | |
237 | Huashan Hospital, Fudan University | Shanghai | China | 200040 | |
238 | General Hospital of Shenyang Military Region | Shenyang | China | 110015 | |
239 | Shengjing Hospital of China Medical University | Shenyang | China | 110072 | |
240 | Tianjin Union Medical Center Nankai University Affiliated Hospital | Tianjin | China | 300121 | |
241 | Tongji Hospital, Tongji University | Wuhan | China | 430030 | |
242 | Renmin Hospital of Wuhan University | Wuhan | China | 430060 | |
243 | First Affiliated Hospital of Xi'an JiaoTong University | Xi'an | China | 710061 | |
244 | Yanbian University Hospital | Yanji | China | 133000 | |
245 | the first people hospital of Yue Yang | Yueyang | China | 414000 | |
246 | Affiliated Hospital of Jiangsu University | Zhenjiang | China | 212013 | |
247 | Poliklinika Humanitas | Bilovec | Czechia | 74301 | |
248 | Medicus Services Ltd. | Brandys Nad | Czechia | 250 01 | |
249 | Internal and Cardiology Practice, MUDr. Karel Kamenik, Brno | Brno | Czechia | 603 00 | |
250 | MUDr. Alexandra Ludkova | Brno | Czechia | 615 00 | |
251 | Vojenska nemocnice Brno | Brno | Czechia | 63600 | |
252 | Nemocnice Milosrdnych bratri | Brno | Czechia | 63900 | |
253 | Edumed s.r.o | Broumov | Czechia | 55001 | |
254 | MUDr. Jan Hubac, s.r.o. Kardiologicka ambulance | Chrudim | Czechia | 53702 | |
255 | Nemocnice ve Frydku-Mistku, prispevkova organizace | Frydek-Mistek | Czechia | 73818 | |
256 | MUDr. Ladislav Busak | Louny | Czechia | 440 01 | |
257 | Zdenek Vomacka | Olomouc | Czechia | 779 00 | |
258 | PV-Kardiologie s.r.o. | Pardubice | Czechia | 53002 | |
259 | University Hospital Motol | Prag 5 | Czechia | 15006 | |
260 | General Faculty Hospital, Prague | Prague 2 | Czechia | 128 08 | |
261 | Thomayer Hospital | Praha 4 - Krc | Czechia | 140 59 | |
262 | Kardio Vaclavik s.r.o. | Prerov | Czechia | 75000 | |
263 | Clinic of Cardiology, Pribram | Pribram | Czechia | 261 01 | |
264 | Hospital Trebic, p.o. | Trebic | Czechia | 67401 | |
265 | Masaryk Hospital, Usti nad Labem | Usti nad Labem | Czechia | 40113 | |
266 | Angiocor s.r.o | Zlin | Czechia | 76001 | |
267 | KIGE s.r.o | Znojmo | Czechia | 66902 | |
268 | HOP de Bayonne | Bayonne | France | 64100 | |
269 | HOP Jean Minjoz | Besançon | France | 25030 | |
270 | HOP Louis Pradel | Bron | France | 69500 | |
271 | HOP Côte de Nacre | Caen | France | 14033 | |
272 | HOP Arnaud de Villeneuve | Montpellier | France | 34295 | |
273 | HOP La Pitié Salpêtrière | Paris | France | 75651 | |
274 | Centre Hospitalier de Pau | Pau | France | 64046 | |
275 | HOP Haut-Lévêque | Pessac | France | 33600 | |
276 | HOP Rangueil | Toulouse | France | 31059 | |
277 | INS Louis Mathieu | Vandoeuvre-lès-Nancy | France | 54511 | |
278 | Universitätsklinikum Aachen, AöR | Aachen | Germany | 52074 | |
279 | Praxis Dr. Rieker, Berlin | Berlin | Germany | 10789 | |
280 | Charité - Universitätsmedizin Berlin | Berlin | Germany | 12200 | |
281 | Vivantes Netzwerk für Gesundheit GmbH | Berlin | Germany | 12351 | |
282 | Charité - Universitätsmedizin Berlin | Berlin | Germany | 13353 | |
283 | Klinikum Bielefeld gGmbH | Bielefeld | Germany | 33604 | |
284 | Praxis Dr. Menzel | Dessau-Roßlau | Germany | 06846 | |
285 | St. Johannes Hospital Dortmund | Dortmund | Germany | 44137 | |
286 | Städtisches Klinikum Dresden | Dresden | Germany | 01067 | |
287 | GWT-TUD GmbH | Dresden | Germany | 01307 | |
288 | Helios Klinikum Erfurt | Erfurt | Germany | 99089 | |
289 | Studienzentrum Bocholderstraße | Essen | Germany | 45355 | |
290 | ClinPhenomics GmbH & Co KG, Frankfurt | Frankfurt | Germany | 60594 | |
291 | Universitätsmedizin Göttingen, Georg-August-Universität | Göttingen | Germany | 37075 | |
292 | Asklepios Klinik St. Georg | Hamburg | Germany | 20099 | |
293 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
294 | Universitätsklinikum Heidelberg | Heidelberg | Germany | 69120 | |
295 | Universitätsklinikum des Saarlandes | Homburg | Germany | 66421 | |
296 | Universitätsklinikum Jena | Jena | Germany | 07740 | |
297 | Universitätsklinikum Schleswig-Holstein, Campus Kiel | Kiel | Germany | 24105 | |
298 | Asklepios Klinik Langen-Seligenstadt GmbH | Langen | Germany | 63225 | |
299 | Märkische Gesundheitsholding GmbH & Co. KG, Klinikum Lüdenscheid | Lüdenscheid | Germany | 58515 | |
300 | Praxis Dr. Sarnighausen, Lüneburg | Lüneburg | Germany | 21339 | |
301 | Katholisches Klinikum St. Hildegardiskrankenhaus, Mainz | Mainz | Germany | 55131 | |
302 | Deutsches Herzzentrum München | München | Germany | 80636 | |
303 | Kardiologische Gemeinschaftspraxis Nienburg | Nienburg | Germany | 31582 | |
304 | Kardiologische Praxis Papenburg | Papenburg | Germany | 26871 | |
305 | Universitätsklinikum Regensburg | Regensburg | Germany | 93053 | |
306 | Praxis Dr. Stenzel, Riesa | Riesa | Germany | 01587 | |
307 | Zentrum für Klinische Forschung | Wangen | Germany | 88239 | |
308 | Josephs-Hospital Warendorf | Warendorf | Germany | 48231 | |
309 | Petrus-Krankenhaus | Wuppertal | Germany | 42283 | |
310 | Lausmed Kft. Outpatient Unit of Internal Medicine | Baja | Hungary | 6500 | |
311 | Belgyogyaszati es Kardiologiai Maganrendelo | Bekescsaba | Hungary | 5600 | |
312 | Clinexpert Kft. | Budapest | Hungary | 1033 | |
313 | Gottsegen Gyorgy Hungarian Instit.of Cardiology,Budapest | Budapest | Hungary | 1096 | |
314 | Bajcsy-Zsilinszky Hospital and Clinic | Budapest | Hungary | 1106 | |
315 | Semmelweis University | Budapest | Hungary | 1122 | |
316 | Milit.Hosp.-State Health Cent. | Budapest | Hungary | 1134 | |
317 | Uzsoki Street Hospital, Budapest | Budapest | Hungary | 1145 | |
318 | Nehezlegzes Ambulancia | Debrecen | Hungary | 4027 | |
319 | Bugat Pal Hospital, Gyongyos | Gyongyos | Hungary | 3200 | |
320 | Selye Janos Hospital Komarom | Komarom | Hungary | 2900 | |
321 | Dorottya Kanizsai Hospital | Nagykanizsa | Hungary | 8800 | |
322 | Dr. Nagy Laszlo Kardiologiai Maganrendeles | Oroshaza | Hungary | 5900 | |
323 | Da Vinci Maganklinika | Pecs | Hungary | 7635 | |
324 | Pecsi Tudomanyegyetem | Pécs | Hungary | 7623 | |
325 | Fejer County Saint George University Teaching Hospital | Szekesfehervar | Hungary | 8000 | |
326 | Veszpremi Sziv es Egeszseg Centrum | Veszprem | Hungary | 8200 | |
327 | Doctor Jivraj Mehta Smarak Health Foundation | Ahmedabad | India | 380007 | |
328 | Kamalnayan Bajaj Hospital | Aurangabad | India | 431 005 | |
329 | Narayana Institute of Cardiac Sciences | Bangalore | India | 560099 | |
330 | Rajarajeswari Medical College | Bengaluru | India | 560074 | |
331 | Madras Medical Mission, | Chennai | India | 600 037 | |
332 | Apollo Speciality Hospital | Chennai | India | 600035 | |
333 | Medanta-The Medicity | Gurgaon | India | 122001 | |
334 | B.M. Birla Heart research Centre | Kolkatta | India | 700027 | |
335 | Siddhi Hospital | Nashik | India | 422007 | |
336 | Vijan Cardiac and Critical Care Centre | Nasik | India | 422005 | |
337 | Batra Hospital and Medical Research Centre | New Delhi | India | 110 062 | |
338 | GB Pant Hospital | New Delhi | India | 110002 | |
339 | Fortis Escorts Heart Institute | New Delhi | India | 110025 | |
340 | Sir Gangaram Hospital | New Delhi | India | 110060 | |
341 | Azienda Ospedaliera G. Rummo | Benevento | Italy | 82100 | |
342 | ASST Papa Giovanni XXIII - A.O. Papa Giovanni XXIII | Bergamo | Italy | 24127 | |
343 | Azienda Ospedaliera Universitaria Arcispedale Sant'Anna | Cona (FE) | Italy | 44124 | |
344 | Ospedale della Val di Chiana Santa Margherita | Cortona (AR) | Italy | 52040 | |
345 | Centro Cardiologico Monzino-IRCCS | Milano | Italy | 20138 | |
346 | Azienda Ospedaliera Universitaria "Federico II" | Napoli | Italy | 80131 | |
347 | Azienda Ospedaliera Universitaria Pisana | Pisa | Italy | 56126 | |
348 | Umberto I Pol. di Roma-Università di Roma La Sapienza | Roma | Italy | 00161 | |
349 | Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza | Roma | Italy | 00189 | |
350 | Azienda Servizi Sanitari 1 Triestina | Trieste | Italy | 34128 | |
351 | Kasugai Municipal Hospital | Aichi, Kasugai | Japan | 486-8510 | |
352 | Nagoya Kyoritsu Hospital | Aichi, Nagoya | Japan | 454-0933 | |
353 | Japanese Red Cross Nagoya Daini Hospital | Aichi, Nagoya | Japan | 466-8650 | |
354 | Toyota Memorial Hospital | Aichi, Toyota | Japan | 471-8513 | |
355 | Chiba Heart Clinic | Chiba, Chiba | Japan | 263-0043 | |
356 | Kimitsu Chuo Hospital | Chiba, Kisarazu | Japan | 292-8535 | |
357 | Seikeikai New Tokyo Heart Clinic | Chiba, Matsudo | Japan | 271-0077 | |
358 | Ehime Prefectural Central Hospital | Ehime, Matsuyama | Japan | 790-0024 | |
359 | Matsuyama Shimin Hospital | Ehime, Matsuyama | Japan | 790-0067 | |
360 | Uwajima City Hospital | Ehime, Uwajima | Japan | 798-8510 | |
361 | Fukuiken Saiseikai Hospital | Fukui, Fukui | Japan | 918-8503 | |
362 | Fukuoka University Chikushi Hospital | Fukuoka, Chikushino | Japan | 818-8502 | |
363 | Fukuokaken Saiseikai Futsukaichi Hospital | Fukuoka, Chikushino | Japan | 818-8516 | |
364 | Saiseikai Fukuoka General Hospital | Fukuoka, Fukuoka | Japan | 810-0001 | |
365 | National Hospital Organization Kyushu Medical Center | Fukuoka, Fukuoka | Japan | 810-8563 | |
