VA NEPHRON-D: Diabetes iN Nephropathy Study
Sponsor
US Department of Veterans Affairs (U.S. Fed)
Overall Status
Terminated
CT.gov ID
NCT00555217
Collaborator
(none)
1,448
31
2
75
46.7
0.6
Study Details
Study Description
Brief Summary
Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. The overall rate of ESRD secondary to diabetes has risen 68% since 1992. Medications that block the renin angiotensin system have been shown to decrease the progression of diabetic nephropathy. The use of an angiotensin receptor blocker (ARB) has been shown to decrease the risk of progression of kidney disease in two studies of individuals with Type 2 diabetes and proteinuria. Despite the use of an ARB, the incidence of renal failure remained high in the treated group in both studies. The combination of an angiotensin converting enzyme inhibitor (ACEI) and ARB can lead to more complete blockade of the renin angiotensin system. In diabetic kidney disease, combination therapy has been shown to decrease proteinuria in short-term studies. Although there are encouraging results for improvement in proteinuria there are no data on progression of kidney disease for the use of combination of ACEI and ARB therapy in patients with diabetes. In addition, there could be an increased risk of serious hyperkalemia in individuals with diabetes who receive combination ACEI and ARB. The investigators therefore propose a randomized double blind multi-center clinical trial to assess the effect of combination of ACEI and ARB in patients with diabetes and proteinuria on progression of kidney disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
Primary Hypothesis:
To evaluate the combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) vs. standard treatment with angiotensin receptor blocker on the progression of kidney disease in individuals with Type 2 diabetes and overt nephropathy.
The primary outcome is a composite endpoint of reduction in estimated GFR of 30 ml/min/1.73mm in individuals with an estimated baseline GFR greater than or equal to 60 ml/min/1.73mm; reduction in estimated GFR of greater than 50% in individuals with an estimated baseline GFR less than 60 mL/min/1.73mm; progression to end-stage renal disease (defined as need for dialysis, renal transplant or an eGFR less than 15 ml/min/1.73mm) or death.
Secondary outcome: a renal composite endpoint, defined as; reduction in estimated GFR of more than 50% (for individuals with a baseline estimated GFR less than 60 ml/min/1.73mm); reduction in estimated GFR of more than 30 ml/min/1.73mm (for individuals with a baseline estimated GFR greater than or equal to 60 ml/min/1.73mm) or progression to end-stage renal disease (defined as need for dialysis, renal transplant or an eGFR of less than 15 ml/min/1.73mm).
Tertiary outcomes are cardiovascular events (cardiovascular mortality, myocardial infarction, cerebrovascular accident, admission for heart failure), change in albuminuria at 12 months and decline in slope of kidney function.
Study Abstract:
The study is a multi-center, prospective, randomized, parallel group trial to test the efficacy of the combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotension receptor blocker (ARB) vs. standard treatment with angiotension receptor blocker on the combined end-point. The primary outcome is a composite endpoint of reduction in estimated GFR of 30 ml/min/1.73mm in individuals with an estimated GFR greater than or equal to 60 ml/min/1.73mm; reduction in estimated GFR of greater than 50% in individuals with an estimated GFR less than 60 ml/min/1.73mm; progression to end-stage renal disease (defined as need for dialysis, renal transplant or en eGFR less than 15 ml/min/1.73mm)or death. The study population is individuals with type 2 diabetes and overt nephropathy.
Eligible subjects who consent to participate will be randomized into either the combination therapy arm or the mono therapy arm. The randomization will be stratified by site and within sites by baseline albuminuria (< 1 vs. greater than or equal to 1 gram/gram creatinine) and eGFR (< 60 vs. greater than or equal to 60 ml/min/1.73m*m). All participants will receive open label therapy with losartan, an ARB, as standard of care. Patients not treated with an ACEI or ARB will be initiated on losartan; patients treated with an ACEI or ARB other than losartan (the study ARB) will be converted to losartan (the study ARB) and the dose titrated to 100 mg/day. Individuals who tolerate ARB 100mg/day criteria will be randomized in a 1:1 ratio to the addition of blinded lisinopril (the study ACEI) or placebo. The medication (lisinopril or placebo) will be titrated from an initial dose of 10 mg/day to a target dose of 40 mg/day. After each adjustment in dose, serum chemistries will be evaluated for kidney function and potassium levels. Subjects will be enrolled over a period of 4.25 years and the maximum length of follow-up is 6.25 years. The planned study duration is 6.25 years with 4.25 years of accrual and 6.25 years of follow-up for all enrolled patients. The intervention was stopped on November 7, 2012 for safety concerns after an interim analysis. Patients are still under passively follow-up without intervention.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1448 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
CSP #565 - Combination Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D Study)
Study Start Date
:
Jul 1, 2008
Actual Primary Completion Date
:
Sep 1, 2014
Actual Study Completion Date
:
Oct 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Combination of ARB and ACEI Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) |
Drug: losartan
50 or 100mg/day
Drug: lisinopril
10, 20 or 40 mg/day
|
| Active Comparator: Monotherapy ARB Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) |
Drug: losartan
50 or 100mg/day
|
Outcome Measures
Primary Outcome Measures
- A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death [From enrollemnt to time of first primary event, up to 4.5 years]
Time to the first event of reduction in estimated GFR of 30ml/min/1.73m*m in individuals w/a baseline estimated GFR >= 60 ml/min/1.73m*m, reduction in estimated GFR >50% in individuals w/ baseline estimated GFR <60ml/min/1.73m*m; ESRD or death.
