CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH (CRUSADE)

CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated Interstitial Lung DiseasE and Pulmonary Hypertension (PH): The CRuSADE PH Study

Patients with interstitial lung disease (ILD) and scleroderma who develop pulmonary hypertension (PH) do not fit well into the current classification system and treatments for pulmonary hypertension. This study aims to better understand patients with ILD-PH and scleroderma and to determine if treatment with Macitentan is beneficial.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension; Interstitial Lung Disease; Scleroderma
• Intervention / Treatment: Drug: Opsumit 10 Mg Tablet

Detailed Description

The investigators aim to use pressure-volume loop derived right ventriculo-vascular coupling, pulmonary impedance, and invasive cardiopulmonary exercise testing (CPET) to:

1. Comprehensively phenotype patients with scleroderma ILD-PH and pulmonary vascular exercise limitation (PVL) relative to scleroderma ILD-PH without PVL.
2. Compare the efficacy of chronic Macitentan therapy in improving 1) right ventricular hemodynamics 2) exercise capacity and 3) symptoms in scleroderma ILD-PH patients with and without PVL.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Valerie Bloss, MS; Phone Number: 520-626-8000; Email: vbloss@email.arizona.edu
• Study Contact Backup: Name: Maria Gordon, MS; Phone Number: 520-626-8000; Email: mgordon@email.arizona.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona
      • Contact: Valerie Bloss, MS; Phone Number: 520-626-8000; Email: vbloss@email.arizona.edu
      • Principal Investigator: Franz P. Rischard, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients who have scleroderma ILD will be defined as having a total lung capacity of less than 80% predicted and CT evidence of fibrosis. The degree of fibrosis will be scored by a radiologist using the CT comparative scoring method of Wells et al (13).
• Pulmonary Hypertension (PH) as defined as resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg with a wedge pressure of ≤ 15 mmHg during right heart catheterization.
• Stable ILD as evident by a stable FEV1 and FVC for 3 months prior to the initiation of the study, and be pulmonary arterial hypertension (PAH)-targeted treatment naïve.

Exclusion Criteria:

• 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<40% predicted) and/or obstructive lung disease (FEV1 <55% predicted and FEV1/FVC <70%).
• Patients with radiographic combined pulmonary fibrosis/emphysema (CPFE) will also be excluded if imaging shows predominant emphysema and/or obstruction is moderately severe (FEV1<30%)
• 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.
• Patients with a contraindication to exercise testing based on American Heart Association/American College of Cardiology (AHA/ACC) guidelines.
• PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
• Persistent pulmonary hypertension of the newborn.
• Pulmonary Hypertension belonging to groups 2 to 5 of the Venice 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.
• Systolic blood pressure < 100 mmHg.
• Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
• Pregnant or breast-feeding.
• Known concomitant life-threatening disease with a life expectancy < 12 months.
• Body weight < 40 kg.
• Any condition that prevents compliance with the protocol or adherence to therapy.
• Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
• Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors).
• Treatment with cytochrome P3A (CYP3A) inducers within 4 weeks prior to randomization
• Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
• Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Opsumit; Opsumit 10 mg tablet by mouth once daily	Drug: Opsumit 10 Mg Tablet; Oral tablet taken once daily; Other Names: Macitentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in exercise pulmonary vascular resistance (PVR)	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in right ventricular pulmonary vascular hemodynamic coupling (RVPA).	Baseline to 6 months
Change in maximal oxygen consumption (V02 max).	Baseline to 6 months
Change in pulmonary impedance.	Baseline to 6 months

Collaborators and Investigators

• Sponsor: Franz Rischard, DO
• Collaborators: University of Pittsburgh; National Jewish Health
• Investigators: Principal Investigator: Franz P. Rischard, DO, University of Arizona

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): January 31, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: October 21, 2018
• First Submitted That Met QC Criteria: October 29, 2018
• First Posted (Actual): October 31, 2018

Study Record Updates

• Last Update Posted (Actual): April 2, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Hypertension; Lung Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Hypertension, Pulmonary; Lung Diseases, Interstitial; Scleroderma, Localized; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: IIS-02801

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No