Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD

Condition(s) targeted: Chronic Hemodialysis (ESRD)

Intervention: Hydralazine/Isorsorbide Dinitrate (Drug); Amlodipine and Placebo (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Brigham and Women's Hospital

Official(s) and/or principal investigator(s):
David Charytan, MD, Principal Investigator, Affiliation: Brigham and Women's Hospital

Overall contact:
David Charytan, MD, Phone: 617 52507718, Email: dcharytan@partners.org

This study is a pilot study designed to compare the safety and cardiovascular effects of 26 weeks of combination hydralazine/isorsorbide dinitrate therapy with amlodipine 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 amlopdipine is safe and that it will improve heart function as well blood flow/blood vessel supply.

Official title: A Phase IV Randomized, Double-blind, Active-controlled, Single-center Study of the Safety and Effects on Cardiac Structure and Function of Hydralazine and Isosorbide Dinitrate in Patients With Hemodialysis Dependent ESRD

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Change in mitral annular E' velocity

Change in coronary flow reserve (CFR)

Secondary outcome:

Hypotension

Tolerability

Detailed description: Sixteen patients receiving maintenance hemodialysis will be randomized to 26 weeks of therapy with combination hydralazine/isosorbide dinitrate or amlodipine. Study medications will be titrated to goal dose during the first 4 weeks and maintained at goal dose (as tolerated) between weeks 4-26. A final study visit to assess symptoms after drug discontinuation will occur 4 weeks after drug discontinuation. Study duration-Maximum of 32 weeks with 26 weeks of active therapy.

Efficacy Measures - Tissue Doppler echocardiography and myocardial perfusion scanning using

radioactive NH3 PET will be assessed at weeks 0 and 26. Safety Measures-Adverse events rates including inter- and intra-dialytic hypotension, hyperkalemia,cardiovascular death and gastrointestinal symptoms will be assessed throughout the duration of the study.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

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 systolic blood pressure ≥125 mm Hg

Exclusion Criteria:

- Serum potassium ≥6. 5 mEq/L within 3 past months

- Unscheduled dialysis for hyperkalemia within the past 3 months

- Hypotension defined as pre-dialysis SBP <100 mm Hg within 2 weeks prior to the

baseline visit

- Recurrent intra-dialytic hypotension

- Mitral valve repair or replacement

- Severe mitral valve disease by echocardiography, coronary angiography or cardiac

magnetic resonance imaging

- Known coronary flow defects

- Prior MI

- Prior coronary artery bypass grafting

- Known, non re-vascularized coronary stenosis >90%

- 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, AML)

- Active us of sildenafil, vardenafil or tadalafil

- History of severe aortic stenosis or other cause of LV outflow obstruction

- Pregnancy, anticipated pregnancy, or breastfeeding

- 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)

- asthma

- chronic obstructive pulmonary disease

David Charytan, MD, Phone: 617 52507718, Email: dcharytan@partners.org

Brigham & Women's Hospital, Boston, Massachusetts 02115, United States; Not yet recruiting
David Charytan, MD, Principal Investigator

Starting date: December 2015
Last updated: July 20, 2015