Secondary Outcome Measures
- A Renal Composite Endpoint, Defined as; Reduction in Estimated GFR of >50% (for Individuals With Baseline GFR <60) or Reduction in GFR of >30 (for Individuals With Baseline GFR >= GFR 60) or ESRD. [From enrollment to time of first event, up to 4.5 years]
Time to the first event of reduction in estimated GFR of >50% (for individuals with baseline GFR <60) or reduction in GFR of >30 (for individuals with baseline GFR >= GFR 60) or ESRD.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Type 2 diabetes
-
Albuminuria >300mg/gram creatinine
-
Stage 2 or 3 CKD (eGFR 30 to <90 mg/min/1.73m*2 )
-
Able to give informed consent
-
Telephone contact available
Exclusion Criteria:
-
History of intolerance to ACEI or ARB
-
Serum potassium level >5.5 meq/L
-
Receiving sodium polystyrene sulfonate (Kayexalate)
-
Pregnancy, breast feeding, planning to become pregnant or sexually active and not using birth control
-
Renal transplant recipient
-
Suspected non-diabetic kidney disease
-
Inability to discontinue current use of ACEI/ARB combination
-
Current use of Lithium
-
Severe (end-stage) comorbid disease
-
Prisoner
-
Age <18
-
Estimated glomerular filtration rate (GFR) <30 or >=90 ml/min/1.73m*m
-
HbA1c >10.5%
-
Patient refusal
-
Participation in a concurrent interventional study
-
Blood pressure >180/95
-
Unwilling to stop any proscribed medications after enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Carl T. Hayden VA Medical Center | Phoenix | Arizona | United States | 85012 |
| 2 | Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock | Little Rock | Arkansas | United States | 72205-5484 |
| 3 | VA Medical Center, Loma Linda | Loma Linda | California | United States | 92357 |
| 4 | VA Palo Alto Health Care System | Palo Alto | California | United States | 94304-1290 |
| 5 | VA Connecticut Health Care System (West Haven) | West Haven | Connecticut | United States | 06516 |
| 6 | North Florida/South Georgia Veterans Health System | Gainesville | Florida | United States | 32608 |
| 7 | VA Medical Center, Miami | Miami | Florida | United States | 33125 |
| 8 | James A. Haley Veterans Hospital, Tampa | Tampa | Florida | United States | 33612 |
| 9 | Edward Hines, Jr. VA Hospital | Hines | Illinois | United States | 60141-5000 |
| 10 | Richard Roudebush VA Medical Center, Indianapolis | Indianapolis | Indiana | United States | 46202-2884 |
| 11 | VA Medical Center, Iowa City | Iowa City | Iowa | United States | 52246-2208 |
| 12 | VA Maryland Health Care System, Baltimore | Baltimore | Maryland | United States | 21201 |
| 13 | VA Medical Center, Minneapolis | Minneapolis | Minnesota | United States | 55417 |
| 14 | VA Medical Center, Kansas City MO | Kansas City | Missouri | United States | 64128 |
| 15 | VA Medical Center, St Louis | St Louis | Missouri | United States | 63106 |
| 16 | VA Medical Center, Omaha | Omaha | Nebraska | United States | 68105-1873 |
| 17 | VA New Jersey Health Care System, East Orange | East Orange | New Jersey | United States | 07018 |
| 18 | New Mexico VA Health Care System, Albuquerque | Albuquerque | New Mexico | United States | 87108-5153 |
| 19 | VA Western New York Healthcare System at Buffalo | Buffalo | New York | United States | 14215 |
| 20 | VA Medical Center, Durham | Durham | North Carolina | United States | 27705 |
| 21 | VA Medical Center, Cleveland | Cleveland | Ohio | United States | 44106 |
| 22 | VA Medical Center, Portland | Portland | Oregon | United States | 97201 |
| 23 | VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA | Pittsburgh | Pennsylvania | United States | 15240 |
| 24 | Ralph H Johnson VA Medical Center, Charleston | Charleston | South Carolina | United States | 29401-5799 |
| 25 | WJB Dorn Veterans Hospital, Columbia | Columbia | South Carolina | United States | 29209 |
| 26 | VA Medical Center, Memphis | Memphis | Tennessee | United States | 38104 |
| 27 | VA Medical Center | Nashville | Tennessee | United States | 37212-2637 |
| 28 | VA North Texas Health Care System, Dallas | Dallas | Texas | United States | 75216 |
| 29 | Hunter Holmes McGuire VA Medical Center | Richmond | Virginia | United States | 23249 |
| 30 | Zablocki VA Medical Center, Milwaukee | Milwaukee | Wisconsin | United States | 53295-1000 |
| 31 | VA Medical Center, San Juan | San Juan | Puerto Rico | 00921 |
Sponsors and Collaborators
- US Department of Veterans Affairs
Investigators
- Study Chair: Linda Fried, MD MPH, VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Study Documents (Full-Text)
None provided.More Information
Publications
Responsible Party:
US Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00555217
Other Study ID Numbers:
- 565
First Posted:
Nov 8, 2007
Last Update Posted:
May 29, 2015
Last Verified:
May 1, 2015
Keywords provided by US Department of Veterans Affairs
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Combination of ARB and ACEI | Monotherapy ARB |
|---|---|---|
| Arm/Group Description | Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) losartan: 50 or 100mg/day lisinopril: 10, 20 or 40 mg/day | Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) losartan: 50 or 100mg/day |
| Period Title: Overall Study | ||
| STARTED | 724 | 724 |
| COMPLETED | 649 | 656 |
| NOT COMPLETED | 75 | 68 |
Baseline Characteristics
| Arm/Group Title | Combination of ARB and ACEI | Monotherapy ARB | Total |
|---|---|---|---|
| Arm/Group Description | Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) losartan: 50 or 100mg/day lisinopril: 10, 20 or 40 mg/day | Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) losartan: 50 or 100mg/day | Total of all reporting groups |
| Overall Participants | 724 | 724 | 1448 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.5
(7.9)
|
64.7
(7.7)
|
64.6
(7.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
1.2%
|
3
0.4%
|
12
0.8%
|
| Male |
715
98.8%
|
721
99.6%
|
1436
99.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
71
9.8%
|
75
10.4%
|
146
10.1%
|
| Not Hispanic or Latino |
653
90.2%
|
649
89.6%
|
1302
89.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
16
2.2%
|
25
3.5%
|
41
2.8%
|
| Asian |
4
0.6%
|
6
0.8%
|
10
0.7%
|
| Native Hawaiian or Other Pacific Islander |
8
1.1%
|
5
0.7%
|
13
0.9%
|
| Black or African American |
172
23.8%
|
160
22.1%
|
332
22.9%
|
| White |
523
72.2%
|
514
71%
|
1037
71.6%
|
| More than one race |
0
0%
|
14
1.9%
|
14
1%
|
| Unknown or Not Reported |
1
0.1%
|
0
0%
|
1
0.1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
724
100%
|
724
100%
|
1448
100%
|
| Body Mass Index (kg/m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m^2] |
34.9
(6.7)
|
34.3
(6.9)
|
34.6
(6.8)
|
| Coronary Artery Disease (participants) [Number] | |||
| Yes |
159
22%
|
167
23.1%
|
326
22.5%
|
| No |
565
78%
|
557
76.9%
|
1122
77.5%
|
| Congestive Heart Failure (participants) [Number] | |||
| Yes |
116
16%
|
110
15.2%
|
226
15.6%
|
| No |
608
84%
|
614
84.8%
|
1222
84.4%
|
| Retinopathy (participants) [Number] | |||
| Yes |
309
42.7%
|
310
42.8%
|
619
42.7%
|
| No |
415
57.3%
|
414
57.2%
|
829
57.3%
|
| SBP (mmHg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mmHg] |
136.9
