RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF
Study Details
Study Description
Brief Summary
The purpose of the study was to evaluate the efficacy, safety and tolerability of intravenous infusion of serelaxin, when added to standard therapy, in acute heart failure (AHF) patients.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
This Phase IIIb outcome study in AHF patients was designed as a multicenter, randomized, double-blind, placebo-controlled, event-driven study in order to assess the efficacy, safety and tolerability of intravenous infusion of serelaxin or placebo. The AHF patients randomized to either serelaxin or placebo in the study were followed for a period of 180 days, and were required to receive standard-of-care background HF management during both the index hospitalization and post discharge according to regional or local guidelines/institutional standards.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Serelaxin (RLX030) Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. |
Drug: RLX030
1 mg/mL solution in 6 mL vials
|
Placebo Comparator: Placebo Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Drug: Placebo
Matching placebo solution to serelaxin
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Confirmed Cardiovascular (CV) Death Through Day 180 [180 days]
The percentage of participants with an adjudicated CV death through day 180 was assessed.
- Percentage of Participants With Worsening of Heart Failure (WHF) Through Day 5 [Day 5]
The percentage of participants with WHF through day 5 was assessed.
Secondary Outcome Measures
- Percentage of Participants With All-cause Death Through Day 180 [180 days]
The percentage of participants with all-cause death through day 180 was assessed.
- Length of Total Hospital Stay (LOS) During the Index Acute Heart Failure (AHF) Hospitalization [180 days (Participants still in the hospital at Day 60 were censored at Day 60)]
Length of stay was defined as the index hospitalization discharge date and time minus the baseline date and time plus 1 day.
- Percentage of Participants With First Occurrence of Adjudicated CV Death or Adjudicated Re-hospitalization [180 days]
The percentage of participants with adjudicated CV death or adjudicated re-hospitalization through day 180 was assessed.
- Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization [180 days (Patients still in the hospital at Day 60 were censored at Day 60)]
Length of stay was defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day.
- Percentage of Participants With First Improvement Since Baseline in Congestive Signs and Symptoms of Heart Failure [From baseline to Day 5]
The percentage of participants with first improvement since baseline in congestive signs and symptoms was assessed. The signs and symptoms included exertional dyspnea, orthopnea, rales, jugular venous pressure and peripheral edema/pre-sacral edema.
- Change From Baseline in hsTroponin T Biomarker [Baseline, Day 2, Day 5 and Day 14]
Blood samples were collected to assess the change from baseline in hsTroponin T. The geometric least square mean (LSM) of the ratio of the post-baseline value to the baseline value is presented.
- Change From Baseline in NT-proBNP Biomarker [Baseline, Day 2, Day 5 and Day 14]
Blood samples were collected to assess the change from baseline in NT-proBNP. The ratio of the post-baseline value to the baseline value is presented.
- Change From Baseline in Cystatin C Biomarker [Baseline, Day 2, Day 5 and Day 14]
Blood samples were collected to assess the change from baseline in Cystatin C. The ratio of the post-baseline value to the baseline value is presented.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Male or female 18 years of age, with body weight ≤160 kg
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Hospitalized for AHF with anticipated requirement of IV therapy for at least 48 hours; AHF is defined as including all of the following measured at any time between presentation (including the emergency department) and the end of screening:
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Persistent dyspnea at rest or with minimal exertion
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Pulmonary congestion on chest radiograph
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B-type natriuretic peptide (BNP) ≥500 pg/mL or N-terminal (NT)-proBNP ≥2000 pg/mL; for patients ≥ 75 years of age or with current atrial fibrillation (at the time of randomization), BNP ≥ 750 pg/mL or NT-proBNP ≥ 3,000 pg/mL
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Systolic BP ≥125 mmHg at the start and at the end of screening
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Able to be randomized within 16 hours from presentation to the hospital, including the emergency department
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Received intravenous furosemide of at least 40 mg total (or equivalent) at any time between presentation (this includes outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute HF episode.
Key Exclusion Criteria:
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Dyspnea primarily due to non-cardiac causes
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Known history of respiratory disorders requiring the daily use of IV or oral steroids (does not include inhaled steroids); need for intubation or the current use of IV or oral steroids for chronic obstructive pulmonary disease (COPD)
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Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
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Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
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AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute
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Patients with severe renal impairment defined as pre-randomization estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73m2 calculated using the Simplified Modification of Diet in Renal Disease (sMDRD) equation, and/or those receiving current or planned dialysis or ultrafiltration
