Comparison of Pre- and Post-discharge Initiation of LCZ69... | NCT02661217

NCT02661217

ID	Type	Description	Link
2015-003266-87	EudraCT Number

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pre-discharge treatment initiation	Other	Patients received first dose at any point after Randomization but no later than 12 h before discharge.	Drug: LCZ696
Post-discharge treatment initiation	Other	Patients received first dose after discharge and up to 14 days thereafter.	Drug: LCZ696

Interventions

Name	Type	Description	Arm Group Labels	Other Names
LCZ696	Drug	LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food. The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization	Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10	10 weeks after Randomization

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid	Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10	10 weeks after Randomization
Percentage of Patients Achieving and Maintaining Any Dose of LCZ696

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Quilmes	Buenos Aires	B1878DKF	Argentina
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37678704	Derived	Straburzynska-Migaj E, Senni M, Wachter R, Fonseca C, Witte KK, Mueller C, Lonn E, Butylin D, Noe A, Schwende H, Lawrence D, Suryawanshi B, Pascual-Figal D; of TRANSITION Investigators. Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study. J Card Fail. 2024 Mar;30(3):425-435. doi: 10.1016/j.cardfail.2023.08.021. Epub 2023 Sep 9.
32800508

Label	URL
Wacther R. et al.: Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.	View source

ID	Title	Description
FG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
FG001	LCZ696 Post-discharge Treatment Initiation

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 18, 2016	Jun 20, 2019

Categories

Title	Measurements
	BG00066.7± 12.27 BG00167.0± 11.67 BG00266.8± 11.97

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000126 BG001125 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Caucasian	BG000488 BG001486 BG002

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 Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization

Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10

Safety Population (SAF). The SAF consisted of all randomized subjects who received at least one dose of study drug with the exception of those patients who were inadvertently randomized into the study. Subjects were analyzed according to treatment actually received.

Posted

Count of Participants

Participants

10 weeks after Randomization

ID	Title	Description
OG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
OG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.

Units	Counts
Participants	OG000493 OG001489

Title

Denominators

Categories

Title	Measurements
	OG000224 OG001248

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.099		Risk Ratio (RR)	0.896			2-Sided	95	0.786	1.021					Superiority

Secondary

Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid

Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10

Posted

Count of Participants

Participants

10 weeks after Randomization

ID	Title	Description
OG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
OG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving and Maintaining Any Dose of LCZ696

Percentage of patients achieving any dose of LCZ696 for at least 2 weeks leading to 10 weeks of treatment

Posted

Count of Participants

Participants

10 weeks after Randomization

ID	Title	Description
OG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
OG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Permanently Discontinued From Treatment

Percentage of patients permanently discontinued from LCZ696 (1) up to week 10 due to AEs, and (2) up to week 26 due to any reasons

Posted

Count of Participants

Participants

10 weeks after Randomization AND 26 weeks after randomization

ID	Title	Description
OG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
OG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.

Units	Counts
Participants	OG000

Post-Hoc

All Collected Deaths

Pre-treatment deaths were collected from randomization until first treatment with LCZ696. The period from randomization to first treatment was up to 14 days.

On-treatment deaths were collected from first treatment with LCZ696 until 26 weeks post randomization.

Safety Population (SAF) and randomized patients who died prior to first dose of study drug. The SAF consisted of all randomized subjects who received at least one dose of study drug with the exception of those patients who were inadvertently randomized into the study. Subjects were analyzed according to treatment actually received.

Posted

Count of Participants

Participants

From randomization until 26 weeks after randomization

ID	Title	Description
OG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
OG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pre-discharge	Pre-discharge	23	493	159	493	200	493
EG001	Post-discharge	Post-discharge	13	489	134	489	201	489
EG002	All Patients	All patients	36	982	293	982	401	982

