Pulmonary Arterial Hypertension
Conditions
Brief summary
The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone
Detailed description
The purpose of this study is to evaluate the combined effect of parenteral treprostinil (TRE) and riociguat (RIO) versus parenteral TRE alone on right ventricular (RV)-pulmonary artery (PA) interaction (RVPA coupling) and global RV function in patients with advanced pulmonary arterial hypertension (PAH).
Interventions
DRUGTreprostinil Injectable Product
Injection
DRUGRiociguat Pill
Tablet
Sponsors
University of Arizona
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will receive Treprostinil 2-3 times per day as tolerated. * Subsequently, participants will receive Riociguat at 0.5 mg taken orally three times a day. * Participants will receive the first dose inpatient prior to discharge. * Participants will continue on a 2 ng/kg/min increase every other day for one week. * Riociguat will subsequently be increased by 0.5 mg taken orally three times a day the following week as tolerated. * Increases in Treprostinil and Riociguat will then alternate weeks such that only one medication is changed per week.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* WHO Category I PAH * Resting mPAP ≥ 25 mmHg with a wedge pressure of ≤ 15mmHg during right heart catheterization. * Need for parenteral TRE as determined by the PH specialist caring for the patient
Exclusion criteria
* Patients with a mean arterial pressure \<60, and/or requiring vasopressor support * Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable * Patients with a left ventricular ejection fraction \<50% or clinical, echocardiographic, and/or catheterization data consistent with heart failure with preserved ejection fraction (HFpEF) and/or moderate-severe aortic or mitral valve abnormality * Patients with severe restrictive lung disease (FVC\<70% predicted) and/or obstructive lung disease (FEV1 \<70% predicted and FEV1/FVC \<70%). * Patients with a history of pulmonary embolism within the last three months or evidence of chronic pulmonary embolism. * Patients with a known contraindication to right heart catheterization. * Patients whom have received active or previous pulmonary vasoactive medication within the previous 12 weeks. * PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis. * Pulmonary Hypertension belonging to groups 2 to 5 of the WHO classification. * Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C. * Estimated creatinine clearance \< 30 mL/min * Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal. * Hemoglobin \< 75% of the lower limit of the normal range. * Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements. * Pregnant or breast-feeding. * Females must either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or * Use 2 medically acceptable, highly effective forms of contraception for the duration of study, and at least 30 after discontinuing study drug. * Known concomitant life-threatening disease with a life expectancy \< 12 months. * Body weight \< 40 kg and/or \>150 kg. * Any condition that prevents compliance with the protocol or adherence to therapy. * Concurrent therapy with strong CYP3A4 inhibitors/inducers (i.e. protease inhibitors, azole antibiotics, macrolides), theophylline, and any medication in the PI's opinion may substantially potentiate the hypotensive effect of RIO. * Treatment with nitrates of any kind within the 4 weeks prior to enrollment. * Known hypersensitivity to drugs of the same class as TRE and/or RIO, or any of their excipients. * Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization. * Recent (\<6 months) hemoptysis and/or history of severe hemoptysis requiring intervention (bronchial artery embolization).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in stroke volume/end systolic volume (SV/ESV) | Baseline to 3 months | Change in stroke volume/end systolic volume (SV/ESV) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in pulmonary blood flow | Baseline to 3 months | Increase or decrease in pulmonary blood flow |
| Change in end-systolic elastance/arterial elastance (Ees/Ea) | Baseline to 3 months | Change in the interaction of the right heart and lung blood vessels |
| Change in Right Ventricle (RV) diastolic stiffness (Beta) | Baseline to 3 months | Change in how stiff the wall of the right heart is at the end of relaxation |
| Change in 6 minute walk distance | Baseline to 3 months | Change in how far a participant can walk during a self paced 6 minute walk test |
| Change in brain natriuretic peptide (BNP) | Baseline to 3 months | Change in biomarker BNP that examines stretch on the right heart |
| Change in pulmonary and cardiac pressures | Baseline to 3 months | Increase or decrease in pressures |
| Change in Cardio pulmonary Exercise Testing (CPET) | 3 months | Change in how much oxygen the body consumes at peak exercise |
| Change in derived VO2 max | 3 months | Change in how much oxygen the body consumes at peak exercise |
| Change in derived Ve/VCO2 | 3 months | Change in how much oxygen the body consumes at peak exercise |
| Change in adverse event profile | Baseline to 3 months | Change in side effects or other adverse events between combination therapy and historical control |
| Change in composite time to clinical worsening | Baseline to 3 months | Difference relative to historical control in the time from diagnosis to followup, hospitalization, death or transplant |
| Change in magnetic resonance imaging (MRI) right ventricle volumes | Baseline to 3 months | Change in the volume ejected per beat and the end systolic and diastolic values of the right heart |
Countries
United States
Contacts
Primary ContactValerie Boss, MS
Outcome results
None listed