Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction

Phase 2

Completed

Conditions: Pulmonary Hypertension Secondary
Heart Failure

Interventions: Drug: Sodium Nitrite
Drug: Placebo Oral Capsule

Registration Number: NCT03015402

Lead Sponsor: University of Pittsburgh

Brief Summary: The main objective of this study is to determine the clinical efficacy of oral inorganic nitrite verses placebo and the therapeutic response with regards to exercise tolerance in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

Detailed Description: This is a single-center, 22-week double-blind, randomized placebo-controlled cross-over trial of oral nitrite on exercise capacity and hemodynamic measurements in subjects with PH-HFpEF.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

Inclusion Criteria

Age 18 years and older

PH-HFpEF confirmed diagnosis by RHC:

Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mmHg AND
Pulmonary capillary wedge pressure (PWCP) ≥ 15 mmHg AND
Transpulmonary Gradient (TPG) ≥ 12 mmHg

Exclusion Criteria

Age less than 18 years;
SBP > 170 or < 110 mmHg
DBP >95 or < 60 mmHg
Hemoglobin A1C > 10
Positive urine pregnancy test or breastfeeding;
Ejection Fraction (EF) < 40%;
Dementia
End-stage malignancy
Major cardiovascular event or procedure within 6 weeks prior to enrollment
Severe valvular disease
Known chronic psychiatric or medical conditions that may increase the risk associated with study participation in the judgment of the investigator, would make the subject inappropriate for entry into this study;
Smoker
Hemoglobin <9 g/dL
Serum creatinine > 3.0 mg/dL
Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days; RHC < 2 weeks from study screening RHC unless clinically indicated

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sodium Nitrite	Sodium Nitrite	Study
Placebo	Placebo Oral Capsule	Control

Primary Outcome Measures

Name	Time	Method
Mean Pulmonary Artery Pressure (mPAP) During Submaximal Exercise as Compared Between Placebo and Nitrite	Baseline and 10 weeks	Mean Pulmonary Artery Pressure measurement at submaximal exercise as compared between Placebo and Oral Nitrite at 10 weeks.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Different Severities of Heart Failure	10 weeks	Determined by NYHA functional classification changes. Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. While the change in severity of heart failure is listed as an end point, since this is ordinal data we cannot provide a p-value. We present the NYHA data at screening, crossover and 10 weeks.
Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Capillary Wedge Pressure	During Week 10 follow-up at rest and at exercise	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Pulmonary Capillary Wedge Pressure are improved over the course of treatment.
Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Vascular Resistance	During Week 10 follow-up at rest and at exercise	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Pulmonary Vascular Resistance are improved over the course of treatment.
Change in Endurance Exercise Time	10 weeks	The endurance exercise time will be measured from the start of loaded pedaling to volitional exhaustion and the worklaod has returned to unloaded pedaling.
Change in Severity of Heart Failure	Baseline to Week 10	Determined by N-terminal pro b-type natriuretic peptide (NT-proBNP) plasma levels. The number of subjects with available NT-proBNP values do not match the total number in the study as several subjects missed visit timepoints due to health issues resulting in NT-proBNP not being obtained.
Difference in 6-minute Walk Test	Baseline to 10 weeks	The 6-minute walk test measures the distance an individual is able to walk over 6 minutes on a hard, flat surface. The subject is allowed to self-pace and rest as needed. The number of subjects with available 6-minute walk tests do not match the total number of subjects in the study due to: one subject fracturing a foot and several subjects missing visit timepoints due to health issues resulting in 6 minute walk test not being performed.
Change in Right Heart Catheterization (RHC) Hemodynamics - Trans Pulmonary Gradient	During Week 10 follow-up at rest and at exercise	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Trans Pulmonary Gradient are improved over the course of treatment.
Change in Right Heart Catheterization (RHC) Hemodynamics - Cardiac Output	During Week 10 follow-up at rest and at exercise	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Cardiac Output are improved over the course of treatment.