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	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
Experimental: Sodium Nitrite	Drug: Sodium Nitrite; 40 mg PO (by mouth) TID (three times each day) for 10 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Gladwin, Mark, MD
• 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): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 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