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)

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Treprostinil Injectable Product; Drug: Riociguat Pill

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).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Valerie Boss, MS; Phone Number: 520-626-8305; Email: vbloss@email.arizona.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona
      • Principal Investigator: Franz Rischard, DO
      • Contact: Valerie Bloss, MS; Phone Number: 520-626-8305; Email: vbloss@email.arizona.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Treprostinil and Riociguat	Drug: Treprostinil Injectable Product; Injection; Other Names: Remodulin; Drug: Riociguat Pill; Tablet; Other Names: Adempas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in stroke volume/end systolic volume (SV/ESV)	Change in stroke volume/end systolic volume (SV/ESV)	Baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary and cardiac pressures	Increase or decrease in pressures	Baseline to 3 months
Change in pulmonary blood flow	Increase or decrease in pulmonary blood flow	Baseline to 3 months
Change in end-systolic elastance/arterial elastance (Ees/Ea)	Change in the interaction of the right heart and lung blood vessels	Baseline to 3 months
Change in Right Ventricle (RV) diastolic stiffness (Beta)	Change in how stiff the wall of the right heart is at the end of relaxation	Baseline to 3 months
Change in 6 minute walk distance	Change in how far a participant can walk during a self paced 6 minute walk test	Baseline to 3 months
Change in brain natriuretic peptide (BNP)	Change in biomarker BNP that examines stretch on the right heart	Baseline to 3 months
Change in magnetic resonance imaging (MRI) right ventricle volumes	Change in the volume ejected per beat and the end systolic and diastolic values of the right heart	Baseline to 3 months
Change in Cardio pulmonary Exercise Testing (CPET)	Change in how much oxygen the body consumes at peak exercise	3 months
Change in derived VO2 max	Change in how much oxygen the body consumes at peak exercise	3 months
Change in derived Ve/VCO2	Change in how much oxygen the body consumes at peak exercise	3 months
Change in adverse event profile	Change in side effects or other adverse events between combination therapy and historical control	Baseline to 3 months
Change in composite time to clinical worsening	Difference relative to historical control in the time from diagnosis to followup, hospitalization, death or transplant	Baseline to 3 months

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Principal Investigator: Franz Rischard, DO, University of Arizona

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Activators; Treprostinil; Riociguat
• Other Study ID Numbers: 1812168816

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No