Oral Nitrite for Older Heart Failure With Preserved Ejection Fraction

• Status: Completed
• Trial end date: 2018-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized double blinded controlled trial of 20-40 mg sodium nitrite tid in subjects with HFpEF. Primary outcomes are measures of physical function with non-invasive and invasive cardiopulmonary exercise testing, and fatigability, skeletal muscle bioenergetics, serology including inflammatory markers and platelet bioenergetics, quality of life measures.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gladwin, Mark, MD; University of Pittsburgh
• Collaborator: National Institute on Aging (NIA)

Criteria

Inclusion Criteria:

• Age ≥70 years

• Diagnosis of HFpEF [adapted from the 2016 European Society of Cardiology (ESC) Guidelines to include:

1. Prior diagnosis of HF via one of these:

• medical record diagnosis by attending cardiologist

• verbal confirmation of HFpEF with attending cardiologist

• PI review of medical record to confirm HFpEF AND 2. Ejection Fraction % ≥40

• Clinically stable (euvolemic; baseline heart rate <100 bpm) and without hospitalization or invasive cardiac procedure for 6 weeks

• Patients using 81 milligram (mg) aspirin (ASA) will be eligible, but will be asked to hold the medication for 3 days prior to biopsy. This technique has previously been used with consistent safety. Patients will also be asked to avoid non-steroidal anti-inflammatory medications (NSAIDs) for 2 days prior to the biopsy.

• Patients using anti-thrombin and anti-platelet therapy will plan to modify prior to muscle biopsies individually in coordination with the participant's primary cardiologist.

Exclusion Criteria:

• Allergy to lidocaine

• BP >180/95 or <100/60

• Anemia: Hgb<11.0 (♂),10.0 (♀)

• Dementia or inability to give informed consent

• End-stage malignancy

• Severe orthopedic exercise limitation

• Use of chronic oral corticosteroids or other medications that affect muscle function.

• Chronic alcohol or drug dependency.

• Any bleeding disorder that would contraindicate biopsy such as history of clinically significant bleeding diathesis (e.g., Hemophilia A or B, Von Willebrand's Disease or congenital Factor VII deficiency).

• Psychiatric hospitalization within the last 3 months

• Major cardiovascular event or procedure within the prior 6 weeks

• HF secondary to significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction). If valve replacement has been performed, patient may not be enrolled for 12 months after this procedure.

• Severe uncorrected primary valvular heart disease (if valve replacement has been performed, patients will not be eligible for at least 12 months)

• Mechanical valve replacement requiring warfarin

• Peripheral or pulmonary artery disease

• Currently taking clopidogrel for a recent stent placement and/or a complex atherosclerotic lesion such that holding clopidogrel creates disproportionate risk.

• Current use of organic nitrates or phosphodiesterase type 5 inhibitors (PDE5s)

• Unable to hold warfarin or use bridging therapy, or to hold aspirin for 3 days (81 mg), 3 days (325 mg) prior to muscle biopsy or thienopyridine medications for 5 days prior to muscle biopsy.

• Subjects with diabetes whose HgbA1c >10.0

• Other chronic unstable disease such as active neoplasm, end stage chronic kidney, liver or other organ disease,