Clinical trial NCT01516346
Conditions: Heart Failure Congestive Heart Failure
Keywords: Heart Failure Heart failure with preserved ejection fraction (HFpEF) Vasodilators Isosorbide dinitrate Hydralazine wave reflections arterial stiffness hemodynamics
Sponsor: Corporal Michael J. Crescenz VA Medical Center
Start date: 2012-01-01; Completion date: 2017-08-18
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.

Detailed description:

Arms: arm 1: Research pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain placebo capsules.

Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. arm 2: Research pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain the active ingredient Hydralazine.

Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks.

Dosage of Hydralazine will be 37.5mg (if Stage 1) OR 75mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. arm 3: Research pharmacy-formulated capsules will be given to subjects in two bottles. For this interventional arm, both the bottles will contain placebo capsules.

Dosage will be same regardless of up-titration from Stage 1 dosing to Stage 2 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks.
Interventions: intervention 1: Isosorbide Dinitrate intervention 2: Isosorbide Dinitrate + Hydralazine intervention 3: Placebo
Intervention descriptions: intervention 1: Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 placebo capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. intervention 2: Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 hydralazine capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. Subjects receiving hydralazine will be given 37.5mg PO q8am, 2pm, and 8pm and will be titrated up to 75mg PO q8am, 2pm, and 8pm. intervention 3: Enrolled subjects will be randomized in a blinded fashion to 2 placebo capsules TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs.

Protocol documents: