Pulmonary Arterial Hypertension
Conditions
Brief summary
The purpose of this study is to see if the drug sotatercept given for 36 weeks improves the functioning of the heart and improves quality of life.
Interventions
DRUGSotatercept
As per FDA indications, sotatercept will be administered as 0.3 mg/kg injection for the first dose followed by 0.7 mg/kg injections for subsequent doses.
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * NYHA Class II-IV. * LVEF ≥ 40 % within the preceding year. * No recent initiation of pulmonary vasodilator in the last 60 days. * Pulmonary arterial hypertension by right heart catheterization (Mean PA pressure ≥ 20 mmHg with PVR\>2 Wood units) with no evidence of heart failure with preserved ejection fraction (exercise PCWP \<25 mm Hg). * Symptomatic PAH patients with plan to undergo exercise RHC for reassessment of exertional symptoms.
Exclusion criteria
* Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening. * Planned coronary, carotid, or peripheral artery revascularization. * Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, anemia, or more than moderate mitral or aortic heart valve disease). * Wheelchair bound or orthopedic inability to exercise. * Chronic hypoxemia with inability to exercise without oxygen supplementation. * Skeletal muscle myopathy. * History of rhabdomyolysis. * Participation in any clinical trial of an approved or non-approved device for the treatment of pulmonary hypertension within 30 days before screening. * Receipt of any investigational medicinal product within 30 days before screening. * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. * Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator. * Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary arterial mean pressure/Cardiac Output (PA/CO) at peak exercise | Baseline, Week 24 | Peak exercise pulmonary arterial mean pressure/ Cardiac output (mm Hg/L/min) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Consumption (VO2) | Baseline, 24 weeks | VO2 will be measured in mL/kg/min. It will be directly measured using expired gas analysis. |
| Single leg blood flow at peak exercise | Baseline, 24 weeks | Single leg blood flow will be obtained from venous access. Single leg blood flow will be measured in ml/min |
| Pulmonary vascular resistance at rest | Baseline, 24 weeks | Pulmonary vascular resistance will be measured in Wood units (mmHg/L/min) |
| Pulmonary vascular resistance at peak exercise | Baseline, 24 weeks | Pulmonary vascular resistance will be measured in Wood units (mmHg/L/min) |
| Pulmonary arterial (PA) compliance at rest | Baseline, 24 weeks | PA compliance measures pulmonary arterial distensibility and will be recorded at Baseline and 24 Weeks. PA compliance will be measured in ml/mm Hg. |
| Pulmonary arterial (PA) compliance at peak exercise | Baseline, 24 weeks | PA compliance measures pulmonary arterial distensibility and will be recorded at Baseline and 24 Weeks. PA compliance will be measured in ml/mm Hg. |
| Pulmonary arterial elastance at rest | Baseline, 24 weeks | PA elastance measures pulmonary artery stiffness and will be recorded at baseline and 24 weeks as PA systolic pressure/stroke volume (units mm Hg/ml) |
| Pulmonary arterial elastance at peak exercise | Baseline, 24 weeks | PA elastance measures pulmonary artery stiffness and will be recorded at baseline and 24 weeks as PA systolic pressure/stroke volume (units mm Hg/ml) |
| Left ventricular (LV) transmural pressure at rest | Baseline, 24 weeks | LV transmural pressure will measured by catheterization at Baseline and 24 Weeks as the difference between pulmonary capillary wedge pressure and right atrial pressure |
| Left ventricular (LV) transmural pressure at peak exercise | Baseline, 24 weeks | LV transmural pressure will measured by catheterization at Baseline and 24 Weeks as the difference between pulmonary capillary wedge pressure and right atrial pressure |
| Right Ventricular Pulmonary Artery Coupling at rest | Baseline, 24 weeks | Calculated as the ratio of RV function by echocardiography indexed to PA systolic pressure (unit mmHg-1) |
| Right Ventricular Pulmonary Artery Coupling at peak exercise | Baseline, 24 weeks | Calculated as the ratio of RV function by echocardiography indexed to PA systolic pressure (unit mmHg-1) |
| Eccentricity index at rest | Baseline, 24 weeks | Eccentricity index will be calculated as the ratio of antero posterior and septolateral dimension of the left ventricle by echocardiogram |
| Eccentricity index at peak exercise | Baseline, 24 weeks | Eccentricity index will be calculated as the ratio of antero posterior and septolateral dimension of the left ventricle by echocardiogram |
| Right atrial pressure (RA) at rest | Baseline, 24 weeks | RA pressure (mm Hg) will be measured by catheterization conducted at Baseline and 24 weeks |
| Right atrial pressure (RA) at peak exercise | Baseline, 24 weeks | RA pressure (mm Hg) will be measured by catheterization conducted at Baseline and 24 weeks |
| Change in skeletal muscle O2 diffusive conductance (Dm) during peak exercise | Baseline, 24 weeks | Dm is measured in ml/mm Hg/min during peak exercise |
| Change in skeletal muscle O2 diffusive conductance (Dm) during single leg exercise | Baseline, 24 weeks | Dm is measured in ml/mm Hg/min during single leg exercise |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYogesh Reddy, MBBS
Mayo Clinic
Outcome results
None listed