Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH

NCT ID: NCT04062565

Last Updated: 2025-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-25

Study Completion Date

2025-12-31

Brief Summary

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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

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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).

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental

Treprostinil and Riociguat

Group Type EXPERIMENTAL

Treprostinil Injectable Product

Intervention Type DRUG

Injection

Riociguat Pill

Intervention Type DRUG

Tablet

Interventions

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Treprostinil Injectable Product

Injection

Intervention Type DRUG

Riociguat Pill

Tablet

Intervention Type DRUG

Other Intervention Names

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Remodulin Adempas

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arizona

OTHER

Sponsor Role lead

Responsible Party

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Franz Rischard, DO

Director, University of Arizona Pulmonary Hypertension Program

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Franz Rischard, DO

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Valerie Boss, MS

Role: CONTACT

520-626-8305

Facility Contacts

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Valerie Bloss, MS

Role: primary

520-626-8305

Other Identifiers

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1812168816

Identifier Type: -

Identifier Source: org_study_id

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