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Patients with hematocrit <25%, or a history of blood transfusion within the 14 days prior to screening, or active life-threatening GI bleeding.
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Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed) or history of cirrhosis with evidence of portal hypertension such as varices.
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Significant, uncorrected, left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area <1.0 cm2 or mean gradient >40 mmHg on prior or current echocardiogram), and severe mitral stenosis
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Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.
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Documented, prior to or at the time of randomization, restrictive amyloid myocardiopathy, OR acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does NOT include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Novartis Investigative Site | Huntsville | Alabama | United States | 35801 |
2 | Novartis Investigative Site | Montgomery | Alabama | United States | 36106 |
3 | Novartis Investigative Site | Tucson | Arizona | United States | 85723-0001 |
4 | Novartis Investigative Site | Anaheim | California | United States | 92801 |
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9 | Novartis Investigative Site | Los Angeles | California | United States | 90095 |
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11 | Novartis Investigative Site | Palo Alto | California | United States | 94304-1207 |
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178 | Novartis Investigative Site | Plovdiv | Bulgaria | 4002 | |
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180 | Novartis Investigative Site | Sofia | Bulgaria | 1202 | |
181 | Novartis Investigative Site | Sofia | Bulgaria | 1407 | |
182 | Novartis Investigative Site | Sofia | Bulgaria | 1527 | |
183 | Novartis Investigative Site | Sofia | Bulgaria | 1606 | |
184 | Novartis Investigative Site | Sofia | Bulgaria | 1709 | |
185 | Novartis Investigative Site | Varna | Bulgaria | 9010 | |
186 | Novartis Investigative Site | Calgary | Alberta | Canada | T2N 4Z6 |
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190 | Novartis Investigative Site | Thetford Mines | Quebec | Canada | G6G 2V4 |
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195 | Novartis Investigative Site | Florida Blanca | Colombia | ||
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197 | Novartis Investigative Site | Frydek Mistek | Czech Republic | Czechia | 73801 |
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199 | Novartis Investigative Site | Liberec | Czech Republic | Czechia | 46063 |
200 | Novartis Investigative Site | Pardubice | Czech Republic | Czechia | 532 03 |
201 | Novartis Investigative Site | Praha 6 | Czech Republic | Czechia | 169 02 |
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204 | Novartis Investigative Site | Usti nad Orlici | Czech Republic | Czechia | 562 18 |
205 | Novartis Investigative Site | Zlin | Czech Republic | Czechia | 76275 |
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208 | Novartis Investigative Site | Brno | Czechia | 636 00 | |
209 | Novartis Investigative Site | JIhlava | Czechia | 586 01 | |
210 | Novartis Investigative Site | Kolin | Czechia | 280 20 | |
211 | Novartis Investigative Site | Plzen | Czechia | 301 00 | |
212 | Novartis Investigative Site | Praha 10 | Czechia | 100 34 | |
213 | Novartis Investigative Site | Praha | Czechia | 12808 | |
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217 | Novartis Investigative Site | Randers | Denmark | 8930 | |
218 | Novartis Investigative Site | Amiens | France | 80054 | |
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220 | Novartis Investigative Site | Beziers Cedex | France | 34525 | |
221 | Novartis Investigative Site | Bobigny | France | 93009 | |
222 | Novartis Investigative Site | Caen | France | 14000 | |
223 | Novartis Investigative Site | Chambray-lès-Tours | France | 37170 | |
224 | Novartis Investigative Site | La Tronche | France | 38700 | |
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226 | Novartis Investigative Site | Le Chesnay | France | ||
227 | Novartis Investigative Site | Lille | France | 59037 | |
228 | Novartis Investigative Site | Lille | France | 59042 | |
229 | Novartis Investigative Site | Nancy | France | 54035 | |
230 | Novartis Investigative Site | Paris cedex 10 | France | 75010 | |
231 | Novartis Investigative Site | Paris cedex 18 | France | 75877 | |
232 | Novartis Investigative Site | Paris | France | 75015 | |
233 | Novartis Investigative Site | Pessac cedex | France | 33604 | |
234 | Novartis Investigative Site | Pontoise | France | F-95300 | |
235 | Novartis Investigative Site | Rouen | France | 76000 | |
236 | Novartis Investigative Site | Saint Herblain - Nantes | France | 44093 | |
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241 | Novartis Investigative Site | Berlin | Germany | 10117 | |
242 | Novartis Investigative Site | Berlin | Germany | 12203 | |
243 | Novartis Investigative Site | Berlin | Germany | 12621 | |
244 | Novartis Investigative Site | Berlin | Germany | 13347 | |
245 | Novartis Investigative Site | Berlin | Germany | 13353 | |
246 | Novartis Investigative Site | Berlin | Germany | 13509 | |
247 | Novartis Investigative Site | Berlin | Germany | 13578 | |
248 | Novartis Investigative Site | Bitburg | Germany | 54634 | |
249 | Novartis Investigative Site | Bochum | Germany | 44791 | |
250 | Novartis Investigative Site | Bonn | Germany | 53105 | |
251 | Novartis Investigative Site | Bonn | Germany | 53115 | |
252 | Novartis Investigative Site | Brandenburg | Germany | 16321 | |
253 | Novartis Investigative Site | Bremen | Germany | 28277 | |
254 | Novartis Investigative Site | Coburg | Germany | 96450 | |
255 | Novartis Investigative Site | Detmold | Germany | 32756 | |
256 | Novartis Investigative Site | Dortmund | Germany | 44137 | |
257 | Novartis Investigative Site | Dortmund | Germany | 44379 | |
