Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 5P01HL103455 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Nitrite | Experimental | Study |
|
| Placebo | Placebo Comparator | Control |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Nitrite | Drug | 40 mg PO (by mouth) TID (three times each day) for 10 weeks |
|
| 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 |
| 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. |
Not provided
Inclusion Criteria:
Age 18 years and older
PH-HFpEF confirmed diagnosis by RHC:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Michael Risbano, MD, MA | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
A total of 33 subjects were enrolled and consented with 9 screen failed/ineligible and 24 randomized. Of the 24 randomized, 3 were on drug/placebo but withdrew at a later time, and 21 completed the study.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Nitrite Then Placebo | Sodium Nitrite: 40 mg PO (by mouth) TID (three times each day) for 10 weeks, then crossover to receive placebo for 10 weeks. |
| FG001 | Placebo Then Nitrite | 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, then crossover to receive nitrite for 10 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (10 Weeks) |
|
| ||||||||||||||||||
| Washout (2 Weeks) |
| |||||||||||||||||||
| Second Intervention (10 Weeks) |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Nitrite Then Placebo | Sodium Nitrite: 40 mg PO (by mouth) TID (three times each day) for 10 weeks, then crossover to receive placebo for 10 weeks. |
| BG001 | Placebo Then Nitrite |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | mmHg | Baseline and 10 weeks |
|
From Baseline through study completion, up to 26 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oral Nitrite | Participants who received Oral Nitrite in the first or last 10 weeks of the study. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
This was a small clinical trial that under-enrolled due to the pandemic.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Risbano, Director of Advanced Cardiopulmonary Exercise Testing Program | University of Pittsburgh | 412-692-2210 | risbanomg@upmc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 14, 2022 | Mar 13, 2024 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 |
|
|
| 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 |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
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, then crossover to receive nitrite for 10 weeks.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Sitting Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Sitting Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
|
|
|
| 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | meters | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | mmHg | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | pg/ml | 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. | Posted | Mean | Standard Deviation | mmHg | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Wood Units | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | liters per minute | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. Not all subjects had NYHA Functional class assessed as some subjects missed appointments and some were lost due to the pandemic. | Posted | Count of Participants | Participants | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. This value represents the change in endurance time (difference in time measured while pedaling) from baseline to week 10 during cardiopulmonary exercise testing in minutes. Not all subjects had cardiopulmonary exercise testing performed due to missed visits related to personal health (i.e. fracture, or not feeling well to travel). | Posted | Mean | Standard Deviation | minutes | 10 weeks |
|
|
|
| 0 |
| 24 |
| 0 |
| 24 |
| 22 |
| 24 |
| EG001 | Placebo | Participants who received placebo in the first or last 10 weeks of the study. | 0 | 24 | 0 | 24 | 23 | 24 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Heartburn | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hand,Food, and mouth | Infections and infestations | Systematic Assessment |
|
| Inflammation Right Ear | Infections and infestations | Systematic Assessment |
|
| Volume Overload | Cardiac disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Chest Tightness | Cardiac disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Systolic Murmur | Cardiac disorders | Systematic Assessment |
|
| Dizziness/Lightheadedness | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Earache | Ear and labyrinth disorders | Systematic Assessment |
|
| Inflammation of Ear | Ear and labyrinth disorders | Systematic Assessment |
|
| Vision Disturbance | Eye disorders | Systematic Assessment |
|
| Conjuctivitis | Eye disorders | Systematic Assessment |
|
| Influenza | General disorders | Systematic Assessment |
|
| Swelling of Extremity | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| SARS-CoV-2 Virus | General disorders | Systematic Assessment |
|
| Abscess of tooth | General disorders | Systematic Assessment |
|
| Cramps | General disorders | Systematic Assessment |
|
| Increased Potassium | General disorders | Systematic Assessment |
|
| Cirrhosis | Hepatobiliary disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Joint Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Gout Flare | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle Strain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Increased Respiratory Rate | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Bibasilar Crackles | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Chest Cold | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Stent Procedure (leg) | Vascular disorders | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| D017670 |
| Sodium Compounds |
| Class III |
|
| Class IV |
|