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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Clinical Investigation of Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)

Conditions
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Pulmonary Hypertension Secondary, Heart Failure

Intervention / Treatment
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* Drug: Sodium Nitrite
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Nitrite<br> | Drug: Sodium Nitrite<br>* 40 mg PO (by mouth) TID (three times each day) for 10 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo Oral Capsule<br>* Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) TID (three times each day) for 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and nitrite |  | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in 6-minute walk test | Assessed using Borg dyspnea scale | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite) | 
| Change in right heart catheterization (RHC) hemodynamics | RHC hemodynamic measures will be aggregated to determine if overall hemodynamic are improved over the course of treatment | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite) | 
| Change in severity of heart failure | Determined by NT-proBNP plasma levels | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite) | 
| Change in endurance exercise time |  | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite) | 
| Change in severity of heart failure | Determined by NYHA functional classification changes | 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite) |