Efficacy, Safety and Tolerability of Sexelaxin When Added... | NCT02007720

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Patients will receive continuous intravenous infusion of matching placebo serelaxin for 48 hours.	Drug: Placebo Other: Standard of CareTherapy
Serelaxin	Experimental	Patients will receive continuous intravenous infusion of serelaxin(30 µg/kg/day) for 48 hours.	Drug: Serelaxin Other: Standard of CareTherapy

Name	Type	Description	Arm Group Labels	Other Names
Serelaxin	Drug	Intravenous infusion	Serelaxin
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change.	The trichotomous clinical composite endpoint of treatment success, treatment failure, or no change. Treatment success defined as improvement of dyspnea by Likert scale and at least 2 points improvement by at least 2 physician assessed signs and symptoms (orthopnea, rales edema, and jugular venous pulse) at Day 2; treatment failure defined as worsening heart failure, death, or re-hospitalization due to heart failure or renal failure through Day 5; no change defined as neither the criteria for treatment success nor the criteria for treatment failure was met through Day 5.	through day 5

Secondary Outcomes

Measure	Description	Time Frame
Time to WHF	Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).	Through Day 5
Time to CV Death	analysis of time to CEC CV death through day 180 : results are given in terms of number of participants with CV death event through day 180 (pre-defined timeframe).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female ≥ 18 years of age, with body weight ≤160 kg
Hospitalized for AHF; AHF is defined as including all of the following measured at any time between presentation (including the emergency department and outpatient clinic) and at the end of screening:
- Persistent dyspnea at rest or with minimal exertion at screening and at the time of randomization
- Pulmonary congestion on chest radiograph
- Brain natriuretic peptide (BNP) ≥500 pg/mL or NT-proBNP ≥2,000 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 and outpatient clinic
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
Renal impairment defined as an estimate glomerular filtration rate using the between presentation and randomization of ≥ 25 and ≤75mL/min/1.73m2, calculated using the Modification of Diet in Renal Disease formula (or modified sMDRD formula according to specific ethnic groups and local practice guidelines).

Exclusion Criteria:

Dyspnea primarily due to non-cardiac causes
Temperature >38.5°C (oral or equivalent), sepsis, active and clinically significant infection requiring IV anti-microbial treatment or known presence or evidence of Human Immunodeficiency Virus (HIV) infection (based on history and/or clinical findings, including laboratory results obtained during screening period).
Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment

*Patients with systolic blood pressure >180 mmHg at the end of screening
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
Hepatic disease unrelated to Heart Failure etiology and as determined by any one of the following: AST and/or ALT values exceeding 3 X ULN and/or bilirubin > 1.5 X ULN at screening or history of hepatic encephalopathy, esophageal varices, or portacaval shunt, or a diagnosis of cirrhosis by any means, or evidence of chronic Hepatitis B (presence of hepatitis B surface antigen production: positive HBsAg), or chronic Hepatitis C infection (presence of Hepatitis C genetic replication: positive Hepatitis C viral RNA, based on history and/or clinical findings, including laboratory results obtained during screening period).

*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 >50 mmHg on prior or current echocardiogram), and severe mitral stenosis
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past year with a life expectancy less than 1 year

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Beijing	Beijing Municipality	100037	China
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
35184572	Derived	Grand J, Miger K, Sajadieh A, Kober L, Torp-Pedersen C, Ertl G, Lopez-Sendon J, Pietro Maggioni A, Teerlink JR, Sato N, Gimpelewicz C, Metra M, Holbro T, Nielsen OW. Blood Pressure Drops During Hospitalization for Acute Heart Failure Treated With Serelaxin: A Patient-Level Analysis of 4 Randomized Controlled Trials. Circ Heart Fail. 2022 Apr;15(4):e009199. doi: 10.1161/CIRCHEARTFAILURE.121.009199. Epub 2022 Feb 21.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
FG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 10, 2016	Mar 5, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Patients With a Clinical Composite Endpoint of Treatment Success, Treatment Failure, or no Change.

The trichotomous clinical composite endpoint of treatment success, treatment failure, or no change. Treatment success defined as improvement of dyspnea by Likert scale and at least 2 points improvement by at least 2 physician assessed signs and symptoms (orthopnea, rales edema, and jugular venous pulse) at Day 2; treatment failure defined as worsening heart failure, death, or re-hospitalization due to heart failure or renal failure through Day 5; no change defined as neither the criteria for treatment success nor the criteria for treatment failure was met through Day 5.

Full analysis set (FAS) - All patients in the randomized population who were not misrandomized patients. Following the intent-to-treat (ITT) principle, patients were analyzed according to the treatment they had been assigned to at the randomization

Posted

Count of Participants

Participants

through day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000433 OG001437

Title

Denominators

Categories

Treatment Failure

Title	Measurements
	OG00036 OG00118

No Change

Title	Measurements
	OG000

Secondary

Time to WHF

Results are given in terms of number of participants with at least one worsening heart failure (WHF) event through day 5 (pre-defined timeframe).