258 | Novartis Investigative Site | Dresden | Germany | 01067 | |
259 | Novartis Investigative Site | Erfurt | Germany | 99084 | |
260 | Novartis Investigative Site | Erfurt | Germany | 99089 | |
261 | Novartis Investigative Site | Essen | Germany | 45122 | |
262 | Novartis Investigative Site | Essen | Germany | 45356 | |
263 | Novartis Investigative Site | Frankfurt | Germany | 60488 | |
264 | Novartis Investigative Site | Frankfurt | Germany | 60590 | |
265 | Novartis Investigative Site | Frankfurt | Germany | 65929 | |
266 | Novartis Investigative Site | Freiburg | Germany | 79106 | |
267 | Novartis Investigative Site | Friedberg | Germany | 86316 | |
268 | Novartis Investigative Site | Füssen | Germany | 87629 | |
269 | Novartis Investigative Site | Goettingen | Germany | 37075 | |
270 | Novartis Investigative Site | Greifswald | Germany | 17475 | |
271 | Novartis Investigative Site | Göttingen | Germany | 37073 | |
272 | Novartis Investigative Site | Halle Saale | Germany | 06120 | |
273 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
274 | Novartis Investigative Site | Hamburg | Germany | 22291 | |
275 | Novartis Investigative Site | Heilbronn | Germany | 74078 | |
276 | Novartis Investigative Site | Jena | Germany | 07740 | |
277 | Novartis Investigative Site | Kiel | Germany | 24105 | |
278 | Novartis Investigative Site | Kleve | Germany | 47533 | |
279 | Novartis Investigative Site | Koeln-Nippes | Germany | 50733 | |
280 | Novartis Investigative Site | Langen | Germany | 63225 | |
281 | Novartis Investigative Site | Leipzig | Germany | 04103 | |
282 | Novartis Investigative Site | Leverkusen | Germany | 51375 | |
283 | Novartis Investigative Site | Limburg | Germany | 65549 | |
284 | Novartis Investigative Site | Ludwigshafen | Germany | 67063 | |
285 | Novartis Investigative Site | Lübeck | Germany | 23569 | |
286 | Novartis Investigative Site | Magdeburg | Germany | 39104 | |
287 | Novartis Investigative Site | Magdeburg | Germany | 39120 | |
288 | Novartis Investigative Site | Mainz | Germany | 55131 | |
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511 | Novartis Investigative Site | Molndal | Sweden | 431 80 | |
512 | Novartis Investigative Site | Stockholm | Sweden | 17176 | |
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533 | Novartis Investigative Site | Edinburgh | United Kingdom | EH16 4SA | |
534 | Novartis Investigative Site | Glasgow | United Kingdom | G51 4TF | |
535 | Novartis Investigative Site | Kettering | United Kingdom | NN16 8UZ | |
536 | Novartis Investigative Site | Leicester | United Kingdom | LE3 9QP | |
537 | Novartis Investigative Site | Liverpool | United Kingdom | L7 8XP | |
538 | Novartis Investigative Site | Liverpool | United Kingdom | L9 7AL | |
539 | Novartis Investigative Site | London | United Kingdom | SE5 9RS | |
540 | Novartis Investigative Site | Manchester | United Kingdom | M13 9WL | |
541 | Novartis Investigative Site | Portsmouth | United Kingdom | PO6 3LY | |
542 | Novartis Investigative Site | Swindon | United Kingdom | SN3 6BB |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.- CRLX030A2301
- 2013-001498-25
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 6600 participants were randomized into the trial. Only 6545 participants were eligible for analysis. Therefore, the participants flow and baseline characteristics are based on 6545 participants. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Period Title: Overall Study | ||
STARTED | 3274 | 3271 |
Safety Set | 3257 | 3248 |
Full Analysis Set | 3274 | 3271 |
Biomarker Analysis Set | 521 | 510 |
COMPLETED | 3266 | 3262 |
NOT COMPLETED | 8 | 9 |
Baseline Characteristics
Arm/Group Title | Serelaxin (RLX030) | Placebo | Total |
---|---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. | Total of all reporting groups |
Overall Participants | 3274 | 3271 | 6545 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
73.1
(11.24)
|
72.8
(11.17)
|
73.0
(11.20)
|
Sex: Female, Male (Count of Participants) | |||
Female |
1296
39.6%
|
1341
41%
|
2637
40.3%
|
Male |
1978
60.4%
|
1930
59%
|
3908
59.7%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
13
0.4%
|
18
0.6%
|
31
0.5%
|
Asian |
14
0.4%
|
16
0.5%
|
30
0.5%
|
Native Hawaiian or Other Pacific Islander |
4
0.1%
|
4
0.1%
|
8
0.1%
|
Black or African American |
163
5%
|
171
5.2%
|
334
5.1%
|
White |
3017
92.2%
|
2999
91.7%
|
6016
91.9%
|
More than one race |
46
1.4%
|
46
1.4%
|
92
1.4%
|
Unknown or Not Reported |
17
0.5%
|
17
0.5%
|
34
0.5%
|
Outcome Measures
Title | Percentage of Participants With Confirmed Cardiovascular (CV) Death Through Day 180 |
---|---|
Description | The percentage of participants with an adjudicated CV death through day 180 was assessed. |
Time Frame | 180 days |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Number [Percentage of participants] |
8.7
0.3%
|
8.9
0.3%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3857 |
Comments | Adjusted alpha p-value based on multiple testing procedure. | |
Method | Log Rank | |
Comments | One-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.98 | |
Confidence Interval |
(2-Sided) 95% 0.83 to 1.15 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Participants With Worsening of Heart Failure (WHF) Through Day 5 |
---|---|
Description | The percentage of participants with WHF through day 5 was assessed. |
Time Frame | Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Number [Percentage of participants] |
6.9
0.2%
|
7.7
0.2%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0968 |
Comments | Adjusted p-value based on multiple testing procedure | |
Method | Gehan's generalized Wilcoxon test | |
Comments | One-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.89 | |
Confidence Interval |
(2-Sided) 95% 0.75 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Participants With All-cause Death Through Day 180 |
---|---|
Description | The percentage of participants with all-cause death through day 180 was assessed. |
Time Frame | 180 days |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Number [Percentage of participants] |
11.2
0.3%
|
11.9
