Status: Not yet recruiting
Keywords: Heart Failure , Preserved Ejection Fraction , HFpEF , Nitrates , Activity Tolerance
IRB Number: 00071569
Specialty: Cardiology, Cardiology, Cardiology, Cardiology
Sub Specialties: General Cardiology, Heart Failure, Echocardiography
2.1 Primary Objectives
To evaluate whether isosorbide mononitrate (ISMN), compared to placebo, increases daily activity as assessed by 14-day averaged arbitrary accelerometry units (AAU14).
The primary hypothesis of the NEAT-HFpEF study is that ISMN, compared to placebo will improve daily activity as assessed by AAU14 during the maximally-tolerated dose of study drug (comparison of weeks 5-6 and 11-12).
The significance of this study is that it will provide evidence as to whether nitrate therapy improves symptoms in patients with HFpEF, and thus support or refute guideline recommendations that are based solely on expert opinion.
Secondary Objectives 2.2
1. To evaluate whether ISMN, compared to placebo, improves functional capacity, quality of life (QOL) and natriuretic peptide levels as measured by: Six-minute walk distance (6MWD) (higher with ISMN vs. placebo phase) Borg score during 6-minute walk test (6MWT) (lower with ISMN vs. placebo phase) QOL (Kansas City Cardiomyopathy Questionnaire [KCCQ] score) (higher with ISMN vs. placebo phase) NT-proBNP level (lower with ISMN vs. placebo phase)
2. To evaluate whether ISMN, compared to placebo, improves daily activity as measured by additional accelerometry endpoints: Hours active per day during maximally-tolerated dose of study drug (comparison of weeks 5-6 and 11-12) Slope of daily-averaged arbitrary accelerometry units (AAU) during study drug administration (comparison of weeks 3-6 and 9-12) AUC of daily-averaged AAU during study drug administration (comparison of weeks 3-6 and 9-12)
3. To test the hypothesis that patients will prefer the active drug phase of the study.
Tertiary Objectives 2.3
1. To determine whether the following subgroups of patients that have heart failure (HF) with preserved ejection fraction (HFpEF) derive differential benefit from ISMN:
a) Patients treated or not treated with drugs known to ameliorate nitrate tolerance (renin-angiotensin-aldosterone system [RAAS] antagonists, carvedilol, statins, hydralazine).
b) Patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) above and below the median.
c) Patients with systolic blood pressure (SBP) above and below the median.
d) Patients with or without known coronary artery disease.
2. To determine whether ISMN improves symptoms of HF as determined by the quotient of Borg Score and 6MWD during the 6MWT.
3. To evaluate whether ISMN improves QOL as assessed by the Minnesota Living with HF Questionnaire (MLHFQ).
4. To evaluate whether ISMN increases plasma levels of cyclic guanosine monophosphate (cGMP).
5. To determine whether increasing doses of ISMN are associated with increasing AAU
6. To determine the relationship between accelerometry assessed activity and standard measures of heart failure severity (NYHA class, 6MWD, KCCQ score and NT-proBNP levels) at baseline
7. To determine the relationship between changes in accelerometry assessed activity and changes in standard measures of heart failure severity (NYHA class, 6MWD, KCCQ score and NT-proBNP levels) over the different study periods.
Principal Investigator: Jose Nativi-Nicolau
Co Investigator: Stavros Drakos
Co Investigator: James Fang
Co Investigator: John Ryan
Co Investigator: Edward Gilbert
Co Investigator: Josef Stehlik