Trial Outcomes & Findings for Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure (NCT NCT01544998)
NCT ID: NCT01544998
Last Updated: 2018-03-22
Results Overview
Value at 60 minutes minus value at baseline.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Baseline, 60 minutes after saline load
Results posted on
2018-03-22
Participant Flow
Participants were recruited at the Mayo Clinic in Rochester, Minnesota.
2 participants in the Preclinical Systolic Dysfunction group withdrew from the study before they were randomized. No participant in the Preclinical Diastolic Dysfunction group withdrew.
Participant milestones
| Measure |
Tadalafil Plus Placebo, Then Tadalafil Plus Nesiritide
First intervention period: oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. There was a one week washout period. Second intervention period: oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting.
|
Tadalafil Plus Nesiritide, Then Tadalafil Plus Placebo
First intervention period: oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. There was a one week washout period. Second intervention period: oral Tadalafil; after 1 hour, sc placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting.
|
|---|---|---|
|
First Intervention (3 Hours)
STARTED
|
26
|
15
|
|
First Intervention (3 Hours)
COMPLETED
|
26
|
15
|
|
First Intervention (3 Hours)
NOT COMPLETED
|
0
|
0
|
|
Washout (1 Week)
STARTED
|
26
|
15
|
|
Washout (1 Week)
COMPLETED
|
26
|
15
|
|
Washout (1 Week)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (3 Hours)
STARTED
|
26
|
15
|
|
Second Intervention (3 Hours)
COMPLETED
|
26
|
15
|
|
Second Intervention (3 Hours)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=41 Participants
Includes groups randomized to receive Tadalafil plus Nesiritide first, and Tadalafil plus Placebo first.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
25 Participants
n=5 Participants
|
|
Age, Continuous
|
69.3 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PSD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=21 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=21 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes for Preclinical Systolic Dysfunction (PSD) Reporting Group
|
41.8 mEq/min
Standard Deviation 161.8
|
88.9 mEq/min
Standard Deviation 86.5
|
PRIMARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PDD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=20 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=20 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes for Preclinical Diastolic Dysfunction (PDD) Reporting Group
|
92.5 mEq/min
Standard Deviation 185
|
97.0 mEq/min
Standard Deviation 183
|
SECONDARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PSD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=21 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=21 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Glomerular Filtration Rate (GFR) at 60 Minutes for Preclinical Systolic Dysfunction (PSD) Reporting Group
|
-12.7 mL/min/1.73 m^2
Standard Deviation 21.2
|
9.4 mL/min/1.73 m^2
Standard Deviation 22.7
|
SECONDARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PDD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=20 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=20 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Glomerular Filtration Rate (GFR) at 60 Minutes for Preclinical Diastolic Dysfunction (PDD) Reporting Group
|
-5.3 mL/min/1.73 m^2
Standard Deviation 26.1
|
3.9 mL/min/1.73 m^2
Standard Deviation 24.3
|
SECONDARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PSD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=20 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=20 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes for Preclinical Systolic Dysfunction (PSD) Reporting Group
|
2566.9 pmol/min
Standard Deviation 1888.3
|
34.2 pmol/min
Standard Deviation 354.9
|
SECONDARY outcome
Timeframe: Baseline, 60 minutes after saline loadPopulation: This was a within PSD reporting group comparison; between PSD and PDD groups were not compared.
Value at 60 minutes minus value at baseline.
Outcome measures
| Measure |
Tadalafil Plus Nesiritide
n=20 Participants
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
Tadalafil Plus Placebo
n=20 Participants
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|
|
Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes for Preclinical Diastolic Dysfunction (PDD) Reporting Group
|
1851 pmol/min
Standard Deviation 1386.4
|
173.4 pmol/min
Standard Deviation 517.9
|
Adverse Events
PSD: Tadalafil Plus Nesiritide
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
PSD: Tadalafil Plus Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
PDD: Tadalafil Plus Nesiritide
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
PDD: Tadalafil Plus Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PSD: Tadalafil Plus Nesiritide
n=21 participants at risk
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
PSD: Tadalafil Plus Placebo
n=21 participants at risk
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
PDD: Tadalafil Plus Nesiritide
n=20 participants at risk
Oral Tadalafil; after 1 hour, sc Nesiritide given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
PDD: Tadalafil Plus Placebo
n=20 participants at risk
Oral Tadalafil; after 1 hour, subcutaneous (sc) placebo given in the abdomen. After a lead in period of 15 min, a 30-min clearance was repeated, then acute saline load was given. During the 1 hour saline load, one 30-min clearance repeated with subject in supine position, then second 30-min clearance repeated with subject sitting. This dosing administration was in either first intervention period or second intervention period.
|
|---|---|---|---|---|
|
Cardiac disorders
Hypotension
|
4.8%
1/21 • Number of events 1 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
10.0%
2/20 • Number of events 2 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
|
General disorders
Chest Discomfort
|
4.8%
1/21 • Number of events 1 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
9.5%
2/21 • Number of events 2 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
5.0%
1/20 • Number of events 1 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
|
Skin and subcutaneous tissue disorders
IV Site Redness
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/21 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
5.0%
1/20 • Number of events 1 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
0.00%
0/20 • Adverse events were collected from randomization through 7 days after the completion of the second study day.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place