0.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3890 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.94 | |
Confidence Interval |
(2-Sided) 95% 0.81 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Length of Total Hospital Stay (LOS) During the Index Acute Heart Failure (AHF) Hospitalization |
---|---|
Description | Length of stay was defined as the index hospitalization discharge date and time minus the baseline date and time plus 1 day. |
Time Frame | 180 days (Participants still in the hospital at Day 60 were censored at Day 60) |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Mean (Standard Deviation) [days] |
9.362
(9.3581)
|
9.545
(9.6739)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2204 |
Comments | Based on multiple testing procedure | |
Method | Wilcoxon rank sum test | |
Comments | One-sided p-value |
Title | Percentage of Participants With First Occurrence of Adjudicated CV Death or Adjudicated Re-hospitalization |
---|---|
Description | The percentage of participants with adjudicated CV death or adjudicated re-hospitalization through day 180 was assessed. |
Time Frame | 180 days |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Number [Percentage of participants] |
24.3
0.7%
|
24.9
0.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2744 |
Comments | Adjusted p-value based on multiple testing procedure | |
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 95% 0.88 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization |
---|---|
Description | Length of stay was defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day. |
Time Frame | 180 days (Patients still in the hospital at Day 60 were censored at Day 60) |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3274 | 3271 |
Mean (Standard Deviation) [days] |
3.8
(8.29)
|
4.1
(8.77)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2103 |
Comments | ||
Method | Wilcoxon rank sum test | |
Comments | 2-sided p-value |
Title | Percentage of Participants With First Improvement Since Baseline in Congestive Signs and Symptoms of Heart Failure |
---|---|
Description | The percentage of participants with first improvement since baseline in congestive signs and symptoms was assessed. The signs and symptoms included exertional dyspnea, orthopnea, rales, jugular venous pressure and peripheral edema/pre-sacral edema. |
Time Frame | From baseline to Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set, which included all randomized participants who were not mis-randomized or excluded due to GCP reasons, was considered for the analysis. For each symptom, only participants with observed baseline signs and symptoms and non-missing baseline and post baseline signs and symptoms were analyzed. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 3044 | 3039 |
Exertional dyspnea |
94.1
2.9%
|
92.6
2.8%
|
Orthopnea |
92.9
2.8%
|
91.2
2.8%
|
Rales |
94.1
2.9%
|
93.7
2.9%
|
Jugular venous pressure |
90.4
2.8%
|
88.0
2.7%
|
Peripheral edema, pre-sacral edema |
91.6
2.8%
|
90.7
2.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Exertional dyspnea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0050 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.08 | |
Confidence Interval |
(2-Sided) 95% 1.02 to 1.14 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Orthopnea | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0051 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.08 | |
Confidence Interval |
(2-Sided) 95% 1.02 to 1.14 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Rales | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.9962 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.00 | |
Confidence Interval |
(2-Sided) 95% 0.95 to 1.05 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Jugular venous pressure | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0196 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.08 | |
Confidence Interval |
(2-Sided) 95% 1.01 to 1.15 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Peripheral edema, pre-sacral edema | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2158 |
Comments | ||
Method | Log Rank | |
Comments | 2-sided p-value | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.04 | |
Confidence Interval |
(2-Sided) 95% 0.98 to 1.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in hsTroponin T Biomarker |
---|---|
Description | Blood samples were collected to assess the change from baseline in hsTroponin T. The geometric least square mean (LSM) of the ratio of the post-baseline value to the baseline value is presented. |
Time Frame | Baseline, Day 2, Day 5 and Day 14 |
Outcome Measure Data
Analysis Population Description |
---|
Participants from the biomarker analysis set, who had both baseline and post baseline values for a given time point, were analyzed at that time point. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 521 | 510 |
Day 2 |
0.9808
|
1.0432
|
Day 5 |
0.9589
|
1.0678
|
Day 14 |
0.7813
|
0.8611
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 2 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0209 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9401 | |
Confidence Interval |
(2-Sided) 95% 0.8921 to 0.9907 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 5 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0034 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.8980 | |
Confidence Interval |
(2-Sided) 95% 0.8358 to 0.9649 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 14 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0209 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9074 | |
Confidence Interval |
(2-Sided) 95% 0.8355 to 0.9854 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in NT-proBNP Biomarker |
---|---|
Description | Blood samples were collected to assess the change from baseline in NT-proBNP. The ratio of the post-baseline value to the baseline value is presented. |
Time Frame | Baseline, Day 2, Day 5 and Day 14 |
Outcome Measure Data
Analysis Population Description |
---|
Participants from the biomarker analysis set, who had both baseline and post baseline values for a given time point, were analyzed at that time point. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 521 | 510 |
