RECRUITINGPhase 3INTERVENTIONAL
Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH
A Prospective Trial to Evaluate Up-front Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Patients With Advanced Pulmonary Arterial Hypertension (IIR-3810)
About This Trial
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
Who May Be Eligible (Plain English)
Who May Qualify:
- 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
Who Should NOT Join This Trial:
- 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
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
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).
Treatments Being Tested
DRUG
Treprostinil Injectable Product
Injection
DRUG
Riociguat Pill
Tablet
Locations (1)
University of Arizona
Tucson, Arizona, United States