366 | Kyushu University Hospital | Fukuoka, Fukuoka | Japan | 812-8582 | |
367 | Aso Co.,Ltd Iizuka Hospital | Fukuoka, Iizuka | Japan | 820-8505 | |
368 | Steel Memorial Yawata Hospital | Fukuoka, Kitakyushu | Japan | 805-8508 | |
369 | Japan Community Health Care Organization Kyushu Hospital | Fukuoka, Kitakyushu | Japan | 806-8501 | |
370 | Ogaki Municipal Hospital | Gifu, Ogaki | Japan | 503-8502 | |
371 | Chuno Kosei Hospital | Gifu, Seki | Japan | 501-3802 | |
372 | Fukuyama City Hospital | Hiroshima, Fukuyama | Japan | 721-8511 | |
373 | JA Hiroshima General Hospital | Hiroshima, Hatsukaichi | Japan | 738-8503 | |
374 | Shobara Red Cross Hospital | Hiroshima, Shobara | Japan | 727-0013 | |
375 | National Hospital Organization Hakodate Hospital | Hokkaido, Hakodate | Japan | 041-8512 | |
376 | Teine Keijinkai Clinic | Hokkaido, Sapporo | Japan | 006-0811 | |
377 | Tomakomai City Hospital | Hokkaido, Tomakomai | Japan | 053-8567 | |
378 | Hyogo Prefectural Amagasaki General Medical Center | Hyogo, Amagasaki | Japan | 660-8550 | |
379 | Hyogo Brain and Heart Center | Hyogo, Himeji | Japan | 670-0981 | |
380 | National Hospital Organization Kobe Medical Center | Hyogo, Kobe | Japan | 654-0155 | |
381 | Mito Medical Center | Ibaraki, Higashiibaraki-gun | Japan | 311-3193 | |
382 | National Hospital Organization Kanazawa Medical Center | Ishikawa, Kanazawa | Japan | 920-8650 | |
383 | Mitoyo General Hospital | Kagawa, Kanonji | Japan | 769-1695 | |
384 | Kagawa Prefectural Central Hospital | Kagawa, Takamatsu | Japan | 760-8557 | |
385 | Yamamoto Clinic | Kanagawa, Sagamihara | Japan | 252-0311 | |
386 | Kanagawa Cardiovascular and Respiratory Center | Kanagawa, Yokohama | Japan | 236-0051 | |
387 | Japanese Red Cross Kumamoto Hospital | Kumamoto, Kumamoto | Japan | 861-8520 | |
388 | Seiwakai Suizenji Touya Hospital | Kumamoto, Kumamoto | Japan | 862-0950 | |
389 | Kumamoto Rosai Hospital | Kumamoto, Yatsushiro | Japan | 866-8533 | |
390 | Uji-Tokushukai Medical Center | Kyoto, Uji | Japan | 611-0041 | |
391 | Sendai Kousei Hospital | Miyagi, Sendai | Japan | 980-0873 | |
392 | Sendai Tokushukai Hospital | Miyagi, Sendai | Japan | 981-3131 | |
393 | The Cardiovascular Center of Sendai | Miyagi, Sendai | Japan | 981-3133 | |
394 | National Hospital Organization Sendai Medical Center | Miyagi, Sendai | Japan | 983-8520 | |
395 | Miyazaki Medical Association Hospital | Miyazaki, Miyazaki | Japan | 880-0834 | |
396 | Hokushin General Hospital | Nagano, Nakano | Japan | 383-8505 | |
397 | Nagasaki Medical Center | Nagasaki, Omura | Japan | 856-8562 | |
398 | Okayama City General Medical Center | Okayama, Okayama | Japan | 700-8557 | |
399 | Naha City Hospital | Okinawa, Naha | Japan | 902-8511 | |
400 | Nanbu Tokushukai Hospital | Okinawa, Shimajiri-gun | Japan | 901-0493 | |
401 | Urasoe General Hospital | Okinawa, Urasoe | Japan | 901-2132 | |
402 | Higashiosaka City Medical Center | Osaka, Higashiosaka | Japan | 578-8588 | |
403 | Kitano Hospital | Osaka, Osaka | Japan | 530-8480 | |
404 | Yodogawa Christian Hospital | Osaka, Osaka | Japan | 533-0024 | |
405 | Seichokai Bell Land General Hospital | Osaka, Sakai | Japan | 599-8247 | |
406 | Hokusetsu General Hospital | Osaka, Takatsuki | Japan | 569-8585 | |
407 | San-Ai Hospital | Saitama, Saitama | Japan | 338-0837 | |
408 | Kosekai Iwatsuki-minami Hospital | Saitama, Saitama | Japan | 339-0033 | |
409 | Kusatsu General Hospital | Shiga, Kusatsu | Japan | 525-8585 | |
410 | Tokushima Prefectural Central Hospital | Tokushima, Tokushima | Japan | 770-8539 | |
411 | National Hospital Organization Tokyo Medical Center | Tokyo, Meguro-ku | Japan | 152-8902 | |
412 | Ome Municipal General Hospital | Tokyo, Ome | Japan | 198-0042 | |
413 | Tokyo Rosai Hospital | Tokyo, Ota-ku | Japan | 143-0013 | |
414 | Sekino Hospital | Tokyo, Toshima-ku | Japan | 171-0014 | |
415 | Minami Wakayama Medical Center | Wakayama, Tanabe | Japan | 646-8558 | |
416 | Kanmon Medical Center | Yamaguchi, Shimonoseki | Japan | 752-8510 | |
417 | Dong-A University Hospital | Busan | Korea, Republic of | 602-715 | |
418 | Inje University Busan Paik Hospital | Busan | Korea, Republic of | 614-735 | |
419 | Chungbuk National University Hospital | Cheongju | Korea, Republic of | 361-771 | |
420 | Chungnam National University Hospital | Daejeon | Korea, Republic of | 35015 | |
421 | Gachon University Gil Medical Center | Incheon | Korea, Republic of | 21565 | |
422 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
423 | Severance Hospital | Seoul | Korea, Republic of | 03722 | |
424 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
425 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
426 | Korea University Guro Hospital | Seoul | Korea, Republic of | 08308 | |
427 | Seoul National University Bundang Hospital | Sungnam | Korea, Republic of | 463-707 | |
428 | Wonju Severance Christian Hosp | Wonju | Korea, Republic of | 26426 | |
429 | Hospital Cardiologica Aguascalientes | Aguascalientes | Mexico | 20230 | |
430 | Instituto Nacional de Cardiologia Ignacio Chavez | Ciudad de Mexico | Mexico | 14080 | |
431 | Centro de Investigacion Biomedica y Farmaceutica, S.C. | Distrito Federal | Mexico | 03100 | |
432 | Unidad de Investigacion Clinica Cardiometabolica de Occident | Guadalajara | Mexico | 44150 | |
433 | Diseño y Planeación en Investigación Médica SC | Guadalajara | Mexico | 44656 | |
434 | Cardiologia Clinica e Intervencionista | Guadalajara | Mexico | 44670 | |
435 | Centro de Investigación Clinica Acelerada, S.C. | Mexico | Mexico | 07020 | |
436 | Instituto Cardiovascular de Monclova, S de RL de CV | Monclova | Mexico | 25750 | |
437 | CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc | México | Mexico | 11650 | |
438 | Hospital Universitario Dr Jose Eleuterio Gonzalez | Nuevo Leon | Mexico | 64460 | |
439 | Centro Integral Medico SJR S.C. | San Juan del Rio | Mexico | 76800 | |
440 | Cardioarritmias e Investigación S.C | San Luis Potosi | Mexico | 78213 | |
441 | Centro de Investigacion Cardiovascular y Metabolica | Tijuana | Mexico | 22500 | |
442 | Centro de Investigacion Medica Alberto Bazzoni S.A. de C.V. | Torreon | Mexico | 27000 | |
443 | Hospital Dr Angel Leano | Zapopan | Mexico | 45200 | |
444 | Ziekenhuisgroep Twente locatie Almelo | Almelo | Netherlands | 7609 PP | |
445 | BovenIJ Ziekenhuis | Amsterdam | Netherlands | 1034 CS | |
446 | Onze Lieve Vrouwe Gasthuis, Locatie West | Amsterdam | Netherlands | 1061 AE | |
447 | Amsterdam UMC Locatie VUMC | Amsterdam | Netherlands | 1081HV | |
448 | Onze Lieve Vrouwe Gasthuis | Amsterdam | Netherlands | 1091AC | |
449 | Amsterdam UMC, Locatie AMC | Amsterdam | Netherlands | 1105 AZ | |
450 | Rode Kruis Ziekenhuis Beverwijk | Beverwijk | Netherlands | 1942 LE | |
451 | Tergooiziekenhuizen locatie Blaricum | Blaricum | Netherlands | 1261 AN | |
452 | Amphia Ziekenhuis | Breda | Netherlands | 4818 CK | |
453 | HMC Bronovo | Den Haag | Netherlands | 2597 AX | |
454 | Ziekenhuis Gelderse Vallei | EDE | Netherlands | 6716 RP | |
455 | Catharina Ziekenhuis | Eindhoven | Netherlands | 5623 EJ | |
456 | Universitair Medisch Centrum Groningen | Groningen | Netherlands | 9713 GZ | |
457 | Zuyderland Medisch Centrum | Heerlen | Netherlands | 6419 PC | |
458 | Vasculair Onderzoek Centrum | Hoorn | Netherlands | 1624 NP | |
459 | Maastricht Universitair Medisch Centrum | Maastricht | Netherlands | 6229 HX | |
460 | Diaconessenhuis Meppel | Meppel | Netherlands | 7943 KA | |
461 | St. Antonius ziekenhuis, locatie Nieuwegein | Nieuwegein | Netherlands | 3435 CM | |
462 | Radboud Universitair Medisch Centrum | Nijmegen | Netherlands | 6525 GL | |
463 | Ziekenhuis Bernhoven Uden | Uden | Netherlands | 5406 PT | |
464 | Vie Curi Medisch Centrum | Venlo | Netherlands | 5912 BL | |
465 | De Heel - Zaans Medisch Centrum | Zaandam | Netherlands | 1502 DV | |
466 | Gelre Ziekenhuis Zutphen | Zutphen | Netherlands | 7207 AE | |
467 | KLIMED Marek Klimkiewicz | Bialystok | Poland | 15-765 | |
468 | Univ. Clinic Hosp, Bialystok | Bialystok | Poland | 15276 | |
469 | American Heart of Poland Sp. z o.o. | Bielsko-Biala | Poland | 43-316 | |
470 | NZOZ Centrum Medyczne KERmed | Bydgoszcz | Poland | 85231 | |
471 | Polsko-Amerykanskie Kliniki Serca | Chorzow | Poland | 32-500 | |
472 | American Heart of Poland Sp. z o.o. | Dabrowa Gornicza | Poland | 41-300 | |
473 | Poradnia Kardiologiczna Jaroslaw Jurowiecki | Gdansk | Poland | 80-286 | |
474 | University Clinical Center, Gdansk | Gdansk | Poland | 80952 | |
475 | Indywidualna Specjalistyczna Praktyka Lekarska | Gdynia | Poland | 81-157 | |
476 | Saint Wincenty a Paulo Hosp., Cardiology Dept., Gdynia | Gdynia | Poland | 81348 | |
477 | Szpital Zakonu Bonifratow Sp. z o.o. | Katowice | Poland | 40-211 | |
478 | Specialistic Cardiology&Hypertension Out-patient Clin,Kielce | Kielce | Poland | 25525 | |
479 | Leszek Bryniarski Specialized Medical Cabinet | Krakow | Poland | 30-082 | |
480 | Krakow Specialistic Hospital of John Paul II | Krakow | Poland | 31-202 | |
481 | SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia | Lodz | Poland | 90-302 | |
482 | Nzoz Salus | Lodz | Poland | 91-302 | |
