PURPOSE: Reports suggest that patients with PAH have an improved survival if they achieve a 6-minute walk distance (6MWD) >380 m. In order to maximize therapeutic benefit, combination therapy is an option for patients who do not achieve certain therapeutic targets. The primary objective of this study is to determine the percentage of patients that achieve a target 6MWD utilizing a bosentan-based, stepped approach to therapy. A secondary objective is to assess the utility of MRI to monitor cardiac remodeling.
METHODS: COMPASS-3, an open-label, prospective, phase IV study, will enroll 100 patients at 20 centers in the U.S. Inclusion criteria include male and female patients aged >12 years who are symptomatic but naive to advanced PAH therapies. Patients will have PAH with a 6MWD ≥ 200 m and <360 m. Patients will be treated with bosentan monotherapy for 16 weeks (62.5 mg bid, 4 weeks; 125 mg bid, 12 weeks). At week 16, patients will either continue with bosentan monotherapy for an additional 12 weeks or will have sildenafil 20 mg tid added to bosentan if they have not reached a 6MWD ≥ 380 m.
RESULTS: Assessments will include 6MWD, MRI-derived parameters, Borg dyspnea index, echocardiogram parameters, biomarker measurements, right heart catheterization (RHC) parameters, WHO functional class, and patient global self-assessment. To test the validity of cardiac MRI (c-MRI) in PAH, regression analysis will be used to compare changes to standard assessments such as 6-MWD and RHC. Safety and tolerability will be assessed by laboratory tests, vital signs, and reports of adverse events.
CONCLUSION: COMPASS-3 will provide information about the utility of goal-oriented combination treatment. In addition, information on the use of noninvasive c-MRI to monitor the response to treatment will be obtained.
CLINICAL IMPLICATIONS: 1. Patients benefit if a 6MWD ≥380 m is achieved. This might be accomplished with the addition of a second agent if the target distance is not reached with monotherapy. 2. Validation of non-invasive tests (c-MRI) could positively affect patient management.
DISCLOSURE: Fernando Torres, No Product/Research Disclosure Information; Employee Chad McQueen is an employee of Actelion; Consultant fee, speaker bureau, advisory committee, etc. Fernando Torres serves on the speaker bureau for Actelion, Encysive, Gilead and Pfizer. Srinivas Murali serves on the speaker bureau for Actelion, Pfizer and Gilead, and is a consultant for Actelion. Myung Park is a consultant and serves on the speaker bureau and advisory board for Actelion, United Therapeutics and Encysive, serves on the advisory board for Gilead and is a consultant for AstraZeneca; Other Fernando Torres has conducted clinical trials for Actelion. Himanshu Gupta has been an investigator in studies funded by Actelion.