Phase IIb Safety and Efficacy Study of Four Dose Regimens... | NCT01951638

NCT01951638

ID	Type	Description	Link
2013-002288-25	EudraCT Number

Status Module

Oversight Module

Description 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
Vericiguat (BAY1021189)(10 mg)	Experimental	2.5 mg orally once daily for 2 weeks, up-titration to 5 mg orally once daily for 2 weeks, up-titration to 10 mg orally once daily for 8 weeks	Drug: Vericiguat (BAY1021189) (1.25 mg) Drug: Vericiguat (BAY1021189) (5 mg)
Vericiguat (BAY1021189) (5 mg)	Experimental	2.5 mg orally once daily for 2 weeks, then 5 mg orally once daily for 10 weeks (with sham titration)	Drug: Vericiguat (BAY1021189) (1.25 mg) Drug: Vericiguat (BAY1021189) (5 mg)
Vericiguat (BAY1021189) (2.5 mg)	Experimental	2.5 mg orally once daily for 12 weeks (with sham titrations)	Drug: Vericiguat (BAY1021189) (1.25 mg)
Vericiguat (BAY1021189) (1.25 mg)	Experimental	1.25 mg orally once daily for 12 weeks (with sham titrations)	Drug: Vericiguat (BAY1021189) (1.25 mg)
Placebo	Placebo Comparator	Orally once daily for 12 weeks (with sham titrations)	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Vericiguat (BAY1021189) (1.25 mg)	Drug	1.25 mg BAY1021189 tablets	Vericiguat (BAY1021189) (1.25 mg) Vericiguat (BAY1021189) (2.5 mg) Vericiguat (BAY1021189) (5 mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in Log-transformed N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)	NTproBNP is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure (HF).	Baseline, Week 12 (end of treatment [EOT])
Change From Baseline to Week 12 in Left Atrial Volume (LAV)	Left atrial volume was measured by echocardiography.	Baseline, Week 12 (EOT)

Other Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Blood pressure was measured after at least 10 minutes resting in a sitting position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.	Baseline, Week 12 (EOT)

Eligibility Module

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Fountain Valley	California	92708	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25056511	Background	Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Muller K, Roessig L, Gheorghiade M; SOCRATES Investigators and Coordinators. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026-38. doi: 10.1002/ejhf.135. Epub 2014 Jul 24.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
FG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
BG001	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
BG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
BG003	BAY1021189 2.5 mg to 5 mg	Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.
BG004	BAY1021189 2.5 mg to 10 mg	Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-0.098± 0.778 OG001-0.047± 0.788 OG0020.071± 0.818 OG003

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	For the primary analysis, the three highest active treatment groups BAY1021189 (2.5mg, 2.5 to 5mg, 2.5 to 10mg) were pooled and compared to the assigned placebo treatment group with a one-sided two-sample t-test. The Hochberg procedure was used to test the two primary end points at study-wise significance level of 5%. Results are reported including 90% confidence intervals (CI) for the difference of means. The difference between the comparison groups is difference of means on the log scale.	t-test, 1 sided		= 0.8991		Log-Scale mean difference	0.137			2-Sided	90	-0.04	0.31					Other

Primary

Change From Baseline to Week 12 in Left Atrial Volume (LAV)

Left atrial volume was measured by echocardiography.

PPS Left Atrial Volume (LAV) included all subjects randomized to treatment who had a valid measurement of LAV at baseline and at Week 12 (Visit 5) and showed no major protocol deviations.

Posted

Mean

Standard Deviation

milliliter

Baseline, Week 12 (EOT)

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG003	BAY1021189 2.5 mg to 5 mg	Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg after 14 or 28 days. Sham titration included on Day 28.

Other Pre-specified

Change From Baseline to Week 12 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressure was measured after at least 10 minutes resting in a sitting position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.

Safety Analysis Set (SAF) with evaluable subjects for this endpoint.

Posted

Mean

Standard Deviation

millimeter of mercury

Baseline, Week 12 (EOT)

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG003	BAY1021189 2.5 mg to 5 mg

Other Pre-specified

Change From Baseline to Week 12 in Heart Rate

Heart rate was measured after 10 minutes resting in a sitting position (3 measurements taken approximatly 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.