(16.5)
|
137.0
(16.0)
|
136.9
(16.3)
|
| DBP (mmHg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mmHg] |
72.5
(10.6)
|
72.8
(9.9)
|
72.7
(10.2)
|
| Total Cholesterol (mg/dl) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dl] |
157.9
(43.6)
|
159.0
(40.5)
|
158.4
(42.1)
|
| LDL cholesterol (mg/dl) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dl] |
81.6
(32.4)
|
84.3
(35.0)
|
82.9
(33.7)
|
| HDL cholesterol (mg/dl) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dl] |
37.7
(11.0)
|
38.7
(11.3)
|
38.2
(11.2)
|
| Triglycerides (mg/dl) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mg/dl] |
165
|
162
|
163
|
| HbA1c (%) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [%] |
7.8
(1.2)
|
7.8
(1.3)
|
7.8
(1.3)
|
| serum Creatinine at enrollment (mg/dl) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dl] |
1.5
(0.4)
|
1.5
(0.4)
|
1.5
(0.4)
|
| Potassium (meq/L) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [meq/L] |
4.3
(0.5)
|
4.3
(0.5)
|
4.3
(0.5)
|
| eGFR at enrollment (ml/min/1.73m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [ml/min/1.73m^2] |
53.6
(15.5)
|
53.7
(16.2)
|
53.7
(15.9)
|
| urine albumin/creatinine at enrollment (mg/g) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mg/g] |
841.5
|
861.5
|
851.0
|
Outcome Measures
| Title | A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death |
|---|---|
| Description | Time to the first event of reduction in estimated GFR of 30ml/min/1.73m*m in individuals w/a baseline estimated GFR >= 60 ml/min/1.73m*m, reduction in estimated GFR >50% in individuals w/ baseline estimated GFR <60ml/min/1.73m*m; ESRD or death. |
| Time Frame | From enrollemnt to time of first primary event, up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Combination of ARB and ACEI | Monotherapy ARB |
|---|---|---|
| Arm/Group Description | Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) | Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) |
| Measure Participants | 724 | 724 |
| Number [participants] |
132
18.2%
|
152
21%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination of ARB and ACEI, Monotherapy ARB |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.30 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Combination ARB and ACEI vs. mono therapy ARB | |
| Title | A Renal Composite Endpoint, Defined as; Reduction in Estimated GFR of >50% (for Individuals With Baseline GFR <60) or Reduction in GFR of >30 (for Individuals With Baseline GFR >= GFR 60) or ESRD. |
|---|---|
| Description | Time to the first event of reduction in estimated GFR of >50% (for individuals with baseline GFR <60) or reduction in GFR of >30 (for individuals with baseline GFR >= GFR 60) or ESRD. |
| Time Frame | From enrollment to time of first event, up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Combination of ARB and ACEI | Monotherapy ARB |
|---|---|---|
| Arm/Group Description | Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) | Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) |
| Measure Participants | 724 | 724 |
| Number [participants] |
77
10.6%
|
101
14%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Combination of ARB and ACEI, Monotherapy ARB |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.10 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Combination ARB and ACEI vs. mono therapy ARB | |
Adverse Events
| Time Frame | July 2008 - January 2013 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Combination of ARB and ACEI | Monotherapy ARB | ||
| Arm/Group Description | Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) | Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB) | ||
All Cause Mortality |
||||
| Combination of ARB and ACEI | Monotherapy ARB | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Combination of ARB and ACEI | Monotherapy ARB | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 416/724 (57.5%) | 380/724 (52.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia of chronic disease | 0/724 (0%) | 0 | 1/724 (0.1%) | 2 |
| Anaemia of malignant disease | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Anemia | 15/724 (2.1%) | 23 | 12/724 (1.7%) | 13 |
| Coagulopathy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Idiopathic thrombocytopenic pu | 0/724 (0%) | 0 | 1/724 (0.1%) | 3 |
| Iron deficiency anaemia | 2/724 (0.3%) | 3 | 3/724 (0.4%) | 3 |
| Leukocytosis | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Normochromic normocytic anaemi | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Pancytopenia | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Thrombocytopenia | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 3/724 (0.4%) | 3 | 7/724 (1%) | 8 |
| Acute myocardial infarction | 27/724 (3.7%) | 31 | 24/724 (3.3%) | 25 |
| Angina pectoris | 7/724 (1%) | 8 | 9/724 (1.2%) | 11 |
| Angina unstable | 4/724 (0.6%) | 4 | 2/724 (0.3%) | 2 |
| Arrhythmia | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Atrial fibrillation | 13/724 (1.8%) | 18 | 14/724 (1.9%) | 19 |
| Atrial flutter | 5/724 (0.7%) | 5 | 3/724 (0.4%) | 3 |
| Atrioventricular block | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Atrioventricular block complet | 3/724 (0.4%) | 3 | 4/724 (0.6%) | 4 |
| Atrioventricular block first d | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Atrioventricular block second | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Bradycardia | 8/724 (1.1%) | 8 | 6/724 (0.8%) | 6 |
| Bundle branch block right | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cardiac arrest | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Cardiac failure | 7/724 (1%) | 8 | 6/724 (0.8%) | 6 |
| Cardiac failure acute | 2/724 (0.3%) | 2 | 3/724 (0.4%) | 4 |
| Cardiac failure chronic | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Cardiac failure congestive | 80/724 (11%) | 143 | 95/724 (13.1%) | 155 |
| Cardiac tamponade | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cardio-respiratory arrest | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Cardiogenic shock | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cardiomyopathy | 2/724 (0.3%) | 3 | 2/724 (0.3%) | 2 |
| Cardiorenal syndrome | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Cardiovascular disorder | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Coronary artery disease | 32/724 (4.4%) | 35 | 23/724 (3.2%) | 26 |
| Coronary artery occlusion | 6/724 (0.8%) | 7 | 4/724 (0.6%) | 4 |
| Coronary artery stenosis | 7/724 (1%) | 7 | 7/724 (1%) | 7 |
| Coronary artery thrombosis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Diastolic dysfunction | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypertensive heart disease | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intracardiac thrombus | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ischaemic cardiomyopathy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Mitral valve incompetence | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Myocardial infarction | 18/724 (2.5%) | 18 | 15/724 (2.1%) | 17 |