Day 2 |
0.4902
|
0.5702
|
Day 5 |
0.4249
|
0.4454
|
Day 14 |
0.4265
|
0.4469
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 2 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0007 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.8597 | |
Confidence Interval |
(2-Sided) 95% 0.7876 to 0.9385 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 5 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3709 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9539 | |
Confidence Interval |
(2-Sided) 95% 0.8600 to 1.0579 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 14 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3893 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9543 | |
Confidence Interval |
(2-Sided) 95% 0.8578 to 1.0617 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Cystatin C Biomarker |
---|---|
Description | Blood samples were collected to assess the change from baseline in Cystatin C. The ratio of the post-baseline value to the baseline value is presented. |
Time Frame | Baseline, Day 2, Day 5 and Day 14 |
Outcome Measure Data
Analysis Population Description |
---|
Participants from the biomarker analysis set, who had both baseline and post baseline values for a given time point, were analyzed at that time point. |
Arm/Group Title | Serelaxin (RLX030) | Placebo |
---|---|---|
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. |
Measure Participants | 521 | 510 |
Day 2 |
1.0261
|
1.0648
|
Day 5 |
1.1171
|
1.1259
|
Day 14 |
1.1186
|
1.1342
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 2 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9637 | |
Confidence Interval |
(2-Sided) 95% 0.9447 to 0.9830 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 5 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5361 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9922 | |
Confidence Interval |
(2-Sided) 95% 0.9677 to 1.0172 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Serelaxin (RLX030), Placebo |
---|---|---|
Comments | Day 14 | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3750 |
Comments | ||
Method | Repeated measures model | |
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of RLX030 to placebo |
Estimated Value | 0.9863 | |
Confidence Interval |
(2-Sided) 95% 0.9567 to 1.0169 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | up to 180 days | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Serelaxin (RLX030) | Placebo | ||
Arm/Group Description | Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours. | Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours. | ||
All Cause Mortality |
||||
Serelaxin (RLX030) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 363/3257 (11.1%) | 386/3248 (11.9%) | ||
Serious Adverse Events |
||||
Serelaxin (RLX030) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 412/3257 (12.6%) | 424/3248 (13.1%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 7/3257 (0.2%) | 7/3248 (0.2%) | ||
Anaemia macrocytic | 1/3257 (0%) | 0/3248 (0%) | ||
Haemorrhagic anaemia | 0/3257 (0%) | 1/3248 (0%) | ||
Heparin-induced thrombocytopenia | 0/3257 (0%) | 1/3248 (0%) | ||
Leukocytosis | 0/3257 (0%) | 1/3248 (0%) | ||
Leukopenia | 1/3257 (0%) | 0/3248 (0%) | ||
Lymphadenopathy | 0/3257 (0%) | 1/3248 (0%) | ||
Cardiac disorders | ||||
Acute coronary syndrome | 1/3257 (0%) | 3/3248 (0.1%) | ||
Acute left ventricular failure | 1/3257 (0%) | 0/3248 (0%) | ||
Acute myocardial infarction | 14/3257 (0.4%) | 12/3248 (0.4%) | ||
Angina pectoris | 1/3257 (0%) | 7/3248 (0.2%) | ||
Angina unstable | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Aortic valve incompetence | 1/3257 (0%) | 2/3248 (0.1%) | ||
Aortic valve stenosis | 4/3257 (0.1%) | 9/3248 (0.3%) | ||
Arrhythmia | 0/3257 (0%) | 2/3248 (0.1%) | ||
Arteriosclerosis coronary artery | 2/3257 (0.1%) | 0/3248 (0%) | ||
Atrial fibrillation | 10/3257 (0.3%) | 13/3248 (0.4%) | ||
Atrial flutter | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Atrial thrombosis | 0/3257 (0%) | 1/3248 (0%) | ||
Atrioventricular block | 1/3257 (0%) | 0/3248 (0%) | ||
Atrioventricular block complete | 5/3257 (0.2%) | 2/3248 (0.1%) | ||
Atrioventricular block second degree | 0/3257 (0%) | 1/3248 (0%) | ||
Atrioventricular dissociation | 1/3257 (0%) | 0/3248 (0%) | ||
Bradyarrhythmia | 1/3257 (0%) | 1/3248 (0%) | ||
Bradycardia | 4/3257 (0.1%) | 4/3248 (0.1%) | ||
Cardiac arrest | 4/3257 (0.1%) | 9/3248 (0.3%) | ||
Cardiac failure | 62/3257 (1.9%) | 68/3248 (2.1%) | ||
Cardiac failure acute | 14/3257 (0.4%) | 8/3248 (0.2%) | ||
Cardiac failure chronic | 2/3257 (0.1%) | 3/3248 (0.1%) | ||
Cardiac failure congestive | 12/3257 (0.4%) | 9/3248 (0.3%) | ||
Cardio-respiratory arrest | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Cardiogenic shock | 5/3257 (0.2%) | 6/3248 (0.2%) | ||
Cardiopulmonary failure | 1/3257 (0%) | 0/3248 (0%) | ||
Cardiorenal syndrome | 1/3257 (0%) | 2/3248 (0.1%) | ||
Chordae tendinae rupture | 2/3257 (0.1%) | 1/3248 (0%) | ||
Congestive cardiomyopathy | 0/3257 (0%) | 2/3248 (0.1%) | ||
Coronary artery disease | 17/3257 (0.5%) | 12/3248 (0.4%) | ||
Coronary artery occlusion | 1/3257 (0%) | 1/3248 (0%) | ||
Coronary artery perforation | 1/3257 (0%) | 0/3248 (0%) | ||
Coronary artery stenosis | 5/3257 (0.2%) | 2/3248 (0.1%) | ||
Defect conduction intraventricular | 0/3257 (0%) | 1/3248 (0%) | ||
Ischaemic cardiomyopathy | 1/3257 (0%) | 0/3248 (0%) | ||
Left ventricular dysfunction | 2/3257 (0.1%) | 0/3248 (0%) | ||
Mitral valve incompetence | 5/3257 (0.2%) | 5/3248 (0.2%) | ||
Mitral valve stenosis | 0/3257 (0%) | 1/3248 (0%) | ||
Myocardial infarction | 3/3257 (0.1%) | 4/3248 (0.1%) | ||
Myocardial ischaemia | 2/3257 (0.1%) | 3/3248 (0.1%) | ||
Pericarditis | 0/3257 (0%) | 1/3248 (0%) | ||
Sinus bradycardia | 1/3257 (0%) | 2/3248 (0.1%) | ||
Sinus node dysfunction | 1/3257 (0%) | 2/3248 (0.1%) | ||
Supraventricular tachycardia | 1/3257 (0%) | 2/3248 (0.1%) | ||
Tachyarrhythmia | 0/3257 (0%) | 1/3248 (0%) | ||
Tachycardia | 1/3257 (0%) | 0/3248 (0%) | ||
Torsade de pointes | 1/3257 (0%) | 0/3248 (0%) | ||
Ventricular arrhythmia | 1/3257 (0%) | 1/3248 (0%) | ||
Ventricular fibrillation | 4/3257 (0.1%) | 6/3248 (0.2%) | ||
Ventricular tachycardia | 14/3257 (0.4%) | 11/3248 (0.3%) | ||
Endocrine disorders | ||||
Hyperthyroidism | 0/3257 (0%) | 1/3248 (0%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 2/3257 (0.1%) | 0/3248 (0%) | ||
Ascites | 1/3257 (0%) | 0/3248 (0%) | ||
Colitis | 0/3257 (0%) | 1/3248 (0%) | ||
Diarrhoea | 1/3257 (0%) | 0/3248 (0%) | ||
Duodenal ulcer haemorrhage | 1/3257 (0%) | 1/3248 (0%) | ||
Dyspepsia | 0/3257 (0%) | 1/3248 (0%) | ||
Enterocolitis | 0/3257 (0%) | 1/3248 (0%) | ||
Gastritis | 1/3257 (0%) | 0/3248 (0%) | ||
Gastritis erosive | 1/3257 (0%) | 0/3248 (0%) | ||
Gastroduodenal ulcer | 1/3257 (0%) | 0/3248 (0%) | ||
Gastrointestinal haemorrhage | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Haematochezia | 1/3257 (0%) | 0/3248 (0%) | ||
Ileus | 2/3257 (0.1%) | 0/3248 (0%) | ||
Ileus paralytic | 0/3257 (0%) | 1/3248 (0%) | ||
Inguinal hernia | 1/3257 (0%) | 1/3248 (0%) | ||
Intestinal stenosis | 0/3257 (0%) | 1/3248 (0%) | ||
Large intestinal haemorrhage | 0/3257 (0%) | 1/3248 (0%) | ||
Large intestine polyp | 1/3257 (0%) | 0/3248 (0%) | ||
Melaena | 1/3257 (0%) | 0/3248 (0%) | ||
Pancreatitis | 0/3257 (0%) | 1/3248 (0%) | ||
Peritoneal haemorrhage | 0/3257 (0%) | 1/3248 (0%) | ||
Rectal haemorrhage | 1/3257 (0%) | 1/3248 (0%) | ||
Retroperitoneal haemorrhage | 1/3257 (0%) | 0/3248 (0%) | ||
Small intestinal obstruction | 0/3257 (0%) | 1/3248 (0%) | ||
Subileus | 0/3257 (0%) | 1/3248 (0%) | ||
Vomiting | 1/3257 (0%) | 0/3248 (0%) | ||
General disorders | ||||
Asthenia | 0/3257 (0%) | 1/3248 (0%) | ||
Cardiac death | 0/3257 (0%) | 2/3248 (0.1%) | ||
Drug effect increased | 1/3257 (0%) | 0/3248 (0%) | ||
Extravasation | 0/3257 (0%) | 1/3248 (0%) | ||
Fatigue | 0/3257 (0%) | 1/3248 (0%) | ||
General physical health deterioration | 1/3257 (0%) | 0/3248 (0%) | ||
Inflammation | 1/3257 (0%) | 0/3248 (0%) | ||
Infusion site phlebitis | 0/3257 (0%) | 1/3248 (0%) | ||
Multiple organ dysfunction syndrome | 4/3257 (0.1%) | 1/3248 (0%) | ||
Non-cardiac chest pain | 2/3257 (0.1%) | 0/3248 (0%) | ||
Pyrexia | 0/3257 (0%) | 1/3248 (0%) | ||
Sudden cardiac death | 3/3257 (0.1%) | 6/3248 (0.2%) | ||
Sudden death | 0/3257 (0%) | 1/3248 (0%) | ||
Vascular stent occlusion | 0/3257 (0%) | 1/3248 (0%) | ||
Hepatobiliary disorders | ||||
Alcoholic liver disease | 0/3257 (0%) | 1/3248 (0%) | ||
Drug-induced liver injury | 0/3257 (0%) | 1/3248 (0%) | ||
Hepatic congestion | 1/3257 (0%) | 0/3248 (0%) | ||
Hepatic failure | 2/3257 (0.1%) | 3/3248 (0.1%) | ||
Hepatic function abnormal | 1/3257 (0%) | 0/3248 (0%) | ||
Hepatocellular injury | 2/3257 (0.1%) | 1/3248 (0%) | ||
Hyperbilirubinaemia | 0/3257 (0%) | 1/3248 (0%) | ||
Jaundice | 1/3257 (0%) | 0/3248 (0%) | ||
Liver injury | 1/3257 (0%) | 1/3248 (0%) | ||
Immune system disorders | ||||
Hypersensitivity | 1/3257 (0%) | 0/3248 (0%) | ||
Infections and infestations | ||||
Abdominal abscess | 1/3257 (0%) | 0/3248 (0%) | ||
Appendicitis | 0/3257 (0%) | 1/3248 (0%) | ||
Arthritis bacterial | 1/3257 (0%) | 0/3248 (0%) | ||
Aspergilloma | 0/3257 (0%) | 1/3248 (0%) | ||
Bacteraemia | 0/3257 (0%) | 1/3248 (0%) | ||
Bronchitis | 9/3257 (0.3%) | 4/3248 (0.1%) | ||
Cellulitis | 0/3257 (0%) | 1/3248 (0%) | ||
Cholecystitis infective | 1/3257 (0%) | 0/3248 (0%) | ||
Chronic hepatitis B | 1/3257 (0%) | 0/3248 (0%) | ||
Clostridium difficile infection | 1/3257 (0%) | 1/3248 (0%) | ||
Cystitis | 3/3257 (0.1%) | 1/3248 (0%) | ||
Cystitis bacterial | 0/3257 (0%) | 1/3248 (0%) | ||
Device related infection | 0/3257 (0%) | 1/3248 (0%) | ||
Diverticulitis | 0/3257 (0%) | 1/3248 (0%) | ||
Enterocolitis bacterial | 0/3257 (0%) | 1/3248 (0%) | ||
Erysipelas | 1/3257 (0%) | 0/3248 (0%) | ||
Gastroenteritis | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Gastroenteritis clostridial | 0/3257 (0%) | 1/3248 (0%) | ||
Influenza | 1/3257 (0%) | 0/3248 (0%) | ||
Intervertebral discitis | 0/3257 (0%) | 1/3248 (0%) | ||
Lower respiratory tract infection | 2/3257 (0.1%) | 0/3248 (0%) | ||
Nasopharyngitis | 0/3257 (0%) | 1/3248 (0%) | ||
Nosocomial infection | 1/3257 (0%) | 0/3248 (0%) | ||
Orchitis | 0/3257 (0%) | 1/3248 (0%) | ||
Pharyngitis | 1/3257 (0%) | 0/3248 (0%) | ||
Pneumococcal sepsis | 1/3257 (0%) | 0/3248 (0%) | ||
Pneumonia | 34/3257 (1%) | 32/3248 (1%) | ||
Pneumonia streptococcal | 1/3257 (0%) | 0/3248 (0%) | ||
Pulmonary sepsis | 1/3257 (0%) | 1/3248 (0%) | ||
Pyelonephritis | 0/3257 (0%) | 1/3248 (0%) | ||
Respiratory tract infection | 0/3257 (0%) | 1/3248 (0%) | ||
Sepsis | 6/3257 (0.2%) | 8/3248 (0.2%) | ||
Septic shock | 4/3257 (0.1%) | 2/3248 (0.1%) | ||
Staphylococcal bacteraemia | 2/3257 (0.1%) | 3/3248 (0.1%) | ||
Staphylococcal infection | 0/3257 (0%) | 1/3248 (0%) | ||
Streptococcal bacteraemia | 1/3257 (0%) | 0/3248 (0%) | ||
Streptococcal sepsis | 1/3257 (0%) | 0/3248 (0%) | ||
Urinary tract infection | 13/3257 (0.4%) | 5/3248 (0.2%) | ||
Urinary tract infection pseudomonal | 0/3257 (0%) | 1/3248 (0%) | ||
Urosepsis | 1/3257 (0%) | 3/3248 (0.1%) | ||
Injury, poisoning and procedural complications | ||||
Aortic restenosis | 1/3257 (0%) | 0/3248 (0%) | ||
Cardiac valve replacement complication | 0/3257 (0%) | 1/3248 (0%) | ||
Coronary artery restenosis | 2/3257 (0.1%) | 1/3248 (0%) | ||
Facial bones fracture | 0/3257 (0%) | 1/3248 (0%) | ||
Fall | 1/3257 (0%) | 0/3248 (0%) | ||
Femoral neck fracture | 2/3257 (0.1%) | 0/3248 (0%) | ||
Lumbar vertebral fracture | 2/3257 (0.1%) | 0/3248 (0%) | ||
Post procedural myocardial infarction | 1/3257 (0%) | 0/3248 (0%) | ||
Procedural complication | 1/3257 (0%) | 0/3248 (0%) | ||
Procedural hypotension | 1/3257 (0%) | 0/3248 (0%) | ||
Procedural pneumothorax | 0/3257 (0%) | 1/3248 (0%) | ||
Rib fracture | 1/3257 (0%) | 0/3248 (0%) | ||
Subdural haematoma | 0/3257 (0%) | 2/3248 (0.1%) | ||
Toxicity to various agents | 1/3257 (0%) | 0/3248 (0%) | ||
Vascular pseudoaneurysm | 0/3257 (0%) | 2/3248 (0.1%) | ||
Investigations | ||||
Aspartate aminotransferase increased | 1/3257 (0%) | 0/3248 (0%) | ||
