Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD
Condition: Chronic Hemodialysis (ESRD)
MeSH terms: Kidney Failure, Chronic
Intervention: Hydralazine/Isorsorbide Dinitrate; Placebo
Intervention description: 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 titration will mimic titration of active study arm
Intervention MeSH terms: Hydralazine
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: hemodialysis; ESRD; Cardiovascular Disease; Isosorbide Dinitrate; Hydralazine

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

          1. Maintenance hemodialysis therapy for end-stage renal disease

          2. Age 18-85 years

          3. ≥ 90 days since dialysis initiation

          4. Ability to provide informed consent

          5. 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

          1. Serum potassium ≥6.5 mEq/L within 2 months prior to screening

          2. Unscheduled dialysis for hyperkalemia within the 3 months prior to screening

          3. Hypotension defined as pre-dialysis SBP <100 mm Hg (seated measurement) within 4 weeks
             prior to enrollment

          4. 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.

          5. Mitral valve repair or replacement

          6. Severe mitral valve disease by echocardiography, coronary angiography or cardiac
             magnetic resonance imaging

          7. Prior coronary artery bypass graft

          8. Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another
             dialysis unit within 6 months

          9. Expected survival < 6 months

         10. Allergy to study medications (ISD, HY, adenosine/diprimidole)

         11. Active use of sildenafil, vardenafil or tadalafil

         12. History of severe aortic stenosis or other cause of LV outflow obstruction

         13. Pregnancy, anticipated pregnancy, or breastfeeding, confirmed by serum pregnancy test
             on the day of PET scan

         14. Incarceration

         15. Participation in another intervention study

         16. Use of monoamine oxidase inhibitors

         17. 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

         18. Active use of any of the study medications unless participant and physician willing to
             discontinue prior to enrollment.