| Myocardial ischaemia | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Nodal arrhythmia | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Nodal rhythm | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Pericardial effusion | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pericarditis | 0/724 (0%) | 0 | 2/724 (0.3%) | 3 |
| Rhythm idioventricular | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Right ventricular failure | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Sick sinus syndrome | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Sinus bradycardia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Supraventricular tachycardia | 3/724 (0.4%) | 3 | 1/724 (0.1%) | 1 |
| Tachycardia | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Trifascicular block | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Ventricular tachycardia | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Haemorrhagic arteriovenous mal | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Cerumen impaction | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Meniere's disease | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Vertigo | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Vertigo positional | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Endocrine disorders | ||||
| Adrenal mass | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Goitre | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hyperparathyroidism | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Eye disorders | ||||
| Amaurosis fugax | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cataract | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Conjunctivitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Diplopia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Glaucoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Iridocyclitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Retinal detachment | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Visual acuity reduced | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 4/724 (0.6%) | 4 | 2/724 (0.3%) | 2 |
| Abdominal pain upper | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Abdominal wall haematoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Abdominal wall haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ascites | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Colitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Colonic polyp | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Colonic pseudo-obstruction | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Constipation | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Diarrhoea | 10/724 (1.4%) | 11 | 4/724 (0.6%) | 4 |
| Diverticulum intestinal | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Diverticulum intestinal haemor | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Duodenal ulcer | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Dyspepsia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Enterocolitis haemorrhagic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Flatulence | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Gastric ulcer | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Gastric varices haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastritis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastritis haemorrhagic | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Gastrointestinal haemorrhage | 14/724 (1.9%) | 17 | 5/724 (0.7%) | 5 |
| Gastrointestinal oedema | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Gastrointestinal ulcer haemorr | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastrooesophageal reflux disea | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Haemorrhoids | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ileus | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Impaired gastric emptying | 2/724 (0.3%) | 5 | 0/724 (0%) | 0 |
| Intestinal mass | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intestinal obstruction | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Intestinal perforation | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intestinal polyp haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Large intestinal ulcer | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Lower gastrointestinal haemorr | 2/724 (0.3%) | 2 | 2/724 (0.3%) | 2 |
| Oesophageal spasm | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Oesophagitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pancreatitis | 4/724 (0.6%) | 4 | 2/724 (0.3%) | 4 |
| Pancreatitis acute | 1/724 (0.1%) | 2 | 2/724 (0.3%) | 2 |
| Pancreatitis chronic | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Peritoneal perforation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pneumatosis intestinalis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Rectal haemorrhage | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Retroperitoneal haematoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Retroperitoneal haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Small intestinal obstruction | 7/724 (1%) | 7 | 2/724 (0.3%) | 4 |
| Small intestinal perforation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Swollen tongue | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Umbilical hernia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Upper gastrointestinal haemorr | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Vomiting | 4/724 (0.6%) | 4 | 3/724 (0.4%) | 3 |
| General disorders | ||||
| Adverse drug reaction | 4/724 (0.6%) | 5 | 2/724 (0.3%) | 2 |
| Asthenia | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Chest discomfort | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Chest pain | 24/724 (3.3%) | 27 | 21/724 (2.9%) | 26 |
| Death | 25/724 (3.5%) | 25 | 13/724 (1.8%) | 13 |
| Device malfunction | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Disease progression | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hernia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hernia obstructive | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Hypothermia | 0/724 (0%) | 0 | 1/724 (0.1%) | 2 |
| Impaired healing | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Medical device complication | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Non-cardiac chest pain | 7/724 (1%) | 7 | 6/724 (0.8%) | 6 |
| Oedema | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Oedema peripheral | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Pain | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Pyrexia | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Sudden cardiac death | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Swelling | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Systemic inflammatory response | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Cholecystitis | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Cholecystitis acute | 4/724 (0.6%) | 4 | 1/724 (0.1%) | 1 |
| Cholelithiasis | 4/724 (0.6%) | 4 | 4/724 (0.6%) | 4 |
| Gallbladder disorder | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hepatic congestion | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Portal vein thrombosis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Immune system disorders | ||||
| Amyloidosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 2 |
| Drug hypersensitivity | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Infections and infestations | ||||
| Abscess limb | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Appendicitis | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Appendicitis perforated | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Arthritis bacterial | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Bacteraemia | 4/724 (0.6%) | 4 | 0/724 (0%) | 0 |
| Bacterial infection | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Bacterial pyelonephritis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Bronchitis | 3/724 (0.4%) | 3 | 4/724 (0.6%) | 4 |
| Bronchitis bacterial | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Candidiasis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cellulitis | 33/724 (4.6%) | 46 | 31/724 (4.3%) | 39 |
| Cellulitis staphylococcal | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Clostridial infection | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Clostridium difficile colitis | 6/724 (0.8%) | 6 | 2/724 (0.3%) | 2 |
| Device related infection | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Diverticulitis | 2/724 (0.3%) | 2 | 2/724 (0.3%) | 2 |
| Ear infection | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Emphysematous pyelonephritis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Enterobacter bacteraemia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Epiglottitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Escherichia bacteraemia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Escherichia infection | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| External ear cellulitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gangrene | 6/724 (0.8%) | 7 | 4/724 (0.6%) | 5 |
| Gastroenteritis | 9/724 (1.2%) | 10 | 4/724 (0.6%) | 4 |
| Gastroenteritis clostridial | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastroenteritis viral | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Graft infection | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Groin abscess | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Haemophilus infection | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Herpes zoster | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Infected bites | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Infected skin ulcer | 3/724 (0.4%) | 4 | 1/724 (0.1%) | 1 |
| Infection | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Influenza | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Intervertebral discitis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Labyrinthitis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Lobar pneumonia | 6/724 (0.8%) | 6 | 5/724 (0.7%) | 5 |
| Localised infection | 2/724 (0.3%) | 3 | 1/724 (0.1%) | 1 |
| Lymphangitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Nosocomial infection | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Oesophageal candidiasis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Orchitis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Osteomyelitis | 13/724 (1.8%) | 17 | 13/724 (1.8%) | 15 |
| Osteomyelitis acute | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Osteomyelitis chronic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Otitis media | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Peptostreptococcus infection | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Perirectal abscess | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pertussis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pneumonia | 43/724 (5.9%) | 50 | 41/724 (5.7%) | 43 |
| Pneumonia bacterial | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pneumonia influenzal | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pneumonia klebsiella | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Pneumonia legionella | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pneumonia staphylococcal | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pneumonia streptococcal | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Post procedural infection | 3/724 (0.4%) | 3 | 1/724 (0.1%) | 1 |
| Postoperative wound infection | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Pseudomonas infection | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pyelonephritis | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Respiratory tract infection | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Scrotal abscess | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Sepsis | 5/724 (0.7%) | 5 | 3/724 (0.4%) | 3 |
| Sepsis syndrome | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Septic shock | 1/724 (0.1%) | 2 | 2/724 (0.3%) | 2 |
| Staphylococcal infection | 6/724 (0.8%) | 6 | 4/724 (0.6%) | 4 |
| Staphylococcal sepsis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Streptococcal bacteraemia | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Subcutaneous abscess | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Subdural empyema | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Tinea pedis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Upper respiratory tract infect | 2/724 (0.3%) | 2 | 2/724 (0.3%) | 2 |
| Urinary tract infection | 14/724 (1.9%) | 16 | 9/724 (1.2%) | 10 |
| Urosepsis | 3/724 (0.4%) | 3 | 2/724 (0.3%) | 2 |
| Viral cardiomyopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| West Nile viral infection | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Wound infection | 4/724 (0.6%) | 5 | 1/724 (0.1%) | 1 |
| Wound infection staphylococcal | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Accident at home | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Accident at work | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Accidental overdose | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Animal bite | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Ankle fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Arteriovenous fistula site com | 3/724 (0.4%) | 3 | 1/724 (0.1%) | 1 |
| Arteriovenous fistula thrombos | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Arthropod bite | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Cardiac procedure complication | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Contrast media reaction | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Coronary artery restenosis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Fall | 17/724 (2.3%) | 18 | 20/724 (2.8%) | 22 |
| Femur fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Foreign body | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Gastroenteritis radiation | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Head injury | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Heat stroke | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hip fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| In-stent coronary artery reste | 4/724 (0.6%) | 4 | 1/724 (0.1%) | 1 |
