Trial Outcomes & Findings for Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure (NCT NCT02235077)

NCT ID: NCT02235077

Last Updated: 2017-06-14

Results Overview

The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 360 participants
• Primary outcome timeframe: Randomization to 96 hours
• Results posted on: 2017-06-14

Participant Flow

Participant milestones

Measure	Spironolactone Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Overall Study STARTED	182	178
Overall Study COMPLETED	164	159
Overall Study NOT COMPLETED	18	19

Reasons for withdrawal

Measure	Spironolactone Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Overall Study Death	5	7
Overall Study Lost to Follow-up	5	6
Overall Study Withdrawal by Subject	8	5
Overall Study Physician Decision	0	1

Baseline Characteristics

Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure

Baseline characteristics by cohort

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Total n=360 Participants Total of all reporting groups
Age, Continuous	65.9 years STANDARD_DEVIATION 13.7 • n=5 Participants	63.5 years STANDARD_DEVIATION 14.4 • n=7 Participants	64.7 years STANDARD_DEVIATION 14.1 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	64 Participants n=7 Participants	129 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	114 Participants n=7 Participants	231 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	180 Participants n=5 Participants	172 Participants n=7 Participants	352 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	74 Participants n=5 Participants	77 Participants n=7 Participants	151 Participants n=5 Participants
Race (NIH/OMB) White	101 Participants n=5 Participants	99 Participants n=7 Participants	200 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to 96 hours

The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.

Outcome measures

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in NT-proBNP	-0.58 log pg/ml Standard Deviation 0.69	-0.61 log pg/ml Standard Deviation 0.72

SECONDARY outcome

Timeframe: Randomization through 96 hours

Clinical congestion score will be assessed at randomization, 96 hours, and at discharge. Scale consisted of sum of six signs and symptoms of congestion, each scored 0-3. Zero indicates no sign/symptom and 3 indicates worst case of sign/symptom. Score range 0-18 with 18 being worst score.

Outcome measures

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Clinical Congestion Score	-5.59 units on a scale Standard Deviation 3.34	-5.82 units on a scale Standard Deviation 3.32

SECONDARY outcome

Timeframe: Randomization through 96 hours

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Dyspnea relief via 7-point Likert scale will be assessed at randomization, 96 hours, and at discharge. The Likert score was defined as 1=markedly improved, 2=moderately improved, 3=minimally improved; 4=no change, 5=minimally worse, 6=moderately worse, and 7=markedly worse as compared with the degree of dyspnea present at randomization.

Outcome measures

Measure	Spironolactone n=166 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=163 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Dyspnea Likert Score No change	17 Participants	21 Participants
96 Hour Change in Dyspnea Likert Score Markedly improved	64 Participants	79 Participants
96 Hour Change in Dyspnea Likert Score Moderately improved	56 Participants	39 Participants
96 Hour Change in Dyspnea Likert Score Minimally improved	24 Participants	18 Participants
96 Hour Change in Dyspnea Likert Score Minimally worse	4 Participants	5 Participants
96 Hour Change in Dyspnea Likert Score Moderately worse	0 Participants	0 Participants
96 Hour Change in Dyspnea Likert Score Markedly worse	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Randomization through 96 hours

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Renal function via serum creatinine, will be assessed at randomization and daily through 96 hours

Outcome measures

Measure	Spironolactone n=100 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=101 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Serum Creatinine	0.15 mg/dl Standard Deviation 0.30	0.16 mg/dl Standard Deviation 0.30

SECONDARY outcome

Timeframe: Randomization through 96 hours

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Fluid intake and urine output will be assessed daily while in hospital through 96 hours. Net fluid output (output minus input) through 96 hours is reported.

Outcome measures

Measure	Spironolactone n=87 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=96 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Net Fluid Output	5824 ml Standard Deviation 4007	5507 ml Standard Deviation 3633

SECONDARY outcome

Timeframe: Randomization through 96 hours or earlier discharge

Baseline body weight assessment will be completed, and changes in weight documented daily through 96 hours or earlier discharge

Outcome measures

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Body Weight	-8.1 pounds Standard Deviation 10.7	-7.5 pounds Standard Deviation 9.5

SECONDARY outcome

Timeframe: Baseline, 96 hours

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Change in serum potassium levels at 96 hours as compared to baseline.

