Clinical trial NCT03888365: Patient Global Impression Questions for Activity-Induced Symptoms in Participants With PAH
Official title: An Observational Study to Characterize Patient Global Impression Questions for Activity-induced Symptoms in Patients With Pulmonary Arterial Hypertension (PAH)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Arterial Hypertension
Keywords: Hypertension
Treprostinil
Pulmonary Hypertension
Lung Diseases
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Lung Biotechnology PBC
First posted: 2019-03-25
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Males and females aged 18 years and above with a diagnosis of PAH that is either idiopathic or familial PAH (World Health Organization \[WHO\] Group 1), collagen vascular disease associated PAH, PAH associated with human immunodeficiency virus (HIV) infection, PAH induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 years).

Brief summary: This is an observational, multicenter, single-day, Phase 2 study. This study will include a 14-day Screening Period and Study Day 1 clinic visit. Participants will be required to perform an activity to induce symptoms of PAH, and participants' severity of self-reported symptoms of PAH will be measured from pre-activity, immediately after the activity, and through the 30-minute recovery. Participants will be asked about their PAH symptoms using 3 PGI-S questions that address their overall PAH symptoms, shortness of breath, and physical fatigue.

Detailed description: This is an observational, multicenter, single-day, Phase 2 study. This study will include a 14-day Screening Period and Study Day 1 clinic visit. Participants will be required to perform an activity to induce symptoms of PAH, and participants' severity of self-reported symptoms of PAH will be measured from pre-activity, immediately after the activity, and through the 30-minute recovery. Participants will be asked about their PAH symptoms using 3 Patient Global Impression of Severity (PGI-S) questions that address their overall PAH symptoms, shortness of breath, and physical fatigue.

PAH symptoms will be induced via the Incremental Shuttle Walk Test (ISWT). The ISWT used in this study required the participant to walk back and forth on a 10-meter course. The total number of shuttles completed by a participant during the Screening ISWT will be the maximum targeted for that participant during the remaining ISWTs in the study.

After Screening, participants will be assigned to 1 of 2 cohorts based on PAH medications as prescribed by their physician: Cohort A will include participants who are currently prescribed and using inhaled treprostinil for the treatment of PAH and Cohort B will include participants who are taking other PAH medications (instead of inhaled treprostinil).

The study also includes 2 periods. One period for participants in Cohort A (Treprostinil Users), included an ISWT initiated within 30 minutes of the previous dose (expected peak level) and the other period included an ISWT within 3 to 4 hours of the previous dose of inhaled treprostinil (expected trough level). Participants in Cohort B (Non-Treprostinil Users), an ISWT will be initiated approximately 4 hours after the morning dose of PAH medication (Period 1) and an ISWT initiated at least 1 hour following completion of the previous ISWT (Period 2). Participants will be provided at least a 1-hour period for rest between ISWTs (until participant feels they are rested enough to perform again at their baseline level) prior to Period 2 assessments.

Eligibility criteria: Inclusion Criteria:

1. Participant voluntarily gives informed consent to participate in the study.
2. Males and females aged 18 years and above at the time of informed consent.
3. Established primary diagnosis of PAH that is either idiopathic or familial PAH (WHO Group 1), collagen vascular disease associated PAH, PAH associated with HIV infection, PAH induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 years).
4. Participant is deemed WHO Functional Class 1, 2, or 3.
5. Participant has shortness of breath upon exertion (exhibits a ≥1-point change in Borg dyspnea score) as assessed by the ISWT and a minimum completion of 3 shuttles (30 meters) of the ISWT. Participant may have other symptoms as well.
6. Participant is on stable dose of all FDA-approved PAH treatments (exceptions are anticoagulants and diuretics) for at least 60 days prior to Screening.
7. In the opinion of the Investigator, the participant can communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements.

Exclusion Criteria:

1. The participant is known to be pregnant or nursing.
2. The participant has PAH related to any condition not covered under inclusion criteria, including, but not limited to, pulmonary venous hypertension, pulmonary venoocclusive disease, pulmonary capillary hemangiomatosis, chronic thromboembolic pulmonary hypertension, or other conditions under WHO Group 2, 3, 4, and 5 classifications.
3. The participant has evidence of clinically significant left-sided heart disease (including, but not limited to, left ventricular ejection fraction \<40%, left ventricular hypertrophy) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease.
4. The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
5. The participant has any ambulatory or orthopedic limitations that would interfere with the ability to perform the activity.
6. The participant has been hospitalized within 30 days of Screening.
7. Current use of prostacyclin analogs/agonists, except inhaled treprostinil, for the treatment of PAH.
8. Use of any other investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days of Screening (concurrent participation in registry studies is allowed).
9. Any other clinically significant illness that, in the opinion of the Investigator, might put the participant at risk of harm during the study or might adversely affect the interpretation of the study data.

Primary outcomes:
measure: Change From Baseline in Patient Global Impression of Severity (PGI-S) Score in Cohort A Participants at Approximately 30 Minutes of Previous Dose of Inhaled Treprostinil (the Expected Peak Level) on Day 1
timeFrame: Baseline, Approximately 30 m of previous dose of inhaled treprostinil (the expected peak level) on Day 1
measure: Change From Baseline in PGI-S Score in Cohort A Participants at Approximately 3-4 Hours of Previous Dose of Inhaled Treprostinil (the Expected Trough Level) on Day 1
timeFrame: Baseline, Approximately 3-4 h of previous dose of inhaled treprostinil (the expected trough level) on Day 1
measure: Change From Baseline in PGI-S Score in Cohort B Participants at Approximately 4 Hours After Morning Dose of Non-Treprostinil PAH Medication (Period 1) on Day 1
timeFrame: Baseline, Approximately 4 h after morning dose of non-treprostinil PAH medication (Period 1) on Day 1
measure: Change From Baseline in PGI-S Scores in Cohort B Participants With an ISWT at Least 1 h Following Completion of Previous ISWT (Period 2) on Day 1
timeFrame: Baseline, At least 1 h following completion of previous ISWT (Period 2) on Day 1
Secondary outcomes:
measure: Change From Baseline in Modified Borg Dyspnea Scores at Day 1
timeFrame: Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1
Other outcomes:
measure: Change From Baseline in Pulse Oximetry at Day 1
timeFrame: Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1
measure: Change From Baseline in Heart Rate at Day 1
timeFrame: Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Pulmonary Associates
state: California
city: Clearwater
country: United States
facility: St. Francis Sleep, Allergy & Lung Institute
state: Florida
city: Atlanta
country: United States
facility: Pulmonary & Critical Care of Atlanta
state: Georgia
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Fayetteville
country: United States
facility: Pulmonary Health Physicians, PC
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
References: