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

Heart Failure Clinical Trial

— PH-HFpEF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03015402
• Other study ID #: STUDY20010014
• Secondary ID: 5P01HL103455
• Status: Completed
• Phase: Phase 2
• Start date: October 30, 2017
• Est. completion date: January 25, 2023

Study information

• Verified date: June 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 25, 2023
• Est. primary completion date: January 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension Secondary

Intervention

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

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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