483 | Individual Specialized Practice | Lodz | Poland | 94-255 | |
484 | Lowickie Cardiology Center | Lowicz | Poland | 99-400 | |
485 | American Heart of Poland Sp. z o.o. | Nysa | Poland | 48-300 | |
486 | Medicome Sp. z o.o. | Oswiecim | Poland | 32-600 | |
487 | Specialized Practice Dr. Janusz Spyra | Ruda Slaska | Poland | 41-709 | |
488 | Centrum Medyczne Medyk | Rzeszow | Poland | 35-055 | |
489 | Lukmed Lukasz Wozniak | Siedlce | Poland | 08-110 | |
490 | Clinmedica Research Omc sp. z o.o. sp.k., Skierniewice | Skierniewice | Poland | 96-100 | |
491 | KO-MED Centra Kliniczne Staszow | Staszow | Poland | 28-200 | |
492 | The Provincial Polyclinical Hospital in Torun | Torun | Poland | 87-100 | |
493 | American Heart of Poland Sp. z o.o. | Tychy | Poland | 43-100 | |
494 | American Heart of Poland Sp. z o.o. | Ustron | Poland | 43-450 | |
495 | Central Hospital of Medical Academy, Warsaw | Warsaw | Poland | 02-097 | |
496 | McM Polimedica | Warszawa | Poland | 02-777 | |
497 | 4. Military Clinical Hospital with Polyclinic SP ZOZ | Wroclaw | Poland | 50-981 | |
498 | Zgierskie Center of Cardiology MED-PRO | Zgierz | Poland | 95-100 | |
499 | Specialist Hospital J. Dietla NZOZ Specialized Clinic "Gemini" | Zychlin | Poland | 62-571 | |
500 | Hospital Quiron. I.C.U. | Barcelona | Spain | 08023 | |
501 | Hospital Santa Creu i Sant Pau | Barcelona | Spain | 08026 | |
502 | Hospital Universitario Virgen de la Arrixaca | El Palmar | Spain | 30120 | |
503 | Hospital de Bellvitge | L'Hospitalet de Llobregat | Spain | 08907 | |
504 | Hospital Ramón y Cajal | Madrid | Spain | 28034 | |
505 | Hospital Clínico San Carlos | Madrid | Spain | 28040 | |
506 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
507 | Hospital La Paz | Madrid | Spain | 28046 | |
508 | Hospital Virgen de la Victoria | Malaga | Spain | 29010 | |
509 | Complejo Hospitalario Universitario de Orense | Orense | Spain | 32005 | |
510 | Hospital Clínico de Santiago | Santiago de Compostela | Spain | 15706 | |
511 | Hospital Clínico Universitario de Valladolid | Valladolid | Spain | 47003 | |
512 | Barnet General Hospital | Barnet | United Kingdom | EN5 3DJ | |
513 | University Hospital of Wales | Cardiff | United Kingdom | CF14 4XW | |
514 | Park & St Francis Surgery | Eastleigh | United Kingdom | SO53 4ST | |
515 | Wycombe General Hospital | High Wycombe | United Kingdom | HP11 2TT | |
516 | Glenfield Hospital | Leicester | United Kingdom | LE3 9QP | |
517 | St Bartholomew's Hospital | London | United Kingdom | EC1A 7BE | |
518 | Luton and Dunstable University Hospital | Luton | United Kingdom | LU4 0DZ | |
519 | St Mary's Hospital | Newport | United Kingdom | PO30 5TG | |
520 | Morriston Hospital | Swansea | United Kingdom | SA6 6NL |
Sponsors and Collaborators
- Boehringer Ingelheim
- Eli Lilly and Company
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 1245.121
- 2016-002280-34
Study Results
Participant Flow
Recruitment Details | A randomised, double-blind trial to demonstrate superiority of empagliflozin versus placebo, in patients with chronic Heart Failure with reduced Ejection Fraction (HFrEF). |
---|---|
Pre-assignment Detail | Patients were included in the trial after they had signed the informed consent form (ICF). All patients who met the all inclusion and none of the exclusion criteria during screening and at the randomisation approximately 1 to 4 weeks later were randomised to empagliflozin or placebo in a 1:1 ratio. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Period Title: Discontinuation From Treatment | ||
STARTED | 1867 | 1863 |
Treated | 1863 | 1863 |
COMPLETED | 1352 | 1381 |
NOT COMPLETED | 515 | 482 |
Period Title: Discontinuation From Treatment | ||
STARTED | 1867 | 1863 |
Treated | 1863 | 1863 |
COMPLETED | 1847 | 1841 |
NOT COMPLETED | 20 | 22 |
Baseline Characteristics
Arm/Group Title | Placebo | 10 mg Empagliflozin | Total |
---|---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. | Total of all reporting groups |
Overall Participants | 1867 | 1863 | 3730 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
66.5
(11.2)
|
67.2
(10.8)
|
66.8
(11.0)
|
Sex: Female, Male (Count of Participants) | |||
Female |
456
24.4%
|
437
23.5%
|
893
23.9%
|
Male |
1411
75.6%
|
1426
76.5%
|
2837
76.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
613
32.8%
|
616
33.1%
|
1229
32.9%
|
Not Hispanic or Latino |
1178
63.1%
|
1164
62.5%
|
2342
62.8%
|
Unknown or Not Reported |
76
4.1%
|
83
4.5%
|
159
4.3%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
24
1.3%
|
15
0.8%
|
39
1%
|
Asian |
335
17.9%
|
337
18.1%
|
672
18%
|
Native Hawaiian or Other Pacific Islander |
6
0.3%
|
8
0.4%
|
14
0.4%
|
Black or African American |
134
7.2%
|
123
6.6%
|
257
6.9%
|
White |
1304
69.8%
|
1325
71.1%
|
2629
70.5%
|
More than one race |
33
1.8%
|
28
1.5%
|
61
1.6%
|
Unknown or Not Reported |
31
1.7%
|
27
1.4%
|
58
1.6%
|
Outcome Measures
Title | Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) |
---|---|
Description | Time to the first event of adjudicated cardiovascular (CV) death or adjudicated hospitalisation for heart failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set: All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
21.00
|
15.77
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | Model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment. alpha = 0.0496 (resulting from interim analysis) eGFR (CKP-EPI)cr: Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement LVEF: Left ventricular ejection fraction. | |
Type of Statistical Test | Superiority | |
Comments | H0: There is no difference between the effect of placebo and the effect of empagliflozin. | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.75 | |
Confidence Interval |
(2-Sided) 95.04% 0.65 to 0.86 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. Placebo [T/P] |
Title | Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) |
---|---|
Description | Reported is the total number of HHF events (first and recurrent) which occurred. All data up to the end of the planned treatment period (including the data after the end of treatment for patients not completing the treatment period as planned) from all randomised patients was used. |
Time Frame | From randomisation until completion of the planned treatment phase, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set (RS): All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number [HHF events] |
553
|
388
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | Model accounts for dependence between recurrent HHF and cardiovascular death, with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment. eGFR (CKP-EPI)cr: Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement LVEF: Left ventricular ejection fraction. | |
Type of Statistical Test | Superiority | |
Comments | H0: There is no difference between the effect of placebo and the effect of empagliflozin. | |
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Joint frailty model | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.70 | |
Confidence Interval |
(2-Sided) 95.04% 0.58 to 0.85 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | HR vs placebo of recurrent HFF |
Title | eGFR (CKD-EPI) cr Slope of Change From Baseline |
---|---|
Description | Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) [mL/min/1.73m2] slope of change from baseline. Available on-treatment change-from-baseline data were to be used. Patients without on-treatment data after randomisation were not to be included in this analysis. Slope represents the long term effect on eGFR. Timepoints after baseline were included in calculation of slope of change from baseline. Descriptive statistic (mean(standard error)) is reported. |
Time Frame | Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Treated Set (TS): All patients treated with at least one dose of the study medication and at least one on-treatment measurement of eGFR. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1792 | 1799 |
Mean (Standard Error) [Milliliter/minute/1.73 meters squared] |
-2.278
(0.229)
|
-0.546
(0.227)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | Random coefficient model allowing for random intercept and random slope per patient, with the same factors used for the primary endpoint (age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment) and additional factors "time", "treatment-by-time interaction", and "baseline eGFR (CKD-EPI)cr-by-time interaction". Only "on-treatment" data from treated patients were used. alpha=0.001 | |
Type of Statistical Test | Superiority | |
Comments | H0: There is no difference between the effect of placebo and the effect of empagliflozin. | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Random intercept random coef. model | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment by time interaction |
Estimated Value | 1.733 | |
Confidence Interval |
(2-Sided) 99.9% 0.669 to 2.796 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Empa vs Placebo slope [/year] |
Title | Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr |
---|---|