| Incorrect dose administered | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Injury | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Limb injury | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Lower limb fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Medication error | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Overdose | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Patella fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Post procedural complication | 6/724 (0.8%) | 6 | 5/724 (0.7%) | 5 |
| Post procedural haematoma | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Post procedural haemorrhage | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Postoperative fever | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Postoperative wound complicati | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Procedural complication | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Procedural hypertension | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Procedural vomiting | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Radiation dysphagia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Radiation pneumonitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Road traffic accident | 2/724 (0.3%) | 2 | 9/724 (1.2%) | 11 |
| Spinal compression fracture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Subdural haematoma | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Subdural haemorrhage | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Toxicity to various agents | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Vascular graft complication | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Vascular graft occlusion | 1/724 (0.1%) | 2 | 1/724 (0.1%) | 1 |
| Vascular pseudoaneurysm | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Wound dehiscence | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Investigations | ||||
| Antibiotic resistant Staphyloc | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Anticoagulation drug level abo | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Anticoagulation drug level bel | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Biopsy kidney | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Biopsy lung | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Blood bicarbonate decreased | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Blood creatine phosphokinase i | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Blood creatinine increased | 2/724 (0.3%) | 2 | 3/724 (0.4%) | 3 |
| Blood glucose decreased | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Blood glucose increased | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Blood potassium increased | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Electrocardiogram change | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Fistulogram | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Heart rate irregular | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| International normalised ratio | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 7/724 (1%) | 7 | 3/724 (0.4%) | 3 |
| Diabetes mellitus inadequate c | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Diabetic ketoacidosis | 3/724 (0.4%) | 3 | 1/724 (0.1%) | 3 |
| Fluid overload | 7/724 (1%) | 12 | 6/724 (0.8%) | 6 |
| Gout | 5/724 (0.7%) | 6 | 6/724 (0.8%) | 7 |
| Hypercalcaemia | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Hyperglycaemia | 7/724 (1%) | 10 | 16/724 (2.2%) | 16 |
| Hyperglycaemic hyperosmolar no | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hyperkalaemia | 39/724 (5.4%) | 45 | 16/724 (2.2%) | 16 |
| Hypermagnesaemia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hypoglycaemia | 19/724 (2.6%) | 21 | 20/724 (2.8%) | 27 |
| Hypokalaemia | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Hyponatraemia | 3/724 (0.4%) | 3 | 5/724 (0.7%) | 6 |
| Hypovolaemia | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Metabolic acidosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Obesity | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Back pain | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Foot deformity | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intervertebral disc degenerati | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Intervertebral disc protrusion | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Muscular weakness | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Musculoskeletal chest pain | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Musculoskeletal pain | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Neck mass | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Osteoarthritis | 6/724 (0.8%) | 6 | 3/724 (0.4%) | 3 |
| Pain in extremity | 1/724 (0.1%) | 1 | 3/724 (0.4%) | 4 |
| Rhabdomyolysis | 1/724 (0.1%) | 1 | 4/724 (0.6%) | 4 |
| Rheumatoid arthritis | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Rotator cuff syndrome | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Spinal column stenosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Systemic lupus erythematosus | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute promyelocytic leukaemia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Adenocarcinoma | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| B-cell lymphoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Bladder cancer | 0/724 (0%) | 0 | 3/724 (0.4%) | 8 |
| Bladder neoplasm | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Bone neoplasm malignant | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Brain neoplasm malignant | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Breast cancer in situ | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Bronchioloalveolar carcinoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Burkitt's lymphoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Colon cancer | 3/724 (0.4%) | 3 | 3/724 (0.4%) | 6 |
| Colon cancer metastatic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hepatic neoplasm malignant | 2/724 (0.3%) | 8 | 0/724 (0%) | 0 |
| Lip and/or oral cavity cancer | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Lung adenocarcinoma | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Lung adenocarcinoma metastatic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Lung cancer metastatic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Lung neoplasm malignant | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Lung squamous cell carcinoma s | 0/724 (0%) | 0 | 2/724 (0.3%) | 4 |
| Lymphoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Malignant ascites | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Metastases to bone | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Metastatic neoplasm | 2/724 (0.3%) | 3 | 0/724 (0%) | 0 |
