Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)

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

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).

Study Overview

• Status: Completed
• Conditions: Heart Failure; Pulmonary Hypertension Secondary
• Intervention / Treatment: Drug: Sodium Nitrite; Drug: Placebo Oral Capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Control	Drug: Placebo Oral Capsule; 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; Other Names: control
Experimental: Sodium Nitrite; Study	Drug: Sodium Nitrite; 40 mg PO (by mouth) TID (three times each day) for 10 weeks; Other Names: study

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in 6-minute Walk Test	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.	Baseline to 10 weeks
Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Capillary Wedge Pressure	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.	During Week 10 follow-up at rest and at exercise
Change in Severity of Heart Failure	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.	Baseline to Week 10
Change in Right Heart Catheterization (RHC) Hemodynamics - Trans Pulmonary Gradient	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Trans Pulmonary Gradient are improved over the course of treatment.	During Week 10 follow-up at rest and at exercise
Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Vascular Resistance	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Pulmonary Vascular Resistance are improved over the course of treatment.	During Week 10 follow-up at rest and at exercise
Change in Right Heart Catheterization (RHC) Hemodynamics - Cardiac Output	Right heart catheterization hemodynamic measures will be aggregated to determine if overall hemodynamic on Cardiac Output are improved over the course of treatment.	During Week 10 follow-up at rest and at exercise
Number of Participants With Different Severities of Heart Failure	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.	10 weeks
Change in Endurance Exercise Time	The endurance exercise time will be measured from the start of loaded pedaling to volitional exhaustion and the worklaod has returned to unloaded pedaling.	10 weeks

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Michael Risbano, MD, MA, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): January 25, 2023
• Study Completion (Actual): January 25, 2023

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimated): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Failure; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: STUDY20010014; 5P01HL103455 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No