Description | Time to the first event in the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), renal transplant, or sustained reduction in Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set: All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
3.07
|
1.56
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0019 |
Comments | ||
Method | Regression, Cox | |
Comments | Cox regression model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.50 | |
Confidence Interval |
(2-Sided) 95% 0.32 to 0.77 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. Placebo |
Title | Time to First Adjudicated Hospitalisation for Heart Failure (HHF) |
---|---|
Description | Time to first adjudicated Hospitalisation for Heart Failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set (RS): All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
15.55
|
10.75
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Regression, Cox | |
Comments | Cox regression model with terms for age, baseline eGFR (CKD-EPK)cr, region, baseline diabetes status, sex, baseline LVEF, and treatment. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.69 | |
Confidence Interval |
(2-Sided) 95% 0.59 to 0.81 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs Placebo |
Title | Time to Adjudicated Cardiovascular (CV) Death |
---|---|
Description | Time to adjudicated CV (Cardiovascular) death. The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set: All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
8.13
|
7.55
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4133 |
Comments | ||
Method | Regression, Cox | |
Comments | Model with terms for age, baseline eGFR (CKD-EPI), region, baseline diabetes status, sex, baseline LVEF and treatment. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.92 | |
Confidence Interval |
(2-Sided) 95% 0.75 to 1.12 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. Placebo |
Title | Time to All-cause Mortality |
---|---|
Description | Time to all-cause mortality. The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set: All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
10.71
|
10.06
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3536 |
Comments | ||
Method | Regression, Cox | |
Comments | Cox regression model with terms for age, baseline eGFR (CKD-EPI), region, baseline diabetes status, sex, baseline LVEF and treatment. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.92 | |
Confidence Interval |
(2-Sided) 95% 0.77 to 1.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. placebo |
Title | Time to Onset of Diabetes Mellitus (DM) |
---|---|
Description | Time to onset of DM (Glycated haemoglobin (HbA1c) ≥6.5% or as diagnosed by the investigator) in patients with pre-DM (no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of 5.7 to <6.5%). The incidence rate (patients with events per 100 person years at risk) is reported. The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: Sum of time at risk [days] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier. Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk. |
Time Frame | From randomisation until completion of the planned treatment period, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the randomised set with pre-DM. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 636 | 632 |
Number (95% Confidence Interval) [Patients with events/ 100 pt-yrs at risk] |
10.62
|
9.31
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3576 |
Comments | ||
Method | Regression, Cox | |
Comments | Cox regression model with terms for age, baseline eGFR (CDK-EPI), region, sex, baseline LVEF and treatment. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.86 | |
Confidence Interval |
(2-Sided) 95% 0.62 to 1.19 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. placebo |
Title | Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52 |
---|---|
Description | Change from baseline in KCCQ (Kansas City cardiomyopathy questionnaire) clinical summary score at Week 52. The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, selfefficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status. For patients who died, a worst score (score of 0) is imputed at all subsequent scheduled visits after the date of death. Standard error is adjusted standard error. Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported. |
Time Frame | Assessed at baseline, week 12, week 32 and week 52. |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the randomized set (RS) with available data for this endpoint, including values obtained on treatment or post-treatment. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1395 | 1401 |
Least Squares Mean (Standard Error) [Score on a scale] |
-3.36
(0.69)
|
-1.30
(0.69)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | Mixed model with age, baseline eGFR (CKD-EPI) as linear covariate(s) and region, baseline diabetes status, sex, baseline LVEF, week reachable, treatment by visit interaction, baseline KCCQ - Clinical Summary Score by Visit interaction as fixed effects. An unstructured covariance structure has been used. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0340 |
Comments | ||
Method | Mixed Model | |
Comments | Mixed model for repeated measures (MMRM) | |
Method of Estimation | Estimation Parameter | Difference of adjusted means |
Estimated Value | 2.06 | |
Confidence Interval |
(2-Sided) 95% 0.16 to 3.96 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
Estimation Comments | Comparison vs. placebo |
Title | Number of All-cause Hospitalizations (First and Recurrent) |
---|---|
Description | Number of all-cause hospitalizations (first and recurrent). |
Time Frame | From randomisation until completion of the planned treatment phase, up to 1040 days. |
Outcome Measure Data
Analysis Population Description |
---|
Randomised Set: All randomised patients. |
Arm/Group Title | Placebo | 10 mg Empagliflozin |
---|---|---|
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. |
Measure Participants | 1867 | 1863 |
Number [Hospitalizations for any cause] |
1570
|
1364
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg Empagliflozin |
---|---|---|
Comments | Joint frailty model with terms for age, baseline eGFR (CDK-EPI), region, sex, baseline diabetes status and baseline LVEF. Model accounts for dependence between recurrent all-cause hospitalizations and all-cause mortality. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0065 |
Comments | ||
Method | Joint frailty model | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.85 | |
Confidence Interval |
(2-Sided) 95% 0.75 to 0.95 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Comparison vs. placebo |
Adverse Events
Time Frame | From first intake of study medication until end of planned treatment period + 7 days (Residual Effect Period), up to 1047 days. | |||
---|---|---|---|---|
Adverse Event Reporting Description | [All-Cause Mortality]: Randomised Set: All randomised patients. [Serious Adverse Events and Other Adverse Events]: Treated Set: All patients treated with at least one dose of study drug. | |||
Arm/Group Title | Placebo | 10 mg Empagliflozin | ||
Arm/Group Description | 1 film-coated tablet of matching placebo was administered orally once daily. | Film-coated tablet of 10 milligram (mg) Empagliflozin was administered orally once daily. | ||
All Cause Mortality |
||||
Placebo | 10 mg Empagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 266/1867 (14.2%) | 249/1863 (13.4%) | ||
Serious Adverse Events |
||||
Placebo | 10 mg Empagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 896/1863 (48.1%) | 772/1863 (41.4%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 6/1863 (0.3%) | 10/1863 (0.5%) | ||
Blood loss anaemia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Disseminated intravascular coagulation | 0/1863 (0%) | 1/1863 (0.1%) | ||
Iron deficiency anaemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Leukocytosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pancytopenia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Splenic haematoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Splenic infarction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Thrombocytopenia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cardiac disorders | ||||
Acute coronary syndrome | 3/1863 (0.2%) | 0/1863 (0%) | ||
Acute left ventricular failure | 5/1863 (0.3%) | 7/1863 (0.4%) | ||
Acute myocardial infarction | 18/1863 (1%) | 24/1863 (1.3%) | ||
Angina pectoris | 10/1863 (0.5%) | 6/1863 (0.3%) | ||
Angina unstable | 9/1863 (0.5%) | 11/1863 (0.6%) | ||
Aortic valve stenosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Arrhythmia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Arrhythmia supraventricular | 0/1863 (0%) | 1/1863 (0.1%) | ||
Arteriosclerosis coronary artery | 2/1863 (0.1%) | 0/1863 (0%) | ||
Atrial fibrillation | 44/1863 (2.4%) | 24/1863 (1.3%) | ||
Atrial flutter | 11/1863 (0.6%) | 3/1863 (0.2%) | ||
Atrial tachycardia | 2/1863 (0.1%) | 4/1863 (0.2%) | ||
Atrial thrombosis | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Atrioventricular block complete | 1/1863 (0.1%) | 4/1863 (0.2%) | ||
Atrioventricular block second degree | 0/1863 (0%) | 1/1863 (0.1%) | ||
