Skip to main content
OpenTrials
Completed

NCT Number: NCT03015402

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

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Pulmonary Hypertension Secondary Cardiovascular Diseases Heart Diseases Heart Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sodium Nitrite

Drug

40 mg PO (by mouth) TID (three times each day) for 10 weeks

Other names: study

Placebo oral capsule

Drug

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

Primary outcomes

  1. Mean Pulmonary Artery Pressure (mPAP) During Submaximal Exercise as Compared Between Placebo and Nitrite

    Time frame: Baseline and 10 weeks

    Mean Pulmonary Artery Pressure measurement at submaximal exercise as compared between Placebo and Oral Nitrite at 10 weeks.

Secondary outcomes

  1. Difference in 6-minute Walk Test

    Time frame: 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.

  2. Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Capillary Wedge Pressure

    Time frame: 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.

  3. Change in Severity of Heart Failure

    Time frame: 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.

  4. Change in Right Heart Catheterization (RHC) Hemodynamics - Trans Pulmonary Gradient

    Time frame: 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.

  5. Change in Right Heart Catheterization (RHC) Hemodynamics - Pulmonary Vascular Resistance

    Time frame: 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.

  6. Change in Right Heart Catheterization (RHC) Hemodynamics - Cardiac Output

    Time frame: 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.

  7. Number of Participants With Different Severities of Heart Failure

    Time frame: 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.

  8. Change in Endurance Exercise Time

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

University of Pittsburgh

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

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

Acronym: PH-HFpEF

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Jan 10, 2017
Registry last updated
Jun 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.