ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TT... | NCT02319005

Label	Type	Description	Intervention Names
Revusiran (ALN-TTRSC)	Active Comparator	administered by subcutaneous (SC) injection	Drug: Revusiran (ALN-TTRSC)
Sterile Normal Saline (0.9% NaCl)	Placebo Comparator	administered by subcutaneous (SC) injection	Drug: Sterile Normal Saline (0.9% NaCl)

Name	Type	Description	Arm Group Labels	Other Names
Revusiran (ALN-TTRSC)	Drug		Revusiran (ALN-TTRSC)
Sterile Normal Saline (0.9% NaCl)

Measure	Description	Time Frame
6 Minute Walk Distance (6-MWD)	The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes	18 months
Serum TTR Levels	The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months	18 months

Measure	Description	Time Frame
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization	Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group	18 months
New York Heart Association (NYHA) Class

Name	Affiliation	Role
Jared Gollob, MD	Alnylam Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trial Site		Bakersfield	California		United States
Clinical Trial Site

PubMed Identifier	Type	Citation	Retractions
32062791	Derived	Judge DP, Kristen AV, Grogan M, Maurer MS, Falk RH, Hanna M, Gillmore J, Garg P, Vaishnaw AK, Harrop J, Powell C, Karsten V, Zhang X, Sweetser MT, Vest J, Hawkins PN. Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther. 2020 Jun;34(3):357-370. doi: 10.1007/s10557-019-06919-4.

ID	Title	Description
FG000	Revusiran (ALN-TTRSC)	All patients who received at least 1 dose of revusiran
FG001	Placebo	All patients who received at least 1 dose of placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 19, 2016	Mar 27, 2018

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

6 Minute Walk Distance (6-MWD)

The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes

Study drug was discontinued early due to an imbalance in mortality observed between patients treated with revusiran and placebo. No patients had an 18-month visit, therefore, the endpoints cannot be calculated as data were not collected.

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG0000 OG0010

Primary

Serum TTR Levels

The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization

Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

New York Heart Association (NYHA) Class

The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

Kansas City Cardiomyopathy Questionnaire (KCCQ)

The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

Cardiovascular (CV) Mortality

Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

Cardiovascular (CV) Hospitalization

Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Secondary

All-cause Mortality

Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Posted

18 months

ID	Title	Description
OG000	Revusiran	All patients who received at least 1 dose of revusiran
OG001	Placebo	All patients who received at least 1 dose of placebo

