Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction

Completed · Phase 2 · Has a placebo group

Conditions studied: Heart Failure

In brief

A randomized, double-blinded, placebo-controlled crossover study to assess effect of isosorbide mononitrate with dose up-titration on activity tolerance as assessed by (hip-worn, tri-axial) accelerometry.

Key facts

Study ID

NCT02053493

Run by

Adrian Hernandez

People needed

110

Starts

2014-04-01

Expected to finish

2015-03-01

Last updated by the study team

2016-11-28

Who can join

Age: 50 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 50 years
• Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
• Ejection fraction (EF) ≥ 50% as determined on imaging study within 12 months of enrollment with no change in clinical status suggesting potential for deterioration in systolic function
• Stable medical therapy for 30 days as defined by:
• No addition or removal of ACE, Angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists
• No change in dosage of ACE, ARBs, beta-blockers,CCBs or aldosterone antagonists of more than 100%
• One of the following within the last 12 months
• Previous hospitalization for heart failure (HF) with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) or
• Catheterization documented elevated filling pressures at rest (LVEDP≥15 or PCWP≥20) or with exercise (PCWP≥25) or
• Elevated NT-proBNP (> 400 pg/ml) or BNP (> 200 pg/ml) or
• Echo evidence of diastolic dysfunction / elevated filling pressures (at least two) E/A > 1.5 + decrease in E/A of > 0.5 with valsalva Deceleration time ≤ 140 ms Pulmonary vein velocity in systole < diastole (PVs<PVd)sinus rhythm) E/e'≥15 Left atrial enlargement (≥ moderate) Pulmonary artery systolic pressure > 40 mmHg Evidence of left ventricular hypertrophy
• LV mass/BSA ≥ 96 (♀) or ≥ 116 (♂) g/m2
• Relative wall thickness ≥ 0.43 (♂ or ♀) [(IVS+PW)/LVEDD]
• Posterior wall thickness ≥ 0.9 (♀) or 1.0 (♂) cm
• No chronic nitrate therapy or infrequent (≤ 1x week) use of intermittent sublingual nitroglycerin within last 3 months
• Ambulatory (not wheelchair / scooter / walker / cane dependent)
• HF is the primary factor limiting activity as indicated by answering # 2 to the following question:
• My ability to be active is most limited by:
• Joint, foot, leg, hip or back pain
• Shortness of breath and/or fatigue and/or chest pain
• Unsteadiness or dizziness
• Lifestyle, weather, or I just don't like to be active
• Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process (belt designed to fit persons with BMI 20-40 Kg/m2 but belt may fit some persons outside this range)
• Willingness to wear the accelerometer belt for the duration of the trial 11. Willingness to provide informed consent

You may not qualify if…

• Recent (< 3 months) hospitalization for HF
• Hemoglobin < 8.0 g/dl
• Glomerular filtration rate < 20 ml/min/1.73 m2 on most recent clinical laboratories
• SBP < 110 mmHg or > 180 mmHg at consent
• Diastolic blood pressure < 40 mmHg or > 100 mmHg at consent
• Resting HR > 110 bpm at consent
• Previous adverse reaction to nitrates necessitating withdrawal of therapy
• Chronic therapy with phosphodiesterase type-5 inhibitors (intermittent use of phosphodiesterase type-5 inhibitors for erectile dysfunction is allowable if the patient is willing to hold for the duration of the trial)
• Regularly (> 1x per week) swims or does water aerobics
• Significant COPD thought to contribute to dyspnea
• Ischemia thought to contribute to dyspnea
• Documentation of previous EF < 50%
• Acute coronary syndrome within 3 months defined by electrocardiographic changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
• Percutaneous coronary intervention, coronary artery bypass grafting or new biventricular pacing within past 3 months
• Primary hypertrophic cardiomyopathy
• Infiltrative cardiomyopathy (amyloid)
• Constrictive pericarditis or tamponade
• Active myocarditis
• Complex congenital heart disease
• Active collagen vascular disease
• More than mild aortic or mitral stenosis
• Intrinsic (prolapse, rheumatic) valve disease with moderate to severe or severe mitral, tricuspid or aortic regurgitation
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment
• Terminal illness (other than HF) with expected survival of less than 1 year
• Enrollment or planned enrollment in another therapeutic clinical trial in the next 3 months

Where it is running

• Christiana Care Health Services — Newark, Delaware, United States
• Emory University School of Medicine — Atlanta, Georgia, United States
• Northwestern University — Chicago, Illinois, United States
• Johns Hopkins Hospital — Baltimore, Maryland, United States
• Tufts Medical Center — Boston, Massachusetts, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Boston V.A. Healthcare System — West Roxbury, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Duke University Medical Center — Durham, North Carolina, United States
• University Hospitals Case Medical Center — Cleveland, Ohio, United States
• Metro Health System — Cleveland, Ohio, United States
• Cleveland Clinic Foundation — Cleveland, Ohio, United States
• Lancaster General Hospital — Lancaster, Pennsylvania, United States
• University of Pennsylvania Health System — Philadelphia, Pennsylvania, United States
• Jefferson Medical College — Philadelphia, Pennsylvania, United States
• Temple University Hospital — Philadelphia, Pennsylvania, United States
• Michael E Debakey VA Medical Center — Houston, Texas, United States
• University of Utah Hospitals and Clinics — Salt Lake City, Utah, United States
• V.A. Medical Center — Salt Lake City, Utah, United States
• The University of Vermont - Fletcher Allen Health Care — Burlington, Vermont, United States

Full record on ClinicalTrials.gov

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