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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04062565
• Other study ID #: 1812168816
• Status: Recruiting
• Phase: Phase 3
• Start date: March 25, 2019
• Est. completion date: December 2021

Study information

• Verified date: August 2019
• Source: University of Arizona
• Contact: Valerie Boss, MS
• Phone: 520-626-8305
• Email: vbloss[@]email.arizona.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Treprostinil Injectable Product
Injection
• Riociguat Pill
Tablet

Locations

Country	Name	City	State
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in stroke volume/end systolic volume (SV/ESV)	Change in stroke volume/end systolic volume (SV/ESV)	Baseline to 3 months
Secondary	Change in pulmonary and cardiac pressures	Increase or decrease in pressures	Baseline to 3 months
Secondary	Change in pulmonary blood flow	Increase or decrease in pulmonary blood flow	Baseline to 3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in brain natriuretic peptide (BNP)	Change in biomarker BNP that examines stretch on the right heart	Baseline to 3 months
Secondary	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
Secondary	Change in Cardio pulmonary Exercise Testing (CPET)	Change in how much oxygen the body consumes at peak exercise	3 months
Secondary	Change in derived VO2 max	Change in how much oxygen the body consumes at peak exercise	3 months
Secondary	Change in derived Ve/VCO2	Change in how much oxygen the body consumes at peak exercise	3 months
Secondary	Change in adverse event profile	Change in side effects or other adverse events between combination therapy and historical control	Baseline to 3 months
Secondary	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