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG00035 events25 affected140 at risk EG00113 events9 affected66 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG00020 events15 affected140 at risk EG00112 events9 affected66 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG00012 events9 affected140 at risk EG0016 events4 affected66 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0008 events7 affected140 at risk EG0013 events2 affected66 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0007 events5 affected140 at risk EG0012 events2 affected66 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0007 events7 affected140 at risk EG0010 events0 affected66 at risk
Syncope	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected140 at risk EG0013 events3 affected66 at risk
Atrial flutter	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0014 events4 affected66 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events3 affected140 at risk EG0013 events3 affected66 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected140 at risk EG0012 events2 affected66 at risk
Hypotension	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events3 affected140 at risk EG0012 events2 affected66 at risk
Renal failure	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events3 affected140 at risk EG0011 events1 affected66 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected140 at risk EG0010 events0 affected66 at risk
Cardiac arrest	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events3 affected140 at risk EG0011 events1 affected66 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0006 events6 affected140 at risk EG0010 events0 affected66 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events2 affected140 at risk EG0011 events1 affected66 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0011 events1 affected66 at risk
Urinary retention	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0012 events2 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0011 events1 affected66 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0012 events2 affected66 at risk
Pneumonia	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0003 events3 affected140 at risk EG0010 events0 affected66 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0011 events1 affected66 at risk
Presyncope	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0014 events2 affected66 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0012 events1 affected66 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Death	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected66 at risk
Subarachnoid hemorrhage	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Sepsis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Asthenia	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected66 at risk
Weight decreased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected66 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Convulsion	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Liver function test abnormal	Investigations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Cardiac amyloidosis	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected66 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected66 at risk
Arrhythmia supraventricular	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Chest pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Urinary tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hypothermia	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Obstructive uropathy	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Haematuria	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Renal impairment	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Hyperglycaemic hyperosmolar nonketotic syndrome	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Nocardiosis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Gastrointestinal amyloidosis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Neuroendocrine tumor	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Mental status changes	Psychiatric disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Epididymitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hepatic enzyme abnormal	Investigations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Heparin-induced thrombocytopenia	Blood and lymphatic system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Cardiorenal syndrome	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Spleen disorders	Blood and lymphatic system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Cutaneous Vasculitis	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Malaise	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Lipoma excision	Surgical and medical procedures	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Infective tenosynovitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Cholangiocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Amnesia	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Gallbladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Metastases to biliary tract	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pneumobilia	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hepatic enzyme increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Systematic inflammatory response syndrome	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Cellulitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Peripheral swelling	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Peripheral artery aneurysm	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Central nervous system lesions	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Atrial Tachycardia	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Drug administration error	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Tachycardia	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Cerebral infarction	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hypertensive crisis	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Diverticulitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Pericardial effusion	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Medical device complication	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Orthostatic hypotensions	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Hepatitis cholestatic	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Gastroenteritis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Low cardiac output syndrome	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Infectious pleural effusion	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Clear cell renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Urosepsis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected66 at risk
Ascites	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Fatigue	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Bronchopneumonia	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Herpes zoster	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Escherichia infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk
Non-cardiac chest pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected66 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection Site Pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG000101 events23 affected140 at risk EG00113 events4 affected66 at risk
Injection site erythema	General disorders	MedDRA (17.1)	Systematic Assessment	EG00064 events16 affected140 at risk EG0010 events0 affected66 at risk
Fatigue	General disorders	MedDRA (17.1)	Systematic Assessment	EG00016 events14 affected140 at risk EG00132 events8 affected66 at risk
Cardiac failure	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG00014 events10 affected140 at risk EG0013 events3 affected66 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG00029 events25 affected140 at risk EG00114 events10 affected66 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG00023 events20 affected140 at risk EG00113 events11 affected66 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG00028 events20 affected140 at risk EG0017 events5 affected66 at risk
Dizziness	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG00019 events18 affected140 at risk EG00115 events13 affected66 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00019 events14 affected140 at risk EG0019 events8 affected66 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG00021 events20 affected140 at risk EG0016 events6 affected66 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG00022 events16 affected140 at risk EG0019 events9 affected66 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG00021 events12 affected140 at risk EG0015 events4 affected66 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG00018 events9 affected140 at risk EG0017 events5 affected66 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG00016 events10 affected140 at risk EG0019 events5 affected66 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG00020 events16 affected140 at risk EG0013 events2 affected66 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG00010 events6 affected140 at risk EG00112 events8 affected66 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG00016 events13 affected140 at risk EG0016 events6 affected66 at risk
Hypotension	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG00015 events11 affected140 at risk EG0014 events4 affected66 at risk
Gout	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0004 events3 affected140 at risk EG00116 events7 affected66 at risk
Asthenia	General disorders	MedDRA (17.1)	Systematic Assessment	EG00018 events15 affected140 at risk EG0012 events2 affected66 at risk
Weight decreased	Investigations	MedDRA (17.1)	Systematic Assessment	EG00014 events12 affected140 at risk EG0015 events4 affected66 at risk
Blood lactic acid increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG00016 events15 affected140 at risk EG0013 events3 affected66 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00010 events9 affected140 at risk EG0018 events6 affected66 at risk
Nasopharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG00011 events11 affected140 at risk EG0015 events5 affected66 at risk
Blood bilirubin increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG00011 events10 affected140 at risk EG0014 events4 affected66 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG00010 events7 affected140 at risk EG0015 events3 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0009 events9 affected140 at risk EG0015 events5 affected66 at risk
Bronchitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG00011 events10 affected140 at risk EG0013 events3 affected66 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00011 events9 affected140 at risk EG0013 events2 affected66 at risk
Liver function test abnormal	Investigations	MedDRA (17.1)	Systematic Assessment	EG00012 events12 affected140 at risk EG0011 events1 affected66 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (17.1)	Systematic Assessment	EG0004 events4 affected140 at risk EG0019 events6 affected66 at risk
Sinusitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0008 events7 affected140 at risk EG0014 events3 affected66 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0008 events8 affected140 at risk EG0014 events4 affected66 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0009 events9 affected140 at risk EG0013 events1 affected66 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0006 events6 affected140 at risk EG0016 events4 affected66 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0009 events9 affected140 at risk EG0012 events2 affected66 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0009 events9 affected140 at risk EG0011 events1 affected66 at risk
Insomnia	Psychiatric disorders	MedDRA (17.1)	Systematic Assessment	EG0008 events8 affected140 at risk EG0012 events2 affected66 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0009 events9 affected140 at risk EG0011 events1 affected66 at risk

ID	Term
D028226	Amyloidosis, Familial
D028227	Amyloid Neuropathies, Familial
D017772	Amyloid Neuropathies
C567782	Amyloidosis, Hereditary, Transthyretin-Related
D009202	Cardiomyopathies
D006333	Heart Failure
D000544	Alzheimer Disease

ID	Term
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D000686	Amyloidosis
D057165	Proteostasis Deficiencies
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D009422	Nervous System Diseases
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D024801	Tauopathies
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Title	Description
BG000	Revusiran	All patients who received at least 1 dose of revusiran
BG001	Placebo	All patients who received at least 1 dose of placebo
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	Revusiran	All patients who received at least 1 dose of revusiran	23	140	83	140	136	140
EG001	Placebo	All patients who received at least 1 dose of placebo	7	66	34	66	62	66