Bradyarrhythmia | 0/1863 (0%) | 2/1863 (0.1%) | ||
Bradycardia | 4/1863 (0.2%) | 0/1863 (0%) | ||
Bundle branch block left | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Cardiac aneurysm | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiac arrest | 10/1863 (0.5%) | 9/1863 (0.5%) | ||
Cardiac asthma | 0/1863 (0%) | 2/1863 (0.1%) | ||
Cardiac disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cardiac dysfunction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiac failure | 444/1863 (23.8%) | 332/1863 (17.8%) | ||
Cardiac failure acute | 29/1863 (1.6%) | 19/1863 (1%) | ||
Cardiac failure chronic | 32/1863 (1.7%) | 18/1863 (1%) | ||
Cardiac failure congestive | 41/1863 (2.2%) | 26/1863 (1.4%) | ||
Cardiac tamponade | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cardiac ventricular thrombosis | 2/1863 (0.1%) | 5/1863 (0.3%) | ||
Cardio-respiratory arrest | 4/1863 (0.2%) | 1/1863 (0.1%) | ||
Cardiogenic shock | 11/1863 (0.6%) | 8/1863 (0.4%) | ||
Cardiomegaly | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiomyopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiopulmonary failure | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Cardiorenal syndrome | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiovascular disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Chronic left ventricular failure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Congestive cardiomyopathy | 6/1863 (0.3%) | 1/1863 (0.1%) | ||
Coronary artery disease | 16/1863 (0.9%) | 2/1863 (0.1%) | ||
Coronary artery occlusion | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Coronary artery stenosis | 2/1863 (0.1%) | 3/1863 (0.2%) | ||
Coronary ostial stenosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Intracardiac thrombus | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Ischaemic cardiomyopathy | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Left ventricular dysfunction | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Left ventricular failure | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Low cardiac output syndrome | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Mitral valve incompetence | 5/1863 (0.3%) | 4/1863 (0.2%) | ||
Myocardial infarction | 16/1863 (0.9%) | 16/1863 (0.9%) | ||
Myocardial ischaemia | 1/1863 (0.1%) | 3/1863 (0.2%) | ||
Palpitations | 1/1863 (0.1%) | 0/1863 (0%) | ||
Paroxysmal atrioventricular block | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pericardial effusion | 0/1863 (0%) | 1/1863 (0.1%) | ||
Prinzmetal angina | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Pulseless electrical activity | 1/1863 (0.1%) | 0/1863 (0%) | ||
Right ventricular failure | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Supraventricular tachycardia | 6/1863 (0.3%) | 2/1863 (0.1%) | ||
Torsade de pointes | 0/1863 (0%) | 1/1863 (0.1%) | ||
Trifascicular block | 1/1863 (0.1%) | 0/1863 (0%) | ||
Ventricular arrhythmia | 5/1863 (0.3%) | 1/1863 (0.1%) | ||
Ventricular extrasystoles | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Ventricular fibrillation | 8/1863 (0.4%) | 10/1863 (0.5%) | ||
Ventricular flutter | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Ventricular tachyarrhythmia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Ventricular tachycardia | 37/1863 (2%) | 55/1863 (3%) | ||
Congenital, familial and genetic disorders | ||||
Dermoid cyst | 2/1863 (0.1%) | 0/1863 (0%) | ||
Gastrointestinal arteriovenous malformation | 0/1863 (0%) | 1/1863 (0.1%) | ||
Phimosis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Type IV hyperlipidaemia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Ear and labyrinth disorders | ||||
Deafness | 1/1863 (0.1%) | 0/1863 (0%) | ||
Deafness neurosensory | 1/1863 (0.1%) | 0/1863 (0%) | ||
Deafness unilateral | 0/1863 (0%) | 1/1863 (0.1%) | ||
Mixed deafness | 0/1863 (0%) | 1/1863 (0.1%) | ||
Sudden hearing loss | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vertigo | 0/1863 (0%) | 1/1863 (0.1%) | ||
Vertigo positional | 0/1863 (0%) | 1/1863 (0.1%) | ||
Endocrine disorders | ||||
Cushing's syndrome | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hyperthyroidism | 2/1863 (0.1%) | 3/1863 (0.2%) | ||
Hypothyroidism | 2/1863 (0.1%) | 0/1863 (0%) | ||
Eye disorders | ||||
Cataract | 3/1863 (0.2%) | 5/1863 (0.3%) | ||
Cataract cortical | 0/1863 (0%) | 1/1863 (0.1%) | ||
Diabetic retinopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Glaucoma | 5/1863 (0.3%) | 3/1863 (0.2%) | ||
Macular degeneration | 1/1863 (0.1%) | 0/1863 (0%) | ||
Open angle glaucoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Retinal detachment | 0/1863 (0%) | 3/1863 (0.2%) | ||
Retinal tear | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Vitreous haemorrhage | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Abdominal pain upper | 0/1863 (0%) | 2/1863 (0.1%) | ||
Abdominal wall haematoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Acute abdomen | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Chronic gastritis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Coeliac disease | 0/1863 (0%) | 1/1863 (0.1%) | ||
Colitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Colitis ischaemic | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Constipation | 1/1863 (0.1%) | 3/1863 (0.2%) | ||
Diarrhoea | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Duodenal ulcer | 0/1863 (0%) | 2/1863 (0.1%) | ||
Enteritis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Erosive oesophagitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gastric haemorrhage | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gastric mucosa erythema | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gastric perforation | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gastric ulcer | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gastritis | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Gastritis erosive | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Gastrointestinal haemorrhage | 4/1863 (0.2%) | 8/1863 (0.4%) | ||
Gastrointestinal necrosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gastrointestinal ulcer haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gastrointestinal vascular malformation haemorrhagic | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gingival bleeding | 1/1863 (0.1%) | 0/1863 (0%) | ||
Haematochezia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Haemorrhoids | 0/1863 (0%) | 2/1863 (0.1%) | ||
Ileus | 0/1863 (0%) | 1/1863 (0.1%) | ||
Ileus paralytic | 1/1863 (0.1%) | 0/1863 (0%) | ||
Incarcerated inguinal hernia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Inguinal hernia | 0/1863 (0%) | 7/1863 (0.4%) | ||
Intestinal ischaemia | 2/1863 (0.1%) | 0/1863 (0%) | ||
Intestinal obstruction | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Intussusception | 1/1863 (0.1%) | 0/1863 (0%) | ||
Large intestine polyp | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Mallory-Weiss syndrome | 0/1863 (0%) | 1/1863 (0.1%) | ||
Mechanical ileus | 0/1863 (0%) | 1/1863 (0.1%) | ||
Mesenteric artery stenosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Nausea | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Obstructive pancreatitis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Oesophageal obstruction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pancreatitis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Pancreatitis acute | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Pancreatitis chronic | 1/1863 (0.1%) | 0/1863 (0%) | ||
Periodontal disease | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pharyngo-oesophageal diverticulum | 0/1863 (0%) | 1/1863 (0.1%) | ||
Rectal haemorrhage | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Small intestinal obstruction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Upper gastrointestinal haemorrhage | 7/1863 (0.4%) | 5/1863 (0.3%) | ||
Vomiting | 1/1863 (0.1%) | 0/1863 (0%) | ||
General disorders | ||||
Cardiac death | 8/1863 (0.4%) | 4/1863 (0.2%) | ||
Chest pain | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Death | 27/1863 (1.4%) | 20/1863 (1.1%) | ||
Discomfort | 1/1863 (0.1%) | 0/1863 (0%) | ||
Euthanasia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Foreign body reaction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gait disturbance | 0/1863 (0%) | 1/1863 (0.1%) | ||
Implant site haematoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Medical device site haematoma | 2/1863 (0.1%) | 0/1863 (0%) | ||
Multiple organ dysfunction syndrome | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Non-cardiac chest pain | 7/1863 (0.4%) | 5/1863 (0.3%) | ||
Oedema due to cardiac disease | 0/1863 (0%) | 1/1863 (0.1%) | ||
Oedema peripheral | 2/1863 (0.1%) | 3/1863 (0.2%) | ||
Pyrexia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Stent-graft endoleak | 2/1863 (0.1%) | 0/1863 (0%) | ||
Sudden cardiac death | 10/1863 (0.5%) | 8/1863 (0.4%) | ||
Sudden death | 5/1863 (0.3%) | 5/1863 (0.3%) | ||
Systemic inflammatory response syndrome | 0/1863 (0%) | 1/1863 (0.1%) | ||