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0012 affected489 at risk EG0025 affected982 at risk
Hypocoagulable state	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Splenic haemorrhage	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0013 affected489 at risk EG0024 affected982 at risk
Angina pectoris	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0011 affected489 at risk EG0023 affected982 at risk
Angina unstable	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0010 affected489 at risk EG0023 affected982 at risk
Arrhythmia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0011 affected489 at risk EG0023 affected982 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0004 affected493 at risk EG0015 affected489 at risk EG0029 affected982 at risk
Atrial flutter	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Atrial tachycardia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0012 affected489 at risk EG0024 affected982 at risk
Bradycardia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0011 affected489 at risk EG0023 affected982 at risk
Cardiac arrest	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0004 affected493 at risk EG0011 affected489 at risk EG0025 affected982 at risk
Cardiac failure	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG00046 affected493 at risk EG00145 affected489 at risk EG00291 affected982 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG00011 affected493 at risk EG0019 affected489 at risk EG00220 affected982 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0012 affected489 at risk EG0025 affected982 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0014 affected489 at risk EG0025 affected982 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0015 affected489 at risk EG0026 affected982 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0012 affected489 at risk EG0022 affected982 at risk
Coronary artery disease	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Left ventricular failure	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Low cardiac output syndrome	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Myocardial fibrosis	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Myocardial infarction	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Palpitations	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Sinus arrest	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0012 affected489 at risk EG0025 affected982 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Hypothyroidism	Endocrine disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0013 affected489 at risk EG0023 affected982 at risk
Diarrhoea haemorrhagic	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Gastritis	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Lip swelling	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Melaena	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Subileus	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Asthenia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Impaired healing	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Non-cardiac chest pain	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0015 affected489 at risk EG0027 affected982 at risk
Oedema peripheral	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0013 affected489 at risk EG0024 affected982 at risk
Pyrexia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Sudden cardiac death	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Sudden death	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Hepatitis	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Bacterial sepsis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Biliary sepsis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Bronchitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0014 affected489 at risk EG0025 affected982 at risk
Catheter site abscess	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Cellulitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Device related infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Diarrhoea infectious	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Endocarditis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Epididymitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Erysipelas	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0013 affected489 at risk EG0024 affected982 at risk
Gangrene	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Gastroenteritis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0013 affected489 at risk EG0024 affected982 at risk
Influenza	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Localised infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Lung infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Pneumonia	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0007 affected493 at risk EG0018 affected489 at risk EG00215 affected982 at risk
Postoperative wound infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Q fever	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0014 affected489 at risk EG0024 affected982 at risk
Sepsis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0011 affected489 at risk EG0023 affected982 at risk
Septic phlebitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Septic shock	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Tuberculosis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Urinary tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0004 affected493 at risk EG0012 affected489 at risk EG0026 affected982 at risk
Urosepsis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Multiple injuries	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Transplant failure	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Blood creatinine increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Cardiac output decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Ejection fraction abnormal	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Ejection fraction decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0012 affected489 at risk EG0022 affected982 at risk
General physical condition abnormal	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Heart rate abnormal	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Hepatic enzyme abnormal	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Hepatic enzyme increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
International normalised ratio increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Weight increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Gout	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0016 affected489 at risk EG0029 affected982 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Malignant neoplasm of ampulla of Vater	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Malignant peritoneal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Aphasia	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Autonomic nervous system imbalance	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Brain injury	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Cerebral arteriosclerosis	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Cognitive disorder	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Dizziness	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Extrapyramidal disorder	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Headache	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Hypoxic-ischaemic encephalopathy	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0012 affected489 at risk EG0022 affected982 at risk
Loss of consciousness	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Presyncope	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Sciatica	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Syncope	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0013 affected489 at risk EG0026 affected982 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Device battery issue	Product Issues	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Device dislocation	Product Issues	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Insomnia	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG00012 affected493 at risk EG0017 affected489 at risk EG00219 affected982 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0012 affected489 at risk EG0025 affected982 at risk
Haematuria	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0012 affected489 at risk EG0022 affected982 at risk
Renal failure	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0014 affected489 at risk EG0027 affected982 at risk
Renal impairment	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0014 affected489 at risk EG0024 affected982 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0014 affected489 at risk EG0027 affected982 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0011 affected489 at risk EG0022 affected982 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0006 affected493 at risk EG0015 affected489 at risk EG00211 affected982 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Mediastinal haematoma	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Orthopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0003 affected493 at risk EG0017 affected489 at risk EG00210 affected982 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0012 affected489 at risk EG0023 affected982 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Aortic aneurysm	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected493 at risk EG0011 affected489 at risk EG0021 affected982 at risk
Hypertension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Hypotension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0006 affected493 at risk EG0012 affected489 at risk EG0028 affected982 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected493 at risk EG0010 affected489 at risk EG0021 affected982 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected493 at risk EG0010 affected489 at risk EG0022 affected982 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG00017 affected493 at risk EG00129 affected489 at risk EG00246 affected982 at risk
Oedema peripheral	General disorders	MedDRA (21.0)	Systematic Assessment	EG00020 affected493 at risk EG00126 affected489 at risk EG00246 affected982 at risk
Urinary tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG00029 affected493 at risk EG00119 affected489 at risk EG00248 affected982 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG00067 affected493 at risk EG00159 affected489 at risk EG002126 affected982 at risk
Dizziness	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG00032 affected493 at risk EG00130 affected489 at risk EG00262 affected982 at risk
Renal impairment	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG00036 affected493 at risk EG00124 affected489 at risk EG00260 affected982 at risk
Hypotension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG00071 affected493 at risk EG00167 affected489 at risk EG002138 affected982 at risk

ID	Title	Description
BG000	LCZ696 Pre-discharge Treatment Initiation	Patients received first dose at any point after Randomization but no later than 12 h before discharge.
BG001	LCZ696 Post-discharge Treatment Initiation	Patients received first dose after discharge and up to 14 days thereafter.
BG002	Total	Total of all reporting groups