Outcome measures

Measure	Spironolactone n=99 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=101 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Serum Potassium Levels	0.31 mEq/L Standard Deviation 0.54	0.15 mEq/L Standard Deviation 0.69

SECONDARY outcome

Timeframe: Randomization through Day 30

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Medications will be reviewed to assess loop diuretic dose requirements through Day 30 following randomization

Outcome measures

Measure	Spironolactone n=164 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=158 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Change in Loop Diuretics Requirements From Baseline to 30 Days	19.66 mg Standard Deviation 69.95	30.70 mg Standard Deviation 68.29

SECONDARY outcome

Timeframe: Hospital discharge through Day 30

Population: All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Outpatient worsening heart failure symptoms will be assessed from discharge through Day 30

Outcome measures

Measure	Spironolactone n=166 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=163 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30	19 Participants	17 Participants

SECONDARY outcome

Timeframe: Randomization to 96 hours

Dyspnea visual analog scale change from randomization to 96 hours. Scale range 0-100 with 100 being the best possible score.

Outcome measures

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
96 Hour Change in Dyspnea Visual Analog Scale	17.2 units on a scale Standard Deviation 25.0	17.9 units on a scale Standard Deviation 24.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 60 days post randomization

All participants will be contacted by telephone at 60 days, +/- 3 days post randomization to assess vital status (death).

Outcome measures

Measure	Spironolactone n=182 Participants Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 Participants Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Day 60 Mortality	8 Participants	10 Participants

Adverse Events

Spironolactone

Serious events: 21 serious events

Other events: 0 other events

Deaths: 5 deaths

Placebo

Serious events: 13 serious events

Other events: 0 other events

Deaths: 7 deaths

Serious adverse events

Measure	Spironolactone n=182 participants at risk Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	Placebo n=178 participants at risk Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
Blood and lymphatic system disorders Anaemia	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Cardiac disorders Aortic valve stenosis	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Cardiac disorders Cardiogenic shock	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Gastrointestinal disorders Gastrointestinal Haemmorhage	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Gastrointestinal disorders Protalgia	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
General disorders Multi-organ failure	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
General disorders Non-cardiac chest pain	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
General disorders Systemic inflammatory response syndrome	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Infections and infestations H1N1 Influenza	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Infections and infestations Oesophageal Candidiasis	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Infections and infestations Pneumonia	1.6% 3/182 • Number of events 3 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Infections and infestations Tooth abscess	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Infections and infestations Urinary tract infection	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Injury, poisoning and procedural complications Fall	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Injury, poisoning and procedural complications Post-procedural haemotoma	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Injury, poisoning and procedural complications Traumatic haemotoma	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Investigations International Normalised Ratio Increased	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Metabolism and nutrition disorders Gout	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Metabolism and nutrition disorders Hyperglycaemia	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Metabolism and nutrition disorders Hypokalaemia	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Metabolism and nutrition disorders Lactic acidosis	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Nervous system disorders Hepatic encephalopathy	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Nervous system disorders Partial seizures with secondary generalisation	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Psychiatric disorders Delerium	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Psychiatric disorders Psychogenic seizure	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Psychiatric disorders Suicidal ideation	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 4/182 • Number of events 4 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Respiratory, thoracic and mediastinal disorders Bronchial haemmorhage	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Aortic dissection	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Distributive shock	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Hypertension	0.00% 0/182 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.56% 1/178 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Hypertensive crisis	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Hypertensive emergency	1.1% 2/182 • Number of events 2 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Hypotension	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Vascular disorders Hypovolaemic shock	0.55% 1/182 • Number of events 1 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.	0.00% 0/178 • Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms. Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.

Other adverse events

Adverse event data not reported

Additional Information

Adrian Hernandez, MD

Duke Clinical Research Institute

Phone: 919 668 7515

Email: adrian.hernandez@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee To minimize the probability of inaccurate data in published materials, it is the policy of the Heart Failure Network that all data and text considered for all papers, and all abstracts for presentation at scientific meetings be submitted to the Publication and Presentation Subcommittee, the NHLBI Project Officer, and the Coordinating Center for review and approval prior to presentation or publication.
• Publication restrictions are in place

Restriction type: OTHER