RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01870778
Collaborator
(none)
6,600
542
2
40
12.2
0.3

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

Study Type:
Interventional
Actual Enrollment :
6600 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in Acute Heart Failure Patients
Actual Study Start Date :
Oct 2, 2013
Actual Primary Completion Date :
Jan 23, 2017
Actual Study Completion Date :
Feb 1, 2017

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

  1. 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.

  2. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  • Male or female 18 years of age, with body weight ≤160 kg

  • 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:

  • Persistent dyspnea at rest or with minimal exertion

  • Pulmonary congestion on chest radiograph

  • 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

  • Systolic BP ≥125 mmHg at the start and at the end of screening

  • Able to be randomized within 16 hours from presentation to the hospital, including the emergency department

  • 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:
  • Dyspnea primarily due to non-cardiac causes

  • 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)

  • Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment

  • Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.

  • 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

  • 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

  • Patients with hematocrit <25%, or a history of blood transfusion within the 14 days prior to screening, or active life-threatening GI bleeding.

  • 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.

  • 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

  • Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.

  • 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

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Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01870778
Other Study ID Numbers:
  • CRLX030A2301
  • 2013-001498-25
First Posted:
Jun 6, 2013
Last Update Posted:
Mar 30, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

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

1. Primary Outcome
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
2. Primary Outcome
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
3. Secondary Outcome
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
4. Secondary Outcome
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
5. Secondary Outcome
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
6. Secondary Outcome
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
7. Secondary Outcome
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
8. Secondary Outcome
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
9. Secondary Outcome
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
10. Secondary Outcome
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

[Not Specified]

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
Email novartis.email@novartis.com
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01870778
Other Study ID Numbers:
  • CRLX030A2301
  • 2013-001498-25
First Posted:
Jun 6, 2013
Last Update Posted:
Mar 30, 2018
Last Verified:
Mar 1, 2018