Full analysis set (FAS) - All patients in the randomized population who were not misrandomized patients*. Following the intent-to-treat (ITT) principle, patients were analyzed according to the treatment they had been assigned to at the randomization

Posted

Count of Participants

Participants

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to CV Death

analysis of time to CEC CV death through day 180 : results are given in terms of number of participants with CV death event through day 180 (pre-defined timeframe).

Posted

Count of Participants

Participants

Through Day 180

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to All-cause Death

Results are given in terms of number of participants with all cause death event through day 180 (pre-defined timeframe).

Posted

Count of Participants

Participants

Through Day 180

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to Moderate or Marked Improvements in Dyspnea by Likert Scale, Expressed in Days

Time to event is computed as the number of days from randomization to moderate or marked improvements in dyspnea by Likert scale

Full analysis set (FAS)with measure

Posted

Mean

Standard Deviation

days

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Dyspnea by VAS-AUC Changes

Change from baseline in Dyspena by VAS-AUC through Day 5, expressed in mm-hours

full analysis set with measure

Posted

Mean

Standard Deviation

mm-hours

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization

Length of stay will be defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day

full analysis set with measure

Posted

Mean

Standard Deviation

days

Up to day 30

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Renal Dysfunction and Prevention of Worsening of Renal Function

number of participants with renal dysfunction or in-hospital worsening of renal function through Day 5

Full analysis set with measure

Posted

Number

participants

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to Re-hospitalization Due to Heart Failure and Renal Impairment

Time to event is computed as the number of days from randomization to re-hospitalization due to Heart Failure and renal impairment

Posted

Number

days

Through Day 180

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to CV Death or Re-hospitalization Due to Heart Failure/ Renal Failure

Results are given in terms of number of participants with CV death or at least one re-hospitalization due to Heart Failure through day 180 (pre-defined timeframe).

Posted

Count of Participants

Participants

Through Day 180

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Time to In-hospital Worsening Heart Failure Through Day 5

Results are given in terms of number of participants with at least one in-hospital worsening heart failure through day 5 (pre-defined timeframe). In-hospital worsening heart failure is defined by symptoms only, signs only, and both symptoms and signs.

Full analysis set with measure

Posted

Count of Participants

Participants

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Use of Loop Diuretic and Vasoactive Agents

Number of patients reported with use of loop diuretic and vasoactive agents from randomization through Day 5

full analysis set with measure

Posted

Number

participants

Through Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Cardio-renal Biomarkers

The data was not collected, and analysis not performed, as the trial was terminated prematurely

Posted

Day 2 and Day 5

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Secondary

Number of Patients Reported With Total Adverse Events, Serious Adverse Events and Death.

To evaluate the safety and tolerability of intravenous serelaxin in AHF patients, number of patients with total adverse events, serious adverse events and death will be analyzed.

Posted

Count of Participants

Participants

For the safety evaluation, all adverse events will be collected from signing of the informed consent form through Day 5 for non-serious AEs and through Day 14 for serious AEs.

ID	Title	Description
OG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
OG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Splenic infarction	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Angina pectoris	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Cardiac arrest	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Cardiac failure	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected432 at risk EG0016 affected426 at risk EG0029 affected858 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0012 affected426 at risk EG0023 affected858 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Coronary artery disease	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Myocardial infarction	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Death	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Infusion site thrombosis	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Non-cardiac chest pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0011 affected426 at risk EG0022 affected858 at risk
Sudden cardiac death	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Acinetobacter infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Bronchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 affected432 at risk EG0010 affected426 at risk EG0022 affected858 at risk
Cellulitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Influenza	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Medical device site infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0006 affected432 at risk EG0017 affected426 at risk EG00213 affected858 at risk
Sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Septic shock	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Serratia sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Blood pressure decreased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Hepatic enzyme increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Gout	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0012 affected426 at risk EG0023 affected858 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Cerebral infarction	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected432 at risk EG0011 affected426 at risk EG0023 affected858 at risk
Embolic cerebral infarction	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Encephalopathy	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Partial seizures	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Presyncope	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected432 at risk EG0013 affected426 at risk EG0026 affected858 at risk
Azotaemia	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Polyuria	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Renal impairment	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0013 affected426 at risk EG0023 affected858 at risk
Urinary retention	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0012 affected426 at risk EG0022 affected858 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected432 at risk EG0011 affected426 at risk EG0023 affected858 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected432 at risk EG0011 affected426 at risk EG0023 affected858 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Aortic dissection	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk
Hypotension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0012 affected426 at risk EG0023 affected858 at risk
Hypovolaemic shock	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected432 at risk EG0010 affected426 at risk EG0021 affected858 at risk
Peripheral ischaemia	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected432 at risk EG0011 affected426 at risk EG0021 affected858 at risk

ID	Title	Description
BG000	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.
BG001	Serelaxin	Patients who receivedcontinuous intravenous infusion of serelaxin for 48 hours.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	RLX030	RLX030	34	432	37	432	65	432
EG001	Placebo	Patients who received continuous intravenous infusion of matching placebo serelaxin for 48 hours.	41	426	50	426	82	426
EG002	Total	Total	75	858	87	858	147	858