Trial Outcomes & Findings for Tolvaptan For Worsening Outpatient Heart Failure: Role of Copeptin In Identifying Responders (NCT NCT02476409)
NCT ID: NCT02476409
Last Updated: 2022-05-05
Results Overview
The primary endpoint for the study will be change in body weight between patients randomized to tolvaptan versus placebo from baseline to 48 hours
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
40 participants
Primary outcome timeframe
Baseline, Day 3 (48 hours)
Results posted on
2022-05-05
Participant Flow
Participant milestones
| Measure |
Tolvaptan
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
21
|
|
Overall Study
COMPLETED
|
19
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tolvaptan For Worsening Outpatient Heart Failure: Role of Copeptin In Identifying Responders
Baseline characteristics by cohort
| Measure |
Tolvaptan
n=19 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age, Continuous
|
66 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
60 years
STANDARD_DEVIATION 14 • n=7 Participants
|
63 years
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
39 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
|
Region of Enrollment
United States
|
19 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Left Ventricular Ejection Fraction
|
32 percent ejection fraction (%)
STANDARD_DEVIATION 13 • n=5 Participants
|
34 percent ejection fraction (%)
STANDARD_DEVIATION 18 • n=7 Participants
|
33 percent ejection fraction (%)
STANDARD_DEVIATION 16 • n=5 Participants
|
|
Heart Failure Reduced Ejection Fraction (≤ 40)
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Edema
|
17 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Dyspnea
|
18 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Serum Creatinine
|
1.7 mg/dL
STANDARD_DEVIATION 0.8 • n=5 Participants
|
1.4 mg/dL
STANDARD_DEVIATION 0.6 • n=7 Participants
|
1.6 mg/dL
STANDARD_DEVIATION 0.7 • n=5 Participants
|
|
Serum Sodium
|
140 mEq/L
STANDARD_DEVIATION 3.7 • n=5 Participants
|
138 mEq/L
STANDARD_DEVIATION 3.8 • n=7 Participants
|
139 mEq/L
STANDARD_DEVIATION 3.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 3 (48 hours)Population: One participant in the Tolvaptan group missed study Visit 2 (Day 3 (48 hours)) due to adverse weather. This participant subsequently attended study Visit 3 (Day 8) to complete the study. Thus data were available on 18 of the 19 patients in the Tolvaptan group for this endpoint at study Visit 2 (Day 3 (48 hours)).
The primary endpoint for the study will be change in body weight between patients randomized to tolvaptan versus placebo from baseline to 48 hours
Outcome measures
| Measure |
Tolvaptan
n=18 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Change in Body Weight at 48 Hours
|
-3.3 pounds
Standard Deviation 4.4
|
-0.8 pounds
Standard Deviation 3.5
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3 (48 hours)Population: One participant in the High Copeptin - Tolvaptan group missed study Visit 2 (Day 3 (48 hours)) due to adverse weather. Thus data were available on 11 of the 12 patients in the High Copeptin - Tolvaptan group for this endpoint.
The primary endpoint for the study will be change in body weight between patients randomized to tolvaptan versus placebo from baseline to 48 hours with stratification for baseline copeptin level
Outcome measures
| Measure |
Tolvaptan
n=11 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=12 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
n=7 Participants
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
n=9 Participants
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Change in Body Weight at 48 Hours Stratified by Copeptin
|
-2.9 pounds
Standard Deviation 5.3
|
0.3 pounds
Standard Deviation 3.7
|
-3.8 pounds
Standard Deviation 3.0
|
-2.4 pounds
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: Baseline, Day 3 (48 hours)Population: One participant in the Tolvaptan group missed study Visit 2 (Day 3 (48 hours)) due to adverse weather. This participant subsequently attended study Visit 3 (Day 8) to complete the study. Thus data were available on 18 of the 19 patients in the Tolvaptan group for this endpoint at study Visit 2 (Day 3 (48 hours)).
