Trial Outcomes & Findings for Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (NCT NCT02228408)
NCT ID: NCT02228408
Last Updated: 2021-04-27
Results Overview
Rate of primary Safety Outcomes(hypotension, serious adverse events, GI events and CV death)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
17 participants
Primary outcome timeframe
6 months
Results posted on
2021-04-27
Participant Flow
Participant milestones
| Measure |
Hydralazine/Isorsorbide Dinitrate
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
10
|
|
Overall Study
COMPLETED
|
7
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD
Baseline characteristics by cohort
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
63 years
n=7 Participants
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 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
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 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
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
10 participants
n=7 Participants
|
17 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: intent to treat
Rate of primary Safety Outcomes(hypotension, serious adverse events, GI events and CV death)
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
intradialytic hpypotension
|
1 Participants
|
6 Participants
|
|
Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
SAE
|
5 Participants
|
3 Participants
|
|
Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
Nausea
|
4 Participants
|
3 Participants
|
|
Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
CV death rate per patient year
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 0 to 6 monthsPopulation: intent to treat
Primary Efficacy Measure-CFR measured on rest and stress Positron Emission Tomography
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=6 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months
|
-0.27 ratio
Standard Deviation 0.23
|
-0.03 ratio
Standard Deviation 0.46
|
PRIMARY outcome
Timeframe: 0 to 6 monthsPopulation: intent to treat
Co-primary efficacy measure measured on Tissue Doppler Echocardiography
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=6 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Change in E' on TDI Echo From 0-6 Months
|
0.56 cm/s
Standard Deviation 1.1
|
-0.04 cm/s
Standard Deviation 0.92
|
PRIMARY outcome
Timeframe: 0 to 6 monthsPopulation: intent to treat
Primary Tolerability measure
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Reduction in Drug Dose or Discontinuation of Study Drug
discontinuation
|
0 Participants
|
0 Participants
|
|
Reduction in Drug Dose or Discontinuation of Study Drug
reduction
|
2 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: 0 to 6 monthsPrimary Feasibility Measure
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Number of Patients Completing Study From 0 to 6 Months
|
6 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 0 to 6 monthsPopulation: Not done-data. samples not analyzed due to lack of additional funding.
Circulating concentrations of markers such as the carboxy terminal of pro-collagen type 1 or ADMA will be measured
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 0 to 6 monthsChange in left ventricular mass index between baseline and 6 months.
Outcome measures
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=6 Participants
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 Participants
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Change in LVMI
|
-10.6 g/m2
Standard Deviation 8.5
|
-8 g/m2
Standard Deviation 11.1
|
Adverse Events
Hydralazine/Isorsorbide Dinitrate
Serious events: 5 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 participants at risk
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 participants at risk
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Gastrointestinal disorders
nausea
|
14.3%
1/7 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Gastrointestinal disorders
vomitting
|
14.3%
1/7 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Cardiac disorders
cv hospitalization
|
14.3%
1/7 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Injury, poisoning and procedural complications
fall
|
14.3%
1/7 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Blood and lymphatic system disorders
av fisula thrombosis
|
0.00%
0/7 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Gastrointestinal disorders
gi bleeding
|
14.3%
1/7 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
Other adverse events
| Measure |
Hydralazine/Isorsorbide Dinitrate
n=7 participants at risk
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Hydralazine/Isorsorbide Dinitrate: Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
|
Placebo
n=10 participants at risk
Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Placebo: Placebo titration will mimic titration of active study arm
|
|---|---|---|
|
Gastrointestinal disorders
diarrhea
|
28.6%
2/7 • Number of events 2 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Gastrointestinal disorders
headache
|
71.4%
5/7 • Number of events 8 • 6 months
|
70.0%
7/10 • Number of events 7 • 6 months
|
|
Gastrointestinal disorders
vomitting
|
14.3%
1/7 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place