Clinical Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument
- Registration Number
- NCT01841762
- Lead Sponsor
- Actelion
- Brief Summary
SYMPHONY is prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study of the PAH-SYMPACT, a new quality of life questionnaire for patients with pulmonary arterial hypertension. Patients will be in the study for 5 1/2 months, 4 months of which they will receive macitentan, 10 mg, once daily.
The primary objectives are to demonstrate the final content validity of the PAH SYMPACT instrument, to demonstrate the psychometric characteristics of reliability and construct validity of the PAH-SYMPACT instrument, and to demonstrate the ability of the PAH SYMPACT instrument to detect change. The secondary objective is to assess the safety of macitentan in patients with pulmonary arterial hypertension. The exploratory objective is to explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT) in patients with pulmonary arterial hypertension.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 284
-
Signed informed consent prior to initiation of any study mandated procedure
-
Patients with symptomatic PAH in World Health Organization (WHO) Functional Class (FC) II to IV
-
Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:
- Idiopathic, or
- Heritable, or
- Drug or toxin induced, or
- Associated with one of the following:
i. Connective tissue disease ii. Congenital heart disease with simple systemic-to-pulmonary shunt at least one year after surgical repair iii. HIV infection
-
Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:
- Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
- Resting pulmonary vascular resistance (PVR) > 240 dyn•s•cm-5 and
- Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg
-
6-minute walk distance (6MWD) ≥ 150 m at Screening
-
Able to fluently speak and read English
-
For patients on phosphodiesterase type-5 inhibitors (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers, stable doses for at least 3 months prior to Visit 2
-
For patients on oral diuretics, stable doses for at least 4 weeks prior to Visit 2
-
Men or women aged 18 or older
-
A woman is considered to be of childbearing potential unless she:
- Has not yet entered puberty, or
- Does not have a uterus, or
- Has gone through menopause (has not had a period for at least 12 months for natural reasons, or who has had their ovaries removed)
-
A women of childbearing potential is eligible only if she meets both criteria below:
- Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
- Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
-
- Moderate to severe obstructive lung disease: forced expiratory volume in one second (FEV1) / forced vital capacity < 70% and FEV1 < 65% of predicted value after bronchodilator administration
- Moderate to severe restrictive lung disease: total lung capacity < 60% of predicted value
- Hemoglobin < 75% of the lower limit of the normal range at screening
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN) at screening
- Estimated creatinine clearance < 30 mL/min at screening
- Systolic blood pressure (SBP) < 90 mmHg at screening
- Body weight < 40 kg at screening
- Known concomitant life-threatening diseases with a life expectancy of < 12 months
- Any condition that prevents compliance with the protocol or adherence to therapy
- Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial
- Treatment with intravenous or subcutaneous prostacyclin or prostacyclin analogs within 3 months prior to Visit 2, or scheduled to receive any of these compounds during the trial
- Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
- Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
- Recently started (< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise
- Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study
- Known hypersensitivity to macitentan or its excipients or drugs of the same class
- Treatment with another investigational drug within 3 months prior to Visit 2
- Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Macitentan Macitentan Macitentan tablet, dose of 10 mg, once daily
- Primary Outcome Measures
Name Time Method Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT) From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16) Content validity of the PAH-SYMPACT was assessed using item performance, exploratory and confirmatory factor analysis. The final item content and domain structure of PAH-SYMPACT was determined based on these analyses from the Steering Committee (expert clinicians) and findings from the qualitative research done with patients previously.
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability. From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period. The reliability of the PAH-SYMPACT is assessed by internal consistency reliability. This was determined using Cronbach's alpha-a value on an internal level scale from 0 to 1.0 with higher scores indicating a more-reliable (precise) instrument.
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability. From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period. The reliability of the PAH-SYMPACT is assessed by test-retest reliability. Intra-class correlation coefficients (ICCs) assess test-retest reliability for the symptom and impact part scores as well as domains. ICCs equal to or greater than 0.70 are considered to demonstrate good test-retest reliability for total and domain scores.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits) From Day 1 (Baseline Visit) to End of Study visit (EoS). Safety events are reported and documented as defined in study protocol.
Trial Locations
- Locations (80)
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Ferrell-Duncan Clinic
🇺🇸Springfield, Missouri, United States
UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Advocate Health and Hospitals Corporation
🇺🇸Oakbrook Terrace, Illinois, United States
Scott & White Memorial Hospital
🇺🇸Temple, Texas, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
VAGLAHS, VA Greater LA Healthcare System
🇺🇸Los Angeles, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Florida Academic Health Center
🇺🇸Gainesville, Florida, United States
Cedars-Sinai Medical Center
🇺🇸Beverly Hills, California, United States
Georgia Clinical Research
🇺🇸Austell, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Los Angeles Biomedical Research Institute
🇺🇸Torrance, California, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Veritas Clinical Specialties
🇺🇸Topeka, Kansas, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
UCSD Medical Center, Pulmonary Department
🇺🇸La Jolla, California, United States
University of Florida College of Medicine, Jacksonville
🇺🇸Jacksonville, Florida, United States
Iowa City Heart Center
🇺🇸Iowa City, Iowa, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Pulmonary Associates, PA
🇺🇸Phoenix, Arizona, United States
Bay Area Cardiology Associates, P.A.
🇺🇸Brandon, Florida, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Kentuckiana Pulmonary Associates
🇺🇸Louisville, Kentucky, United States
University of Chicago Medical
🇺🇸Chicago, Illinois, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Nebraska Pulmonary Specialties
🇺🇸Lincoln, Nebraska, United States
North Shore-LIJ/Advance Lung Disease Clinic
🇺🇸New Hyde Park, New York, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Pulmonary and Critical Care Associates
🇺🇸Union, New Jersey, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Wellspan Lung, Sleep and Critical Care
🇺🇸York, Pennsylvania, United States
University of Wisconsin School of Medicine and Public Health
🇺🇸Madison, Wisconsin, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Cardiovascular Associates of the Southeast, LLC
🇺🇸Birmingham, Alabama, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
UCSF Fresno
🇺🇸Fresno, California, United States
Stanford University
🇺🇸Stanford, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Medstar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Chest Infectious Diseases and Critical Care Associates, PC
🇺🇸Des Moines, Iowa, United States
Mercy Clinic Pulmonology
🇺🇸Saint Louis, Missouri, United States
Beaumont Hospital
🇺🇸Troy, Michigan, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Midwest Pulmonary Consultants
🇺🇸Kansas City, Missouri, United States
Clayton Sleep Institute
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Montefiore Medical Center, Weiler Division
🇺🇸Bronx, New York, United States
UC Health/University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Novant Health Pulmonary and Critical Care
🇺🇸Matthews, North Carolina, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Davis Heart & Lung Research Institute
🇺🇸Columbus, Ohio, United States
CDA for Oregon Pulmonary Associate
🇺🇸Portland, Oregon, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Thomas Jefferson University, Division on Pulmonary and Critical Care
🇺🇸Philadelphia, Pennsylvania, United States
Berks Schuylkill Respiratory Specialists, Ltd.
🇺🇸Wyomissing, Pennsylvania, United States
Temple Lung Center
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Sioux Falls Cardiovascular, PC
🇺🇸Sioux Falls, South Dakota, United States
Baylor Research Institute (BRI)
🇺🇸Dallas, Texas, United States
Sentara Norfolk General Hospital
🇺🇸Norfolk, Virginia, United States
Inova Heart and Vascular Institue / Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Pulmonary & Sleep Research
🇺🇸Spokane, Washington, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Aurora Cardiovascular Services
🇺🇸Milwaukee, Wisconsin, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States