Changes in patient reported dyspnea scale from baseline to 48 hours based on the visual analog scale. Visual Analog Scale (VAS) - Patient Dyspnea has a minimum value of 0 and a maximum value of 100. Higher scores mean a better outcome.
Outcome measures
| Measure |
Tolvaptan
n=18 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Changes in Visual Analog Scale - Patient Dyspnea
|
21 score on a scale
Standard Deviation 23
|
15 score on a scale
Standard Deviation 22
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 3 (48 hours)Change in loop diuretic dose at 48 hours where doses of loop diuretic are expressed as furosemide milligram equivalents based on standard conversions of bumetanide and torsemide doses to milligram equivalents of furosemide. The formula for the conversion of doses of loop diuretics were standardized to milligram equivalents of furosemide based on 40 milligrams of furosemide for each 1 milligram of bumetanide and 2 milligrams of furosemide for each 1 milligram of torsemide.
Outcome measures
| Measure |
Tolvaptan
n=19 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Change in Loop Diuretic Dose (Furosemide Milligram Equivalents) at 48 Hours
|
-57 furosemide milligram equivalents
Standard Deviation 94
|
-11 furosemide milligram equivalents
Standard Deviation 79
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 3 (48 hours)Number of participants with a decrease in loop diuretic diuretic dosing at 48 hours in the Tolvaptan group and the Placebo group.
Outcome measures
| Measure |
Tolvaptan
n=19 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Number of Participants With a Decrease in Loop Diuretic Dosing at 48 Hours
|
9 Participants
|
4 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 3 (48 hours)Change in loop diuretic score defined by change in loop diuretic use at Visit 2. The change in loop diuretic score endpoint was calculated as follows: patients having an increase in loop diuretic use at Visit 2 were given a score of 2, patients with no change a score of 0, and patients with a decrease in loop use at Visit 2 were given a score of -1. Increases in loop diuretic use were given a higher weighting to account for their reflection of treatment failure.
Outcome measures
| Measure |
Tolvaptan
n=19 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Change in Loop Diuretic Score Defined Based on Change in Loop Diuretic Use
|
-0.47 units on a scale
Standard Deviation 0.51
|
0 units on a scale
Standard Deviation 0.77
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 8 daysChange in body weight at 8 days will be analyzed in a similar fashion to the change in body weight at 48 hours
Outcome measures
| Measure |
Tolvaptan
n=19 Participants
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=20 Participants
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
Low Copeptin - Tolvaptan
Low Copeptin (\< 20 pmol/L) Tolvaptan (augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily)
|
Low Copeptin - Placebo
Low Copeptin (\< 20 pmol/L) Placebo (augmentation of current dose of loop diuretic)
Placebo: Placebo for tolvaptan
|
|---|---|---|---|---|
|
Change in Body Weight at Day 8
|
-1.8 pounds
Standard Deviation 3.5
|
-2.8 pounds
Standard Deviation 4.4
|
—
|
—
|
Adverse Events
Tolvaptan
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tolvaptan
n=19 participants at risk
Augmentation of current dose of loop diuretic + 30 mg of oral tolvaptan daily
Tolvaptan: Study will test the addition of tolvaptan to augmentation of loop diuretic as standard of care for outpatients presenting with worsening heart failure.
|
Placebo
n=21 participants at risk
Augmentation of current dose of loop diuretic
Placebo: Placebo for tolvaptan
|
|---|---|---|
|
Cardiac disorders
Volume Depletion
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
4.8%
1/21 • Number of events 1 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
|
Cardiac disorders
Worsening Heart Failure
|
21.1%
4/19 • Number of events 4 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
14.3%
3/21 • Number of events 3 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Lung Disease
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
0.00%
0/21 • Adverse event data were collected throughout the 30 day study period
Systematic assessment was performed by a combination of methods consisting of standard questionnaires, regular investigator assessment, and regular laboratory testing
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place