Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Registration Number
- NCT04062565
- Lead Sponsor
- University of Arizona
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- 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
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Patients with a mean arterial pressure <60, and/or requiring vasopressor support
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Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable
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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
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Patients with severe restrictive lung disease (FVC<70% predicted) and/or obstructive lung disease (FEV1 <70% predicted and FEV1/FVC <70%).
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Patients with a history of pulmonary embolism within the last three months or evidence of chronic pulmonary embolism.
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Patients with a known contraindication to right heart catheterization.
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Patients whom have received active or previous pulmonary vasoactive medication within the previous 12 weeks.
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PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
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Pulmonary Hypertension belonging to groups 2 to 5 of the WHO classification.
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Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
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Estimated creatinine clearance < 30 mL/min
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Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
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Hemoglobin < 75% of the lower limit of the normal range.
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Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
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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.
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Known concomitant life-threatening disease with a life expectancy < 12 months.
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Body weight < 40 kg and/or >150 kg.
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Any condition that prevents compliance with the protocol or adherence to therapy.
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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.
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Treatment with nitrates of any kind within the 4 weeks prior to enrollment.
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Known hypersensitivity to drugs of the same class as TRE and/or RIO, or any of their excipients.
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Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
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Recent (<6 months) hemoptysis and/or history of severe hemoptysis requiring intervention (bronchial artery embolization).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Riociguat Pill Treprostinil and Riociguat Experimental Treprostinil Injectable Product Treprostinil and Riociguat
- Primary Outcome Measures
Name Time Method Change in stroke volume/end systolic volume (SV/ESV) Baseline to 3 months Change in stroke volume/end systolic volume (SV/ESV)
- Secondary Outcome Measures
Name Time Method Change in pulmonary and cardiac pressures Baseline to 3 months Increase or decrease in pressures
Change in pulmonary blood flow Baseline to 3 months Increase or decrease in pulmonary blood flow
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 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 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
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 Cardio pulmonary Exercise Testing (CPET) 3 months Change in how much oxygen the body consumes at peak exercise
Trial Locations
- Locations (1)
University of Arizona
🇺🇸Tucson, Arizona, United States