Blood bilirubin increased | 2/3257 (0.1%) | 0/3248 (0%) | ||
Blood creatinine increased | 1/3257 (0%) | 2/3248 (0.1%) | ||
Blood pressure decreased | 0/3257 (0%) | 2/3248 (0.1%) | ||
C-reactive protein increased | 1/3257 (0%) | 1/3248 (0%) | ||
Cardiac output decreased | 1/3257 (0%) | 0/3248 (0%) | ||
Ejection fraction decreased | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Electrocardiogram T wave inversion | 0/3257 (0%) | 1/3248 (0%) | ||
Haemoglobin decreased | 0/3257 (0%) | 1/3248 (0%) | ||
Hepatic enzyme increased | 3/3257 (0.1%) | 1/3248 (0%) | ||
Liver function test increased | 0/3257 (0%) | 1/3248 (0%) | ||
Oxygen saturation decreased | 1/3257 (0%) | 0/3248 (0%) | ||
Troponin increased | 1/3257 (0%) | 1/3248 (0%) | ||
Vascular resistance pulmonary increased | 1/3257 (0%) | 0/3248 (0%) | ||
Metabolism and nutrition disorders | ||||
Dehydration | 3/3257 (0.1%) | 1/3248 (0%) | ||
Diabetes mellitus | 0/3257 (0%) | 1/3248 (0%) | ||
Gout | 1/3257 (0%) | 1/3248 (0%) | ||
Hyperkalaemia | 3/3257 (0.1%) | 2/3248 (0.1%) | ||
Hypoglycaemia | 1/3257 (0%) | 2/3248 (0.1%) | ||
Hypokalaemia | 1/3257 (0%) | 1/3248 (0%) | ||
Hyponatraemia | 1/3257 (0%) | 0/3248 (0%) | ||
Hypovolaemia | 1/3257 (0%) | 0/3248 (0%) | ||
Lactic acidosis | 0/3257 (0%) | 1/3248 (0%) | ||
Metabolic acidosis | 1/3257 (0%) | 0/3248 (0%) | ||
Metabolic alkalosis | 0/3257 (0%) | 1/3248 (0%) | ||
Type 2 diabetes mellitus | 0/3257 (0%) | 1/3248 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Facial asymmetry | 0/3257 (0%) | 1/3248 (0%) | ||
Joint effusion | 1/3257 (0%) | 0/3248 (0%) | ||
Muscle haemorrhage | 2/3257 (0.1%) | 0/3248 (0%) | ||
Muscle spasms | 1/3257 (0%) | 0/3248 (0%) | ||
Musculoskeletal chest pain | 1/3257 (0%) | 0/3248 (0%) | ||
Myositis | 1/3257 (0%) | 0/3248 (0%) | ||
Pain in extremity | 0/3257 (0%) | 1/3248 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Bladder transitional cell carcinoma | 1/3257 (0%) | 0/3248 (0%) | ||
Breast cancer | 0/3257 (0%) | 1/3248 (0%) | ||
Colon neoplasm | 1/3257 (0%) | 0/3248 (0%) | ||
Colorectal adenocarcinoma | 0/3257 (0%) | 1/3248 (0%) | ||
Gastric cancer | 0/3257 (0%) | 1/3248 (0%) | ||
Lung adenocarcinoma | 1/3257 (0%) | 0/3248 (0%) | ||
Lung adenocarcinoma metastatic | 0/3257 (0%) | 1/3248 (0%) | ||
Lung neoplasm malignant | 1/3257 (0%) | 2/3248 (0.1%) | ||
Mediastinum neoplasm | 0/3257 (0%) | 1/3248 (0%) | ||
Mesothelioma | 0/3257 (0%) | 1/3248 (0%) | ||
Metastases to liver | 0/3257 (0%) | 1/3248 (0%) | ||
Metastases to lung | 0/3257 (0%) | 1/3248 (0%) | ||
Metastatic gastric cancer | 0/3257 (0%) | 1/3248 (0%) | ||
Myelodysplastic syndrome | 1/3257 (0%) | 0/3248 (0%) | ||
Ovarian neoplasm | 0/3257 (0%) | 1/3248 (0%) | ||
Prostate cancer | 1/3257 (0%) | 0/3248 (0%) | ||
Renal neoplasm | 0/3257 (0%) | 1/3248 (0%) | ||
Small cell lung cancer | 0/3257 (0%) | 1/3248 (0%) | ||
Waldenstrom's macroglobulinaemia | 1/3257 (0%) | 0/3248 (0%) | ||
Nervous system disorders | ||||
Altered state of consciousness | 1/3257 (0%) | 0/3248 (0%) | ||
Aphasia | 1/3257 (0%) | 1/3248 (0%) | ||
Brain stem stroke | 0/3257 (0%) | 1/3248 (0%) | ||
Carotid artery stenosis | 0/3257 (0%) | 1/3248 (0%) | ||
Carotid sinus syndrome | 1/3257 (0%) | 1/3248 (0%) | ||
Cerebral artery embolism | 0/3257 (0%) | 1/3248 (0%) | ||
Cerebral infarction | 1/3257 (0%) | 1/3248 (0%) | ||
Cerebrovascular accident | 2/3257 (0.1%) | 3/3248 (0.1%) | ||
Cognitive disorder | 0/3257 (0%) | 1/3248 (0%) | ||
Dementia | 0/3257 (0%) | 1/3248 (0%) | ||
Dizziness | 1/3257 (0%) | 1/3248 (0%) | ||
Embolic stroke | 1/3257 (0%) | 1/3248 (0%) | ||
Epilepsy | 1/3257 (0%) | 0/3248 (0%) | ||
Haemorrhage intracranial | 0/3257 (0%) | 1/3248 (0%) | ||
Hemiparesis | 0/3257 (0%) | 1/3248 (0%) | ||
Hypercapnic coma | 0/3257 (0%) | 1/3248 (0%) | ||
Ischaemic cerebral infarction | 1/3257 (0%) | 0/3248 (0%) | ||
Ischaemic stroke | 11/3257 (0.3%) | 16/3248 (0.5%) | ||
Loss of consciousness | 1/3257 (0%) | 0/3248 (0%) | ||
Muscle contractions involuntary | 1/3257 (0%) | 0/3248 (0%) | ||
Neuropathy peripheral | 1/3257 (0%) | 0/3248 (0%) | ||
Presyncope | 2/3257 (0.1%) | 0/3248 (0%) | ||
Radiculopathy | 1/3257 (0%) | 0/3248 (0%) | ||
Seizure | 2/3257 (0.1%) | 0/3248 (0%) | ||
Somnolence | 1/3257 (0%) | 1/3248 (0%) | ||
Syncope | 5/3257 (0.2%) | 3/3248 (0.1%) | ||
Transient ischaemic attack | 6/3257 (0.2%) | 1/3248 (0%) | ||
Vascular encephalopathy | 1/3257 (0%) | 0/3248 (0%) | ||
Product Issues | ||||
Device battery issue | 1/3257 (0%) | 0/3248 (0%) | ||
Device leakage | 1/3257 (0%) | 0/3248 (0%) | ||
Device malfunction | 0/3257 (0%) | 1/3248 (0%) | ||
Psychiatric disorders | ||||
Acute psychosis | 0/3257 (0%) | 1/3248 (0%) | ||
Confusional state | 2/3257 (0.1%) | 1/3248 (0%) | ||
Delirium | 2/3257 (0.1%) | 2/3248 (0.1%) | ||
Delirium tremens | 1/3257 (0%) | 0/3248 (0%) | ||
Suicidal ideation | 0/3257 (0%) | 1/3248 (0%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 20/3257 (0.6%) | 25/3248 (0.8%) | ||
Anuria | 2/3257 (0.1%) | 0/3248 (0%) | ||
Azotaemia | 1/3257 (0%) | 0/3248 (0%) | ||
Chronic kidney disease | 4/3257 (0.1%) | 3/3248 (0.1%) | ||
Haematuria | 1/3257 (0%) | 1/3248 (0%) | ||
Nephropathy toxic | 0/3257 (0%) | 6/3248 (0.2%) | ||
Nephrotic syndrome | 1/3257 (0%) | 1/3248 (0%) | ||
Oliguria | 1/3257 (0%) | 1/3248 (0%) | ||
Prerenal failure | 1/3257 (0%) | 0/3248 (0%) | ||
Renal artery stenosis | 0/3257 (0%) | 1/3248 (0%) | ||
Renal failure | 10/3257 (0.3%) | 16/3248 (0.5%) | ||
Renal impairment | 13/3257 (0.4%) | 9/3248 (0.3%) | ||
Renal mass | 0/3257 (0%) | 1/3248 (0%) | ||
Urinary retention | 1/3257 (0%) | 0/3248 (0%) | ||
Reproductive system and breast disorders | ||||
Acquired phimosis | 0/3257 (0%) | 1/3248 (0%) | ||
Benign prostatic hyperplasia | 0/3257 (0%) | 1/3248 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Acute pulmonary oedema | 5/3257 (0.2%) | 5/3248 (0.2%) | ||
Acute respiratory distress syndrome | 1/3257 (0%) | 1/3248 (0%) | ||
Acute respiratory failure | 3/3257 (0.1%) | 3/3248 (0.1%) | ||
Bronchitis chronic | 0/3257 (0%) | 1/3248 (0%) | ||
Bronchospasm | 1/3257 (0%) | 1/3248 (0%) | ||