Vascular device occlusion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vessel puncture site phlebitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hepatobiliary disorders | ||||
Acute hepatic failure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Bile duct obstruction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bile duct stone | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Cardiac cirrhosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cholangitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cholangitis acute | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Cholecystitis | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Cholecystitis acute | 5/1863 (0.3%) | 2/1863 (0.1%) | ||
Cholecystitis chronic | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cholelithiasis | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Drug-induced liver injury | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Hepatic cirrhosis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Hepatic failure | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Hepatic function abnormal | 4/1863 (0.2%) | 1/1863 (0.1%) | ||
Hepatic steatosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hepatitis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Liver disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Liver injury | 5/1863 (0.3%) | 3/1863 (0.2%) | ||
Non-alcoholic steatohepatitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Immune system disorders | ||||
Heart transplant rejection | 1/1863 (0.1%) | 0/1863 (0%) | ||
Infections and infestations | ||||
Abdominal sepsis | 0/1863 (0%) | 2/1863 (0.1%) | ||
Appendicitis | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Appendicitis perforated | 0/1863 (0%) | 2/1863 (0.1%) | ||
Atypical pneumonia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bacteraemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Bacterial sepsis | 0/1863 (0%) | 2/1863 (0.1%) | ||
Bronchitis | 5/1863 (0.3%) | 5/1863 (0.3%) | ||
Bullous erysipelas | 1/1863 (0.1%) | 0/1863 (0%) | ||
COVID-19 | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
COVID-19 pneumonia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cellulitis | 3/1863 (0.2%) | 8/1863 (0.4%) | ||
Clostridium difficile infection | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cystitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Dengue fever | 1/1863 (0.1%) | 0/1863 (0%) | ||
Device related infection | 0/1863 (0%) | 2/1863 (0.1%) | ||
Diabetic foot infection | 0/1863 (0%) | 3/1863 (0.2%) | ||
Disseminated tuberculosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Diverticulitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Encephalitis viral | 1/1863 (0.1%) | 0/1863 (0%) | ||
Endocarditis | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Erysipelas | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
Escherichia bacteraemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Eye abscess | 1/1863 (0.1%) | 0/1863 (0%) | ||
Fournier's gangrene | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gangrene | 1/1863 (0.1%) | 4/1863 (0.2%) | ||
Gastritis viral | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gastroenteritis | 9/1863 (0.5%) | 4/1863 (0.2%) | ||
Gastrointestinal infection | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Haemorrhagic fever | 1/1863 (0.1%) | 0/1863 (0%) | ||
Herpes zoster | 2/1863 (0.1%) | 0/1863 (0%) | ||
Human anaplasmosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Implant site infection | 0/1863 (0%) | 1/1863 (0.1%) | ||
Infected skin ulcer | 0/1863 (0%) | 1/1863 (0.1%) | ||
Infection | 2/1863 (0.1%) | 0/1863 (0%) | ||
Infective spondylitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Influenza | 5/1863 (0.3%) | 4/1863 (0.2%) | ||
Intervertebral discitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Labyrinthitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Localised infection | 2/1863 (0.1%) | 0/1863 (0%) | ||
Lower respiratory tract infection | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Medical device site infection | 0/1863 (0%) | 1/1863 (0.1%) | ||
Nail infection | 1/1863 (0.1%) | 0/1863 (0%) | ||
Nocardiosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Osteomyelitis | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Osteomyelitis chronic | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pelvic abscess | 1/1863 (0.1%) | 0/1863 (0%) | ||
Perineal abscess | 1/1863 (0.1%) | 0/1863 (0%) | ||
Peritonitis | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Peritonitis bacterial | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pharyngitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pneumonia | 62/1863 (3.3%) | 53/1863 (2.8%) | ||
Pneumonia bacterial | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
Pneumonia chlamydial | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pneumonia influenzal | 0/1863 (0%) | 1/1863 (0.1%) | ||
Postoperative wound infection | 2/1863 (0.1%) | 0/1863 (0%) | ||
Pulmonary sepsis | 0/1863 (0%) | 2/1863 (0.1%) | ||
Pulmonary tuberculosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pyelitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pyelonephritis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pyelonephritis acute | 2/1863 (0.1%) | 0/1863 (0%) | ||
Respiratory syncytial virus bronchitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Respiratory tract infection | 0/1863 (0%) | 1/1863 (0.1%) | ||
Sepsis | 8/1863 (0.4%) | 8/1863 (0.4%) | ||
Septic encephalopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Septic shock | 5/1863 (0.3%) | 9/1863 (0.5%) | ||
Sinobronchitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Spinal cord abscess | 0/1863 (0%) | 2/1863 (0.1%) | ||
Staphylococcal bacteraemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Staphylococcal sepsis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Streptococcal sepsis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Upper respiratory tract infection | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Urinary tract infection | 10/1863 (0.5%) | 14/1863 (0.8%) | ||
Urosepsis | 0/1863 (0%) | 4/1863 (0.2%) | ||
Vessel puncture site cellulitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Viral diarrhoea | 1/1863 (0.1%) | 0/1863 (0%) | ||
Injury, poisoning and procedural complications | ||||
Ankle fracture | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Avulsion fracture | 0/1863 (0%) | 2/1863 (0.1%) | ||
Bladder injury | 0/1863 (0%) | 1/1863 (0.1%) | ||
Carbon monoxide poisoning | 1/1863 (0.1%) | 0/1863 (0%) | ||
Concussion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Contusion | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Coronary artery restenosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Costal cartilage fracture | 0/1863 (0%) | 1/1863 (0.1%) | ||
Craniocerebral injury | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Fall | 4/1863 (0.2%) | 15/1863 (0.8%) | ||
Femoral neck fracture | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Femur fracture | 3/1863 (0.2%) | 5/1863 (0.3%) | ||
Fibula fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Fracture | 0/1863 (0%) | 1/1863 (0.1%) | ||
Head injury | 0/1863 (0%) | 3/1863 (0.2%) | ||
Heat stroke | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hip fracture | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Humerus fracture | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Jaw fracture | 0/1863 (0%) | 1/1863 (0.1%) | ||
Joint dislocation | 1/1863 (0.1%) | 0/1863 (0%) | ||
Limb crushing injury | 0/1863 (0%) | 1/1863 (0.1%) | ||
Limb injury | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Lumbar vertebral fracture | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Multiple injuries | 2/1863 (0.1%) | 0/1863 (0%) | ||
Open globe injury | 1/1863 (0.1%) | 0/1863 (0%) | ||
Overdose | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pelvic fracture | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
Post procedural haemorrhage | 1/1863 (0.1%) | 0/1863 (0%) | ||
Post procedural swelling | 1/1863 (0.1%) | 0/1863 (0%) | ||
Post-traumatic pain | 1/1863 (0.1%) | 0/1863 (0%) | ||
Postoperative respiratory failure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Procedural shock | 0/1863 (0%) | 2/1863 (0.1%) | ||
Rib fracture | 2/1863 (0.1%) | 0/1863 (0%) | ||
Road traffic accident | 2/1863 (0.1%) | 4/1863 (0.2%) | ||
Skin laceration | 0/1863 (0%) | 2/1863 (0.1%) | ||
Spinal compression fracture | 0/1863 (0%) | 1/1863 (0.1%) | ||
Splenic rupture | 0/1863 (0%) | 1/1863 (0.1%) | ||
Subdural haematoma | 0/1863 (0%) | 2/1863 (0.1%) | ||
Subdural haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Thermal burn | 0/1863 (0%) | 1/1863 (0.1%) | ||
Tibia fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Tooth fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Toxicity to various agents | 1/1863 (0.1%) | 0/1863 (0%) | ||
Traumatic fracture | 0/1863 (0%) | 6/1863 (0.3%) | ||
Traumatic haematoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Traumatic intracranial haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Upper limb fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vascular pseudoaneurysm | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Wound dehiscence | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Wrist fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Investigations | ||||
