CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH (CRUSADE)
Primary Purpose
Interstitial Lung Disease, Scleroderma, Pulmonary Hypertension
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Opsumit 10 Mg Tablet
Sponsored by
About this trial
This is an interventional prevention trial for Interstitial Lung Disease
Eligibility Criteria
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
Sites / Locations
- University of ArizonaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Opsumit
Arm Description
Opsumit 10 mg tablet by mouth once daily
Outcomes
Primary Outcome Measures
Change in exercise pulmonary vascular resistance (PVR)
Secondary Outcome Measures
Change in right ventricular pulmonary vascular hemodynamic coupling (RVPA).
Change in maximal oxygen consumption (V02 max).
Change in pulmonary impedance.
Full Information
NCT ID
NCT03726398
First Posted
October 21, 2018
Last Updated
March 29, 2019
Sponsor
Franz Rischard, DO
Collaborators
National Jewish Health, University of Pittsburgh
1. Study Identification
Unique Protocol Identification Number
NCT03726398
Brief Title
CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH
Acronym
CRUSADE
Official Title
CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated Interstitial Lung DiseasE and Pulmonary Hypertension (PH): The CRuSADE PH Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
January 31, 2020 (Anticipated)
Study Completion Date
December 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Franz Rischard, DO
Collaborators
National Jewish Health, University of Pittsburgh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
The investigators aim to use pressure-volume loop derived right ventriculo-vascular coupling, pulmonary impedance, and invasive cardiopulmonary exercise testing (CPET) to:
Comprehensively phenotype patients with scleroderma ILD-PH and pulmonary vascular exercise limitation (PVL) relative to scleroderma ILD-PH without PVL.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Interstitial Lung Disease, Scleroderma, Pulmonary Hypertension
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Opsumit
Arm Type
Experimental
Arm Description
Opsumit 10 mg tablet by mouth once daily
Intervention Type
Drug
Intervention Name(s)
Opsumit 10 Mg Tablet
Other Intervention Name(s)
Macitentan
Intervention Description
Oral tablet taken once daily
Primary Outcome Measure Information:
Title
Change in exercise pulmonary vascular resistance (PVR)
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Change in right ventricular pulmonary vascular hemodynamic coupling (RVPA).
Time Frame
Baseline to 6 months
Title
Change in maximal oxygen consumption (V02 max).
Time Frame
Baseline to 6 months
Title
Change in pulmonary impedance.
Time Frame
Baseline to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Valerie Bloss, MS
Phone
520-626-8000
Email
vbloss@email.arizona.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Gordon, MS
Phone
520-626-8000
Email
mgordon@email.arizona.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franz P. Rischard, DO
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valerie Bloss, MS
Phone
520-626-8000
Email
vbloss@email.arizona.edu
First Name & Middle Initial & Last Name & Degree
Franz P. Rischard, MD
12. IPD Sharing Statement
Learn more about this trial
CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH
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