Chronic obstructive pulmonary disease | 5/3257 (0.2%) | 7/3248 (0.2%) | ||
Dyspnoea | 6/3257 (0.2%) | 5/3248 (0.2%) | ||
Dyspnoea exertional | 0/3257 (0%) | 1/3248 (0%) | ||
Epistaxis | 0/3257 (0%) | 1/3248 (0%) | ||
Haemothorax | 1/3257 (0%) | 0/3248 (0%) | ||
Hypercapnia | 0/3257 (0%) | 1/3248 (0%) | ||
Hypoxia | 1/3257 (0%) | 2/3248 (0.1%) | ||
Interstitial lung disease | 1/3257 (0%) | 1/3248 (0%) | ||
Lung infiltration | 0/3257 (0%) | 1/3248 (0%) | ||
Pleural effusion | 5/3257 (0.2%) | 2/3248 (0.1%) | ||
Pneumothorax | 0/3257 (0%) | 2/3248 (0.1%) | ||
Pulmonary cavitation | 0/3257 (0%) | 1/3248 (0%) | ||
Pulmonary embolism | 5/3257 (0.2%) | 7/3248 (0.2%) | ||
Pulmonary fibrosis | 1/3257 (0%) | 1/3248 (0%) | ||
Pulmonary hypertension | 1/3257 (0%) | 1/3248 (0%) | ||
Pulmonary mass | 0/3257 (0%) | 1/3248 (0%) | ||
Pulmonary oedema | 3/3257 (0.1%) | 2/3248 (0.1%) | ||
Respiratory acidosis | 0/3257 (0%) | 1/3248 (0%) | ||
Respiratory arrest | 0/3257 (0%) | 1/3248 (0%) | ||
Respiratory depression | 0/3257 (0%) | 1/3248 (0%) | ||
Respiratory distress | 1/3257 (0%) | 0/3248 (0%) | ||
Respiratory failure | 7/3257 (0.2%) | 10/3248 (0.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Diabetic foot | 0/3257 (0%) | 1/3248 (0%) | ||
Drug eruption | 1/3257 (0%) | 0/3248 (0%) | ||
Panniculitis | 1/3257 (0%) | 0/3248 (0%) | ||
Rash maculo-papular | 0/3257 (0%) | 1/3248 (0%) | ||
Skin ulcer | 0/3257 (0%) | 2/3248 (0.1%) | ||
Surgical and medical procedures | ||||
Cardioversion | 1/3257 (0%) | 0/3248 (0%) | ||
Coronary artery bypass | 1/3257 (0%) | 0/3248 (0%) | ||
Toe amputation | 0/3257 (0%) | 1/3248 (0%) | ||
Vascular disorders | ||||
Aortic aneurysm | 0/3257 (0%) | 1/3248 (0%) | ||
Aortic aneurysm rupture | 1/3257 (0%) | 0/3248 (0%) | ||
Aortic dissection | 1/3257 (0%) | 0/3248 (0%) | ||
Arterial stenosis | 0/3257 (0%) | 1/3248 (0%) | ||
Arteriosclerosis | 0/3257 (0%) | 2/3248 (0.1%) | ||
Arteriovenous fistula | 0/3257 (0%) | 1/3248 (0%) | ||
Deep vein thrombosis | 0/3257 (0%) | 1/3248 (0%) | ||
Hypertension | 1/3257 (0%) | 3/3248 (0.1%) | ||
Hypertensive crisis | 3/3257 (0.1%) | 1/3248 (0%) | ||
Hypotension | 14/3257 (0.4%) | 9/3248 (0.3%) | ||
Hypovolaemic shock | 0/3257 (0%) | 1/3248 (0%) | ||
Iliac artery embolism | 1/3257 (0%) | 0/3248 (0%) | ||
Orthostatic hypotension | 0/3257 (0%) | 1/3248 (0%) | ||
Peripheral embolism | 1/3257 (0%) | 0/3248 (0%) | ||
Peripheral vascular disorder | 0/3257 (0%) | 1/3248 (0%) | ||
Phlebitis | 0/3257 (0%) | 1/3248 (0%) | ||
Shock | 1/3257 (0%) | 0/3248 (0%) | ||
Subclavian steal syndrome | 1/3257 (0%) | 0/3248 (0%) | ||
Thrombophlebitis | 0/3257 (0%) | 1/3248 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Serelaxin (RLX030) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1336/3257 (41%) | 1277/3248 (39.3%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 48/3257 (1.5%) | 47/3248 (1.4%) | ||
Cardiac disorders | ||||
Angina pectoris | 17/3257 (0.5%) | 15/3248 (0.5%) | ||
Aortic valve incompetence | 21/3257 (0.6%) | 25/3248 (0.8%) | ||
Aortic valve stenosis | 23/3257 (0.7%) | 13/3248 (0.4%) | ||
Atrial fibrillation | 46/3257 (1.4%) | 45/3248 (1.4%) | ||
Bradycardia | 23/3257 (0.7%) | 22/3248 (0.7%) | ||
Cardiac failure | 162/3257 (5%) | 185/3248 (5.7%) | ||
Mitral valve incompetence | 52/3257 (1.6%) | 47/3248 (1.4%) | ||
Tricuspid valve incompetence | 30/3257 (0.9%) | 21/3248 (0.6%) | ||
Ventricular tachycardia | 37/3257 (1.1%) | 24/3248 (0.7%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 18/3257 (0.6%) | 19/3248 (0.6%) | ||
Constipation | 70/3257 (2.1%) | 57/3248 (1.8%) | ||
Diarrhoea | 44/3257 (1.4%) | 52/3248 (1.6%) | ||
Nausea | 59/3257 (1.8%) | 51/3248 (1.6%) | ||
Vomiting | 30/3257 (0.9%) | 24/3248 (0.7%) | ||
General disorders | ||||
Non-cardiac chest pain | 12/3257 (0.4%) | 20/3248 (0.6%) | ||
Pyrexia | 31/3257 (1%) | 41/3248 (1.3%) | ||
Infections and infestations | ||||
Bronchitis | 30/3257 (0.9%) | 47/3248 (1.4%) | ||
Cystitis | 18/3257 (0.6%) | 7/3248 (0.2%) | ||
Pneumonia | 17/3257 (0.5%) | 22/3248 (0.7%) | ||
Urinary tract infection | 58/3257 (1.8%) | 68/3248 (2.1%) | ||
Investigations | ||||
Blood creatinine increased | 36/3257 (1.1%) | 49/3248 (1.5%) | ||
Blood potassium decreased | 15/3257 (0.5%) | 20/3248 (0.6%) | ||
Blood pressure decreased | 36/3257 (1.1%) | 23/3248 (0.7%) | ||
Blood pressure systolic decreased | 29/3257 (0.9%) | 24/3248 (0.7%) | ||
Blood urea increased | 24/3257 (0.7%) | 25/3248 (0.8%) | ||
Metabolism and nutrition disorders | ||||
Gout | 16/3257 (0.5%) | 28/3248 (0.9%) | ||
Hyperglycaemia | 25/3257 (0.8%) | 17/3248 (0.5%) | ||
Hyperkalaemia | 40/3257 (1.2%) | 36/3248 (1.1%) | ||
Hyperuricaemia | 25/3257 (0.8%) | 21/3248 (0.6%) | ||
Hypoglycaemia | 29/3257 (0.9%) | 22/3248 (0.7%) | ||
Hypokalaemia | 263/3257 (8.1%) | 241/3248 (7.4%) | ||
Hyponatraemia | 19/3257 (0.6%) | 13/3248 (0.4%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 25/3257 (0.8%) | 21/3248 (0.6%) | ||
Back pain | 22/3257 (0.7%) | 26/3248 (0.8%) | ||
Muscle spasms | 79/3257 (2.4%) | 49/3248 (1.5%) | ||
Pain in extremity | 27/3257 (0.8%) | 32/3248 (1%) | ||
Nervous system disorders | ||||
Dizziness | 27/3257 (0.8%) | 17/3248 (0.5%) | ||
Headache | 74/3257 (2.3%) | 92/3248 (2.8%) | ||
Psychiatric disorders | ||||
Anxiety | 16/3257 (0.5%) | 30/3248 (0.9%) | ||
Confusional state | 25/3257 (0.8%) | 28/3248 (0.9%) | ||
Insomnia | 42/3257 (1.3%) | 48/3248 (1.5%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 35/3257 (1.1%) | 34/3248 (1%) | ||
Haematuria | 20/3257 (0.6%) | 20/3248 (0.6%) | ||
Renal failure | 42/3257 (1.3%) | 46/3248 (1.4%) | ||
Renal impairment | 48/3257 (1.5%) | 55/3248 (1.7%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Chronic obstructive pulmonary disease | 6/3257 (0.2%) | 17/3248 (0.5%) | ||
Cough | 41/3257 (1.3%) | 36/3248 (1.1%) | ||
Dyspnoea | 17/3257 (0.5%) | 15/3248 (0.5%) | ||
Epistaxis | 19/3257 (0.6%) | 14/3248 (0.4%) | ||
Vascular disorders | ||||
Hypertension | 23/3257 (0.7%) | 37/3248 (1.1%) | ||
Hypotension | 69/3257 (2.1%) | 58/3248 (1.8%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862-778-8300 |
novartis.email@novartis.com |
- CRLX030A2301
- 2013-001498-25