Safety Analysis Set (SAF) with evaluable subjects for this endpoint.

Posted

Mean

Standard Deviation

beats per minute

Baseline, Week 12 (EOT)

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG003	BAY1021189 2.5 mg to 5 mg

Other Pre-specified

Number of Subjects With Clinical Events (Heart Failure Hospitalization and Cardio-vascular [CV] Mortality)

Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.

Full Analysis Set (FAS) included all subjects who were randomized to treatment.

Posted

Count of Participants

Participants

Baseline up to Week 16 including 12 week treatment period and 4 week follow-up period

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.
OG003	BAY1021189 2.5 mg to 5 mg

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	Placebo	Subjects received placebo matched to vericiguat (BAY1021189) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	1	93	20	93	21	93
EG001	BAY1021189 1.25 mg	Subjects received vericiguat (Verquvo, BAY1021189) 1.25 milligram (mg) orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	0	96	20	96	33	96
EG002	BAY1021189 2.5 mg	Subjects received vericiguat (Verquvo, BAY1021189) 2.5 mg orally once daily for 12 weeks. Sham titrations included on Days 14 and 28.	1	95	24	95	40	95
EG003	BAY1021189 From 2.5 to 5 mg	Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 or 28 days. Sham titration included on Day 28.	7	95	18	95	38	95
EG004	BAY1021189 From 2.5 to 10 mg	Subjects received vericiguat (Verquvo, BAY1021189) for 12 weeks, starting on 2.5 mg once daily with potential up-titration to 5 mg once daily after 14 days, and up-titration to 10 mg once daily after 28 days.	2	96	21	96	33	96

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events2 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG0030 events0 affected95 at risk EG0041 events1 affected96 at risk
Anaemia of chronic disease	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0023 events2 affected95 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0006 events6 affected93 at risk EG0014 events4 affected96 at risk EG00212 events7 affected95 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0023 events3 affected95 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events2 affected93 at risk EG0014 events4 affected96 at risk EG0023 events3 affected95 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Cardiogenic shock	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Right ventricular failure	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Tachyarrhythmia	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0012 events2 affected96 at risk EG0020 events0 affected95 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Vitreous haemorrhage	Eye disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Chest pain	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Pain	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Pyrexia	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Sudden death	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Carbuncle	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Diabetic gangrene	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Erysipelas	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Gangrene	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Hepatitis C	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0002 events1 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Respiratory syncytial virus bronchiolitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Urosepsis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Enterococcal sepsis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Chlamydial infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Coagulation time prolonged	Investigations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Intraocular pressure increased	Investigations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Gastrointestinal stromal tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Presyncope	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Cervicogenic headache	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected93 at risk EG0011 events1 affected96 at risk EG0021 events1 affected95 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0021 events1 affected95 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0021 events1 affected95 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Eyelid operation	Surgical and medical procedures	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Circulatory collapse	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected96 at risk EG0020 events0 affected95 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events5 affected93 at risk EG0011 events1 affected96 at risk EG0024 events3 affected95 at risk EG0033 events3 affected95 at risk EG0042 events2 affected96 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0025 events5 affected95 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected93 at risk EG0012 events2 affected96 at risk EG0025 events4 affected95 at risk EG003
Fatigue	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events2 affected93 at risk EG0012 events2 affected96 at risk EG0023 events3 affected95 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events2 affected93 at risk EG0014 events3 affected96 at risk EG0023 events2 affected95 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0022 events2 affected95 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected93 at risk EG0014 events4 affected96 at risk EG0028 events6 affected95 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected93 at risk EG0016 events6 affected96 at risk EG0022 events2 affected95 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected93 at risk EG0014 events2 affected96 at risk EG00211 events10 affected95 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0026 events6 affected95 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events2 affected93 at risk EG0015 events5 affected96 at risk EG0020 events0 affected95 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected96 at risk EG0020 events0 affected95 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0015 events5 affected96 at risk EG0026 events6 affected95 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected93 at risk EG0017 events6 affected96 at risk EG00210 events9 affected95 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected93 at risk EG0014 events4 affected96 at risk EG0026 events4 affected95 at risk EG003

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases