Phase 4
N=17
Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD
Chronic Hemodialysis (ESRD)
Bottom Line
View on ClinicalTrials.gov: NCT02228408 ↗Enrolled (actual)
17
Serious AEs
47.1%
Results posted
Apr 2021
Primary outcome: Primary: Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death — 1; 6; 5; 3 Participants — p=0.04
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Hydralazine/Isorsorbide Dinitrate (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Brigham and Women's Hospital
- Primary completion
- May 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death |
1; 6; 5; 3; 4; 3 | 0.04 sig |
| PRIMARY Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months |
-0.27; -0.03 | 0.19 |
| PRIMARY Change in E' on TDI Echo From 0-6 Months |
0.56; -0.04 | 0.34 |
| PRIMARY Reduction in Drug Dose or Discontinuation of Study Drug |
0; 0; 2; 3 | — |
| PRIMARY Number of Patients Completing Study From 0 to 6 Months |
6; 10 | — |
| SECONDARY Change in Circulating Fibrosis Markers and Angiogenesis Markers |
— | — |
| SECONDARY Change in LVMI |
-10.6; -8 | 0.62 |
Summary
This study is a pilot study designed to compare the safety and cardiovascular effects of 26 weeks of combination hydralazine/isorsorbide dinitrate therapy with placebo therapy in patients receiving chronic hemodialysis.
The investigators hypothesize that treatment of chronic hemodialysis (ESRD) patients with a combination of hydralazine/isosorbide dinitrate compared with placebo is safe and that it will improve heart function as well blood flow/blood vessel supply.
Eligibility Criteria
Inclusion Criteria
- Maintenance hemodialysis therapy for end-stage renal disease
- Age 18-85 years
- ≥ 90 days since dialysis initiation
- Ability to provide informed consent
- Pre-dialysis seated systolic blood pressure measurements must be ≥ 120 mm Hg in the 2 weeks before enrollment and on the day of randomization.
Exclusion Criteria
- Serum potassium ≥6.5 mEq/L within 2 months prior to screening
- Unscheduled dialysis for hyperkalemia within the 3 months prior to screening
- Hypotension defined as pre-dialysis SBP <100 mm Hg (seated measurement) within 4 weeks prior to enrollment
- Recurrent intra-dialytic hypotension, defined as systolic blood pressure <80 mm Hg during ≥3 dialysis sessions per 30-day rolling period or treatment for either hypotension or symptoms of hypotension if systolic blood pressure is < 100 mm Hg during ≥3 dialysis sessions per 30-day rolling period.
- Mitral valve repair or replacement
- Severe mitral valve disease by echocardiography, coronary angiography or cardiac magnetic resonance imaging
- Prior coronary artery bypass graft
- Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another dialysis unit within 6 months
- Expected survival < 6 months
- Allergy to study medications (ISD, HY, adenosine/diprimidole)
- Active use of sildenafil, vardenafil or tadalafil
- History of severe aortic stenosis or other cause of LV outflow obstruction
- Pregnancy, anticipated pregnancy, or breastfeeding, confirmed by serum pregnancy test on the day of PET scan
- Incarceration
- Participation in another intervention study
- Use of monoamine oxidase inhibitors
- Contraindication to adenosine including
- 2nd or 3rd degree heart block, sick sinus syndrome or symptomatic bradycardia (without a functioning pacemaker)
- moderate or severe asthma
- chronic obstructive pulmonary disease
- Active use of any of the study medications unless participant and physician willing to discontinue prior to enrollment.
Data sourced from ClinicalTrials.gov (NCT02228408). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.