Aspartate aminotransferase increased | 0/1863 (0%) | 1/1863 (0.1%) | ||
Blood creatinine increased | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cardiac electrophysiologic study | 1/1863 (0.1%) | 0/1863 (0%) | ||
Ejection fraction decreased | 1/1863 (0.1%) | 0/1863 (0%) | ||
Endoscopic retrograde cholangiopancreatography | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hepatic enzyme abnormal | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hepatic enzyme increased | 1/1863 (0.1%) | 0/1863 (0%) | ||
Weight increased | 1/1863 (0.1%) | 0/1863 (0%) | ||
Metabolism and nutrition disorders | ||||
Acidosis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Cachexia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Decreased appetite | 1/1863 (0.1%) | 0/1863 (0%) | ||
Dehydration | 4/1863 (0.2%) | 8/1863 (0.4%) | ||
Diabetes mellitus | 5/1863 (0.3%) | 4/1863 (0.2%) | ||
Diabetes mellitus inadequate control | 2/1863 (0.1%) | 0/1863 (0%) | ||
Diabetic complication | 1/1863 (0.1%) | 0/1863 (0%) | ||
Diabetic metabolic decompensation | 7/1863 (0.4%) | 2/1863 (0.1%) | ||
Gout | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
Hyperglycaemia | 2/1863 (0.1%) | 0/1863 (0%) | ||
Hyperglycaemic hyperosmolar nonketotic syndrome | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hyperkalaemia | 9/1863 (0.5%) | 2/1863 (0.1%) | ||
Hypernatraemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hypoglycaemia | 5/1863 (0.3%) | 6/1863 (0.3%) | ||
Hypokalaemia | 2/1863 (0.1%) | 3/1863 (0.2%) | ||
Hyponatraemia | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Hypophagia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hypovolaemia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Lactic acidosis | 0/1863 (0%) | 2/1863 (0.1%) | ||
Metabolic acidosis | 3/1863 (0.2%) | 4/1863 (0.2%) | ||
Type 2 diabetes mellitus | 0/1863 (0%) | 1/1863 (0.1%) | ||
Musculoskeletal and connective tissue disorders | ||||
Ankylosing spondylitis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Arthralgia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Arthropathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Back pain | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Cervical spinal stenosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Crystal arthropathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Gouty arthritis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Intervertebral disc disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Joint destruction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Lumbar spinal stenosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Muscular weakness | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Musculoskeletal chest pain | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Osteoarthritis | 7/1863 (0.4%) | 3/1863 (0.2%) | ||
Osteochondrosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pathological fracture | 1/1863 (0.1%) | 0/1863 (0%) | ||
Polymyalgia rheumatica | 1/1863 (0.1%) | 0/1863 (0%) | ||
Rhabdomyolysis | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Rotator cuff syndrome | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Spondylitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Systemic lupus erythematosus | 1/1863 (0.1%) | 0/1863 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Abdominal neoplasm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Adenocarcinoma gastric | 1/1863 (0.1%) | 0/1863 (0%) | ||
Adenocarcinoma of colon | 2/1863 (0.1%) | 2/1863 (0.1%) | ||
Adenocarcinoma of the cervix | 0/1863 (0%) | 1/1863 (0.1%) | ||
Adenocarcinoma pancreas | 2/1863 (0.1%) | 0/1863 (0%) | ||
Adrenal adenoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Basal cell carcinoma | 4/1863 (0.2%) | 4/1863 (0.2%) | ||
Bile duct adenocarcinoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bladder cancer | 3/1863 (0.2%) | 1/1863 (0.1%) | ||
Bladder cancer stage IV | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bladder neoplasm | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Bladder transitional cell carcinoma | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Bowen's disease | 1/1863 (0.1%) | 0/1863 (0%) | ||
Chronic lymphocytic leukaemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Chronic myelomonocytic leukaemia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Clear cell renal cell carcinoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Colon adenoma | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Colon cancer | 3/1863 (0.2%) | 0/1863 (0%) | ||
Cutaneous T-cell lymphoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Diffuse large B-cell lymphoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Diffuse large B-cell lymphoma recurrent | 0/1863 (0%) | 1/1863 (0.1%) | ||
Gastric cancer | 2/1863 (0.1%) | 0/1863 (0%) | ||
Gastrointestinal neoplasm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hepatic cancer | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hypergammaglobulinaemia benign monoclonal | 1/1863 (0.1%) | 0/1863 (0%) | ||
Invasive ductal breast carcinoma | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Lung neoplasm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Lung neoplasm malignant | 2/1863 (0.1%) | 0/1863 (0%) | ||
Malignant melanoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Metastases to spine | 0/1863 (0%) | 1/1863 (0.1%) | ||
Metastatic carcinoma of the bladder | 1/1863 (0.1%) | 0/1863 (0%) | ||
Metastatic neoplasm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Myelodysplastic syndrome | 2/1863 (0.1%) | 0/1863 (0%) | ||
Non-Hodgkin's lymphoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Oesophageal carcinoma | 2/1863 (0.1%) | 0/1863 (0%) | ||
Ovarian adenoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pancreatic carcinoma | 3/1863 (0.2%) | 0/1863 (0%) | ||
Pancreatic carcinoma metastatic | 0/1863 (0%) | 1/1863 (0.1%) | ||
Plasma cell myeloma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Prostate cancer | 7/1863 (0.4%) | 6/1863 (0.3%) | ||
Prostate cancer metastatic | 0/1863 (0%) | 1/1863 (0.1%) | ||
Rectal adenocarcinoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Renal cancer | 0/1863 (0%) | 1/1863 (0.1%) | ||
Renal cancer metastatic | 0/1863 (0%) | 1/1863 (0.1%) | ||
Renal neoplasm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Squamous cell carcinoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Squamous cell carcinoma of lung | 2/1863 (0.1%) | 0/1863 (0%) | ||
Squamous cell carcinoma of skin | 1/1863 (0.1%) | 6/1863 (0.3%) | ||
Transitional cell carcinoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Ureteric cancer | 0/1863 (0%) | 1/1863 (0.1%) | ||
Nervous system disorders | ||||
Brain injury | 0/1863 (0%) | 1/1863 (0.1%) | ||
Carotid arteriosclerosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Carotid artery occlusion | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Carotid artery stenosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cerebellar haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cerebellar infarction | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cerebellar stroke | 1/1863 (0.1%) | 0/1863 (0%) | ||
Cerebral haematoma | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cerebral haemorrhage | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Cerebral hypoperfusion | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cerebral infarction | 2/1863 (0.1%) | 4/1863 (0.2%) | ||
Cerebral ischaemia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cerebrovascular accident | 12/1863 (0.6%) | 17/1863 (0.9%) | ||
Cerebrovascular insufficiency | 0/1863 (0%) | 1/1863 (0.1%) | ||
Dementia | 3/1863 (0.2%) | 0/1863 (0%) | ||
Dizziness | 0/1863 (0%) | 1/1863 (0.1%) | ||
Dysarthria | 0/1863 (0%) | 1/1863 (0.1%) | ||
Embolic stroke | 0/1863 (0%) | 1/1863 (0.1%) | ||
Epilepsy | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Guillain-Barre syndrome | 1/1863 (0.1%) | 0/1863 (0%) | ||
Haemorrhagic stroke | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Headache | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hemiparesis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Hemiplegia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hepatic encephalopathy | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hyperglycaemic seizure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hypoxic-ischaemic encephalopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Intracranial aneurysm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Ischaemic stroke | 20/1863 (1.1%) | 19/1863 (1%) | ||
Lacunar infarction | 0/1863 (0%) | 1/1863 (0.1%) | ||
Loss of consciousness | 0/1863 (0%) | 2/1863 (0.1%) | ||
Lumbar radiculopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Lumbosacral radiculopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Migraine | 0/1863 (0%) | 1/1863 (0.1%) | ||
Myoclonus | 1/1863 (0.1%) | 0/1863 (0%) | ||
