Overview

This trial is active, not recruiting.

Condition pulmonary arterial hypertension
Treatments bosentan, placebo
Phase phase 4
Sponsor Actelion
Start date May 2006
End date September 2014
Trial size 334 participants
Trial identifier NCT00303459, AC-052-414, COMPASS-2

Summary

COMPASS-2 is a Phase 4, prospective, randomized, double-blind, placebo-controlled, event-driven study evaluating the effect of bosentan on the time to first confirmed morbidity/mortality event in patients with symptomatic PAH already receiving sildenafil therapy. Patients must have been receiving doses of sildenafil equal to or greater than 20 mg t.i.d. for at least 12 weeks prior to being randomized.

The study continued until the predefined target number of morbidity/mortality events was reached.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Bosentan
bosentan
bosentan/62.5 mg tablet/b.i.d. for 4 weeks then bosentan/125 mg tablet/b.i.d.
(Placebo Comparator)
Placebo
placebo
Matching bosentan placebo/b.i.d.

Primary Outcomes

Measure
Time from baseline to first adjudicated morbidity/mortality event
time frame: From baseline to end of study

Secondary Outcomes

Measure
Change from baseline to Week 16 in 6 minute walk test (6MWT)
time frame: From baseline to week 16
Change from baseline to Week 16 in WHO functional
time frame: From baseline to Week 16
Change from baseline to Week 16 in Borg dyspnea index
time frame: From baseline to Week 16
Change from baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) questionnaire
time frame: From baseline to Week 16
Patient Global Self Assessment at Week 16
time frame: Week 16
Time to event for the first occurrence of Death, hospitalization for worsening or complication of PAH or initiation of IV prostanoids, Atrial Septostomy, or Lun Transplantation
time frame: Baseline to end of study
Time to death of all causes from baseline to EOS
time frame: Baseline to End of Study

Eligibility Criteria

Male or female participants at least 12 years old.

Inclusion Criteria: 1. Signed informed consent prior to initiation of any study-mandated procedure 2. Males or females >=12 years of age (except for countries where this age limit is contrary to specific regulatory requirements). - Women of childbearing potential must have a negative pretreatment pregnancy test and must use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination. ·Reliable methods of contraception are: O Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide. O Intrauterine devices. O Oral, transdermal, injectable or implantable contraceptives only in combination with a barrier method. - Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception. - Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception. - Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or documented surgically or naturally sterile. 3. Patients with symptomatic PAH 4. Patients with the following types of PAH belonging to WHO Group I: - Idiopathic (IPAH) - Familial (FPAH) - Associated with (APAH): i. Collagen vascular disease with normal left ventricular function (ejection fraction (EF) > 50%) ii. Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair iii. Drugs and toxins 5. PAH diagnosed by right heart catheter showing: - Mean pulmonary arterial pressure (mPAP) >= 25 mm Hg AND - Pulmonary capillary wedge pressure (PCWP) =< 15 mm Hg or left ventricular end diastolic pressure (LVEDP) =< 15 mmHg If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion. 6. Treatment with a stable dose of sildenafil equal to or greater than 20 mg t.i.d. for at least 12 weeks prior to randomization (no sildenafil dosage adjustment should occur in this period) 7)150 m =< 6MWT =< 480 m, documented by 2 tests with second 6MWT within 15% of first 6MWT distance or a third test required Exclusion Criteria : 1. PAH belonging to WHO group II-V 2. PAH associated with portal hypertension and HIV infection 3. PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy 4. PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg): pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis 5. Persistent pulmonary hypertension of the newborn 6. Significant valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization (i.e. patients with tricuspid or pulmonary insufficiency secondary to PAH can be included) 7. Restrictive lung disease: total lung capacity (TLC) < 60% of normal predicted value (see Appendix 3) 8. Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) < 0.5 9. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C 10. Known HIV infection 11. Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements or that may interfere with the safety or the evaluation of the study, such as chronic infection, chronic renal failure etc. 12. Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements 13. Pregnancy or breast-feeding 14. Condition that prevents compliance with the protocol or adherence to therapy 15. Systolic blood pressure < 85 mmHg 16. Body weight < 40 kg 17. Hemoglobin <75% of the lower limit of the normal range 18. Aspartate aminotransferase (AST) and/or alanine aminotransferase ALT > 1.5 times the upper limit of normal ranges 19. Known hypersensitivity or history of drug-related adverse events with bosentan (e.g. increase in liver function test results [LFTs]), or any of the excipients of its formulation 20. Receipt of an investigational product other than sildenafil within 3 months before start of study treatment 21. Treatment with endothelin receptor antagonists (ERAs), prostanoids or phosphodiesterase (PDE) 5 inhibitors other than sildenafil within 3 months prior to randomization 22. Concomitant systemic treatment within 1 week prior to randomization with - calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus and everolimus - glibenclamide (glyburide) - both CYP2C9 and CYP3A4 (e.g., fluconazole, amiodarone, voriconazole) - combination of drugs that inhibit CYP2C9 and CYP3A4 23. Treatment with nitrates and alpha-blockers at time of randomization 24. In the opinion of the investigator - patients in need for treatment with any prostanoid up to Visit 4 25. Significant left ventricular dysfunction

Additional Information

Official title Effects of Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Morbidity and Mortality in Symptomatic Patients With Pulmonary Arterial Hypertension - A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Prospective, Event Driven Phase IV Study
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by Actelion.