| Multiple myeloma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Nasopharyngeal cancer stage IV | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Neoplasm | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Neoplasm prostate | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Neuroendocrine carcinoma of th | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Non-small cell lung cancer | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Oesophageal carcinoma | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pancreatic carcinoma | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Pancreatic carcinoma metastati | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Prostate cancer | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Renal cancer metastatic | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Renal cell carcinoma | 3/724 (0.4%) | 5 | 0/724 (0%) | 0 |
| Salivary gland cancer | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Salivary gland neoplasm | 1/724 (0.1%) | 2 | 0/724 (0%) | 0 |
| Sarcoma | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Small cell lung cancer stage u | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Tonsil cancer | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Transitional cell carcinoma | 1/724 (0.1%) | 3 | 0/724 (0%) | 0 |
| Nervous system disorders | ||||
| Altered state of consciousness | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Amnesia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Autonomic nervous system imbal | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Brain stem infarction | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Carotid artery disease | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Carotid artery stenosis | 2/724 (0.3%) | 3 | 4/724 (0.6%) | 4 |
| Central nervous system mass | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cerebellar artery thrombosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Cerebral infarction | 3/724 (0.4%) | 3 | 1/724 (0.1%) | 1 |
| Cerebral ischaemia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cerebral ventricle dilatation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Cerebrovascular accident | 12/724 (1.7%) | 12 | 10/724 (1.4%) | 12 |
| Cognitive disorder | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Convulsion | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Dizziness | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Dizziness postural | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Dysarthria | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Encephalopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Facial paresis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Grand mal convulsion | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Haemorrhage intracranial | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Headache | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Hepatic encephalopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypersomnia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypoaesthesia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypoglycaemic seizure | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypoglycaemic unconsciousness | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intracranial aneurysm | 1/724 (0.1%) | 3 | 1/724 (0.1%) | 1 |
| Ischaemic cerebral infarction | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ischaemic stroke | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Lacunar infarction | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Loss of consciousness | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Metabolic encephalopathy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Nerve root compression | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Neuritis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Parkinson's disease | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Polyneuropathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Presyncope | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Radiculopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Sciatica | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Spondylitic myelopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Syncope | 10/724 (1.4%) | 10 | 9/724 (1.2%) | 10 |
| Thalamic infarction | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Toxic encephalopathy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Transient ischaemic attack | 5/724 (0.7%) | 5 | 10/724 (1.4%) | 12 |
| Tremor | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Psychiatric disorders | ||||
| Adjustment disorder | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Alcohol abuse | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Alcoholism | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Anxiety | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Delirium | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Depression | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Drug abuse | 4/724 (0.6%) | 4 | 1/724 (0.1%) | 1 |
| Major depression | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Mania | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Mental status changes | 5/724 (0.7%) | 5 | 6/724 (0.8%) | 6 |
| Psychotic disorder | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Suicidal ideation | 9/724 (1.2%) | 10 | 2/724 (0.3%) | 2 |
| Suicide attempt | 0/724 (0%) | 0 | 2/724 (0.3%) | 3 |
| Renal and urinary disorders | ||||
| Azotaemia | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Bladder mass | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Calculus ureteric | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Calculus urinary | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Diabetic end stage renal disea | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Haematuria | 2/724 (0.3%) | 3 | 2/724 (0.3%) | 4 |
| Hydronephrosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Nephrolithiasis | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Nephropathy toxic | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Nephrotic syndrome | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Obstructive uropathy | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Polyuria | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Renal disorder | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Renal failure | 3/724 (0.4%) | 3 | 5/724 (0.7%) | 6 |
| Renal failure acute | 130/724 (18%) | 190 | 80/724 (11%) | 105 |
| Renal failure chronic | 4/724 (0.6%) | 5 | 7/724 (1%) | 7 |
| Renal impairment | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Renal mass | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Renal tubular necrosis | 2/724 (0.3%) | 2 | 3/724 (0.4%) | 3 |
| Tubulointerstitial nephritis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Urinary retention | 1/724 (0.1%) | 1 | 3/724 (0.4%) | 3 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Erectile dysfunction | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Prostatitis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 4/724 (0.6%) | 4 | 4/724 (0.6%) | 4 |
| Asthma | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Atelectasis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Bronchial hyperreactivity | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Bronchospasm | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Chronic obstructive pulmonary | 14/724 (1.9%) | 20 | 22/724 (3%) | 39 |
| Cough | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Dyspnoea | 2/724 (0.3%) | 2 | 7/724 (1%) | 9 |