Paraplegia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Peroneal nerve palsy | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Postresuscitation encephalopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Presyncope | 0/1863 (0%) | 4/1863 (0.2%) | ||
Seizure | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Spinal cord compression | 0/1863 (0%) | 1/1863 (0.1%) | ||
Subarachnoid haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Syncope | 8/1863 (0.4%) | 17/1863 (0.9%) | ||
Transient ischaemic attack | 9/1863 (0.5%) | 5/1863 (0.3%) | ||
Uraemic encephalopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vascular dementia | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vascular encephalopathy | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vertebrobasilar insufficiency | 1/1863 (0.1%) | 0/1863 (0%) | ||
Product Issues | ||||
Device breakage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Device dislocation | 0/1863 (0%) | 1/1863 (0.1%) | ||
Device failure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Device inappropriate shock delivery | 0/1863 (0%) | 1/1863 (0.1%) | ||
Device lead damage | 1/1863 (0.1%) | 0/1863 (0%) | ||
Device lead issue | 0/1863 (0%) | 2/1863 (0.1%) | ||
Device malfunction | 4/1863 (0.2%) | 3/1863 (0.2%) | ||
Device physical property issue | 1/1863 (0.1%) | 0/1863 (0%) | ||
Psychiatric disorders | ||||
Anxiety | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bipolar disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Completed suicide | 0/1863 (0%) | 1/1863 (0.1%) | ||
Delirium | 4/1863 (0.2%) | 8/1863 (0.4%) | ||
Delirium tremens | 1/1863 (0.1%) | 0/1863 (0%) | ||
Depression | 1/1863 (0.1%) | 0/1863 (0%) | ||
Drug abuse | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hallucination | 0/1863 (0%) | 1/1863 (0.1%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 55/1863 (3%) | 35/1863 (1.9%) | ||
Azotaemia | 2/1863 (0.1%) | 0/1863 (0%) | ||
Chronic kidney disease | 6/1863 (0.3%) | 3/1863 (0.2%) | ||
Diabetic nephropathy | 0/1863 (0%) | 1/1863 (0.1%) | ||
Dysuria | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
End stage renal disease | 1/1863 (0.1%) | 0/1863 (0%) | ||
Haematuria | 2/1863 (0.1%) | 1/1863 (0.1%) | ||
Hydronephrosis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Nephrolithiasis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Nephropathy | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Nephropathy toxic | 1/1863 (0.1%) | 0/1863 (0%) | ||
Prerenal failure | 0/1863 (0%) | 1/1863 (0.1%) | ||
Renal failure | 14/1863 (0.8%) | 9/1863 (0.5%) | ||
Renal impairment | 27/1863 (1.4%) | 17/1863 (0.9%) | ||
Renal infarct | 1/1863 (0.1%) | 0/1863 (0%) | ||
Renal tubular necrosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Ureterolithiasis | 0/1863 (0%) | 3/1863 (0.2%) | ||
Urethral stenosis | 0/1863 (0%) | 2/1863 (0.1%) | ||
Urinary retention | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Reproductive system and breast disorders | ||||
Acquired hydrocele | 1/1863 (0.1%) | 0/1863 (0%) | ||
Balanoposthitis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Benign prostatic hyperplasia | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Fibrocystic breast disease | 0/1863 (0%) | 1/1863 (0.1%) | ||
Uterovaginal prolapse | 0/1863 (0%) | 1/1863 (0.1%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Acute pulmonary oedema | 2/1863 (0.1%) | 3/1863 (0.2%) | ||
Acute respiratory failure | 5/1863 (0.3%) | 3/1863 (0.2%) | ||
Aspiration | 1/1863 (0.1%) | 0/1863 (0%) | ||
Asthma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Asthmatic crisis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Bronchiectasis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Bronchitis chronic | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Chronic obstructive pulmonary disease | 13/1863 (0.7%) | 11/1863 (0.6%) | ||
Dyspnoea | 4/1863 (0.2%) | 7/1863 (0.4%) | ||
Dyspnoea exertional | 2/1863 (0.1%) | 0/1863 (0%) | ||
Epistaxis | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Haemoptysis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Haemothorax | 1/1863 (0.1%) | 0/1863 (0%) | ||
Idiopathic pulmonary fibrosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Lung disorder | 0/1863 (0%) | 2/1863 (0.1%) | ||
Organising pneumonia | 0/1863 (0%) | 1/1863 (0.1%) | ||
Paranasal cyst | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pleural effusion | 5/1863 (0.3%) | 2/1863 (0.1%) | ||
Pleuritic pain | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pneumonia aspiration | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Pneumonitis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pneumothorax | 3/1863 (0.2%) | 3/1863 (0.2%) | ||
Pulmonary arterial hypertension | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pulmonary congestion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pulmonary embolism | 4/1863 (0.2%) | 5/1863 (0.3%) | ||
Pulmonary fibrosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Pulmonary hypertension | 3/1863 (0.2%) | 2/1863 (0.1%) | ||
Pulmonary oedema | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Respiratory acidosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Respiratory failure | 5/1863 (0.3%) | 2/1863 (0.1%) | ||
Sleep apnoea syndrome | 2/1863 (0.1%) | 0/1863 (0%) | ||
Vocal cord thickening | 1/1863 (0.1%) | 0/1863 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Actinic keratosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Angioedema | 3/1863 (0.2%) | 0/1863 (0%) | ||
Dermatitis bullous | 0/1863 (0%) | 1/1863 (0.1%) | ||
Diabetic foot | 2/1863 (0.1%) | 6/1863 (0.3%) | ||
Eczema | 0/1863 (0%) | 1/1863 (0.1%) | ||
Pemphigoid | 0/1863 (0%) | 1/1863 (0.1%) | ||
Skin ulcer | 3/1863 (0.2%) | 4/1863 (0.2%) | ||
Stasis dermatitis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Surgical and medical procedures | ||||
Cardiac resynchronisation therapy | 0/1863 (0%) | 1/1863 (0.1%) | ||
Cardioversion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Coronary arterial stent insertion | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hip arthroplasty | 2/1863 (0.1%) | 0/1863 (0%) | ||
Implantable defibrillator insertion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Percutaneous coronary intervention | 0/1863 (0%) | 1/1863 (0.1%) | ||
Vascular disorders | ||||
Aortic aneurysm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Aortic dissection | 1/1863 (0.1%) | 0/1863 (0%) | ||
Aortic intramural haematoma | 1/1863 (0.1%) | 0/1863 (0%) | ||
Aortic stenosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Arterial thrombosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Arteriosclerosis | 2/1863 (0.1%) | 0/1863 (0%) | ||
Bleeding varicose vein | 1/1863 (0.1%) | 0/1863 (0%) | ||
Circulatory collapse | 5/1863 (0.3%) | 0/1863 (0%) | ||
Deep vein thrombosis | 5/1863 (0.3%) | 4/1863 (0.2%) | ||
Diabetic vascular disorder | 1/1863 (0.1%) | 0/1863 (0%) | ||
Dry gangrene | 0/1863 (0%) | 1/1863 (0.1%) | ||
Embolism | 0/1863 (0%) | 1/1863 (0.1%) | ||
Extremity necrosis | 1/1863 (0.1%) | 2/1863 (0.1%) | ||
Femoral artery embolism | 0/1863 (0%) | 1/1863 (0.1%) | ||
Hypertension | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hypertensive crisis | 4/1863 (0.2%) | 6/1863 (0.3%) | ||
Hypertensive emergency | 1/1863 (0.1%) | 0/1863 (0%) | ||
Hypertensive urgency | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Hypotension | 13/1863 (0.7%) | 14/1863 (0.8%) | ||
Hypovolaemic shock | 1/1863 (0.1%) | 0/1863 (0%) | ||
Intermittent claudication | 0/1863 (0%) | 1/1863 (0.1%) | ||
Leriche syndrome | 0/1863 (0%) | 2/1863 (0.1%) | ||
Lymphocele | 1/1863 (0.1%) | 0/1863 (0%) | ||
Orthostatic hypotension | 1/1863 (0.1%) | 4/1863 (0.2%) | ||
Peripheral arterial occlusive disease | 4/1863 (0.2%) | 7/1863 (0.4%) | ||
Peripheral artery aneurysm | 0/1863 (0%) | 1/1863 (0.1%) | ||
Peripheral artery stenosis | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Peripheral artery thrombosis | 0/1863 (0%) | 1/1863 (0.1%) | ||
Peripheral embolism | 2/1863 (0.1%) | 0/1863 (0%) | ||
Peripheral ischaemia | 4/1863 (0.2%) | 5/1863 (0.3%) | ||
Peripheral vascular disorder | 0/1863 (0%) | 1/1863 (0.1%) | ||
Shock haemorrhagic | 0/1863 (0%) | 1/1863 (0.1%) | ||
Subclavian artery occlusion | 1/1863 (0.1%) | 1/1863 (0.1%) | ||
Subclavian vein occlusion | 1/1863 (0.1%) | 0/1863 (0%) | ||
Subgaleal haemorrhage | 0/1863 (0%) | 1/1863 (0.1%) | ||
Thrombosis | 1/1863 (0.1%) | 0/1863 (0%) | ||
Vascular insufficiency | 0/1863 (0%) | 1/1863 (0.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
Placebo | 10 mg Empagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 369/1863 (19.8%) | 328/1863 (17.6%) | ||
Infections and infestations | ||||
Nasopharyngitis | 94/1863 (5%) | 89/1863 (4.8%) | ||
Metabolism and nutrition disorders | ||||
Hyperkalaemia | 109/1863 (5.9%) | 99/1863 (5.3%) | ||
Hyperuricaemia | 115/1863 (6.2%) | 63/1863 (3.4%) | ||
Vascular disorders | ||||
Hypotension | 109/1863 (5.9%) | 120/1863 (6.4%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Name/Title | Boehringer Ingelheim, Call Centre |
---|---|
Organization | Boehringer Ingelheim |
Phone | 1-800-243-0127 |
clintriage.rdg@boehringer-ingelheim.com |
- 1245.121
- 2016-002280-34