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

Phase 4

Completed

Brief 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.

Detailed Description: Sixteen patients receiving maintenance hemodialysis will be randomized to 26 weeks of therapy with combination hydralazine/isosorbide dinitrate or placebo. 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, ,cardiovascular death and gastrointestinal symptoms will be assessed throughout the duration of the study.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Hydralazine/Isorsorbide Dinitrate	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
Placebo	Placebo	Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.

Primary Outcome Measures

Name	Time	Method
Reduction in Drug Dose or Discontinuation of Study Drug	0 to 6 months	Primary Tolerability measure
Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death	6 months	Rate of primary Safety Outcomes(hypotension, serious adverse events, GI events and CV death)
Change in E' on TDI Echo From 0-6 Months	0 to 6 months	Co-primary efficacy measure measured on Tissue Doppler Echocardiography
Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months	0 to 6 months	Primary Efficacy Measure-CFR measured on rest and stress Positron Emission Tomography
Number of Patients Completing Study From 0 to 6 Months	0 to 6 months	Primary Feasibility Measure

Secondary Outcome Measures

Name	Time	Method
Change in Circulating Fibrosis Markers and Angiogenesis Markers	0 to 6 months	Circulating concentrations of markers such as the carboxy terminal of pro-collagen type 1 or ADMA will be measured
Change in LVMI	0 to 6 months	Change in left ventricular mass index between baseline and 6 months.