| Dyspnoea exertional | 0/724 (0%) | 0 | 3/724 (0.4%) | 3 |
| Epistaxis | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Haemoptysis | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hypoventilation | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Hypoxia | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Interstitial lung disease | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Lung disorder | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Obstructive airways disorder | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Oropharyngeal pain | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pleural disorder | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pleural effusion | 10/724 (1.4%) | 13 | 4/724 (0.6%) | 5 |
| Pleurisy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pleuritic pain | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pneumonia aspiration | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Pneumonitis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pneumothorax | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pulmonary congestion | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pulmonary embolism | 2/724 (0.3%) | 2 | 4/724 (0.6%) | 4 |
| Pulmonary fibrosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pulmonary haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Pulmonary mass | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Pulmonary oedema | 5/724 (0.7%) | 5 | 8/724 (1.1%) | 8 |
| Respiratory arrest | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Respiratory failure | 5/724 (0.7%) | 6 | 6/724 (0.8%) | 7 |
| Sleep apnoea syndrome | 1/724 (0.1%) | 1 | 2/724 (0.3%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Diabetic foot | 7/724 (1%) | 8 | 10/724 (1.4%) | 12 |
| Diabetic ulcer | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Dry gangrene | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Skin ulcer | 2/724 (0.3%) | 3 | 5/724 (0.7%) | 5 |
| Stasis dermatitis | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Social circumstances | ||||
| Treatment noncompliance | 5/724 (0.7%) | 5 | 4/724 (0.6%) | 4 |
| Surgical and medical procedures | ||||
| Amputation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Appendicectomy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Arteriovenous fistula operatio | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 3 |
| Arthrotomy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Brachytherapy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Carotid endarterectomy | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Chemotherapy | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Coronary arterial stent insert | 1/724 (0.1%) | 1 | 4/724 (0.6%) | 4 |
| Coronary artery bypass | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Drug rehabilitation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Elective surgery | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Ethmoid sinus surgery | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Extubation | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Foot amputation | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastric banding | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Gastric bypass | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Gastrointestinal tube insertio | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Haemodialysis | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Hip arthroplasty | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Knee arthroplasty | 0/724 (0%) | 0 | 2/724 (0.3%) | 2 |
| Leg amputation | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Penile prosthesis insertion | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Rehabilitation therapy | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Therapy regimen changed | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Toe amputation | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Tooth extraction | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Vascular disorders | ||||
| Accelerated hypertension | 2/724 (0.3%) | 2 | 0/724 (0%) | 0 |
| Aneurysm | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Angiodysplasia | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Aortic aneurysm | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Aortic aneurysm rupture | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Aortic arteriosclerosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Aortic stenosis | 2/724 (0.3%) | 2 | 1/724 (0.1%) | 1 |
| Arteriosclerosis | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Arteriovenous fistula | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Deep vein thrombosis | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Embolism | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Femoral arterial stenosis | 2/724 (0.3%) | 3 | 2/724 (0.3%) | 2 |
| Haematoma | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Haemorrhage | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Hypertension | 4/724 (0.6%) | 5 | 6/724 (0.8%) | 6 |
| Hypertensive crisis | 4/724 (0.6%) | 4 | 4/724 (0.6%) | 4 |
| Hypertensive emergency | 3/724 (0.4%) | 3 | 3/724 (0.4%) | 4 |
| Hypotension | 11/724 (1.5%) | 13 | 8/724 (1.1%) | 8 |
| Iliac artery stenosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Intermittent claudication | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Lymphoedema | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Orthostatic hypotension | 1/724 (0.1%) | 3 | 6/724 (0.8%) | 6 |
| Peripheral arterial occlusive | 1/724 (0.1%) | 1 | 1/724 (0.1%) | 1 |
| Peripheral artery aneurysm | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Peripheral embolism | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Peripheral ischaemia | 3/724 (0.4%) | 3 | 0/724 (0%) | 0 |
| Peripheral vascular disorder | 4/724 (0.6%) | 6 | 3/724 (0.4%) | 3 |
| Shock | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Shock haemorrhagic | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Thrombosed varicose vein | 1/724 (0.1%) | 1 | 0/724 (0%) | 0 |
| Thrombosis | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Vascular occlusion | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
| Venous insufficiency | 0/724 (0%) | 0 | 1/724 (0.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Combination of ARB and ACEI | Monotherapy ARB | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/724 (0%) | 0/724 (0%) | ||
Limitations/Caveats
In October, 2012 the DMC recommended that study treatment be stopped primarily because of safety concerns along with low conditional power to detect a treatment effect on the primary outcome.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Linda Fried, MD, MPH |
|---|---|
| Organization | VA Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, PA |
| Phone | 412-360-3930 |
| Linda.Fried@va.gov |
Responsible Party:
US Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00555217
Other Study ID Numbers:
- 565
First Posted:
Nov 8, 2007
Last Update Posted:
May 29, 2015
Last Verified:
May 1, 2015