Phase 4
Completed N=334
Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
Source: ClinicalTrials.gov NCT00303459 ↗Enrolled (actual)
334
Serious AEs
52.6%
Results posted
Jan 2015
Primary outcomePrimary: Time to First Confirmed Morbidity/Mortality Event up to the End of Study — 96.1; 90.6; 90.5; 83.0 percentage of participants-Kaplan Meier — p=0.2508
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First Confirmed Morbidity/Mortality Event up to the End of Study |
96.1; 90.6; 90.5; 83.0; 82.7; 74.0 | 0.2508 |
| SECONDARY Time to First Confirmed Death, Hospitalization for Worsening or Complication of PAH or Initiation of Intravenous Prostanoids, Atrial Septostomy, or Lung Transplantation |
97.4; 95.3; 94.6; 91.8; 89.6; 88.8 | 0.8385 |
| SECONDARY Change From Baseline to Week 16 in 6 Minute Walk Test (6MWT) |
363; 358; 370; 343; 7.2; -14.6 | 0.0106 sig |
| SECONDARY Number of Participants With Improved, No Change, or Worsened World Health Organisation Functional Class From Baseline to Week 16 |
25; 28; 121; 130; 13; 17 | 1.0000 |
| SECONDARY Time to Death of All Causes From Baseline to End of Study |
99.4; 98.2; 98.7; 95.8; 96.5; 94.0 | 0.4974 |
| SECONDARY Adjusted Percentage Ratio From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-pro-BNP) |
87.46; 110.02; 92.65; 113.20; 85.21; 122.87 | 0.0003 sig |
| SECONDARY Change From Baseline to Week 16 in Borg Dyspnea Index |
3.5; 3.7; 3.4; 3.6; -0.09; -0.08 | 0.9566 |
| SECONDARY Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Questionnaire Calculated Score |
0.678; 0.681; 0.662; 0.645; -0.0161; -0.0361 | 0.5571 |
| SECONDARY Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Visual Analogue Scale Score |
67; 64; 69; 66; 2.1; 2.0 | 0.4086 |
| SECONDARY Patient Global Self Assessment (PGSA) Status at Week 16 |
24; 13; 23; 30; 32; 36 | — |
Eligibility Criteria
Inclusion Criteria
- Signed informed consent prior to initiation of any study-mandated procedure
- 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.
- Patients with symptomatic PAH
- 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
- PAH diagnosed by right heart catheter showing:
- Mean pulmonary arterial pressure (mPAP) >= 25 mm Hg AND
- Pulmonary capillary wedge pressure (PCWP) = 15 mmHg): pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis
- Persistent pulmonary hypertension of the newborn
- 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)
- Restrictive lung disease: total lung capacity (TLC) 1.5 times the upper limit of normal ranges
- Known hypersensitivity or history of drug-related adverse events with bosentan (e.g. increase in liver function test results), or any of the excipients of its formulation
- Receipt of an investigational product other than sildenafil within 3 months before start of study treatment
- Treatment with endothelin receptor antagonists (ERAs), prostanoids or phosphodiesterase (PDE) 5 inhibitors other than sildenafil within 3 months prior to randomization
- Concomitant systemic treatment within 1 week prior to randomization with
- calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus and everolimus
- glibenclamide (glyburide)
- both cytochrome P2C9 (CYP2C9) and cytochrome P3A4 (CYP3A4) (e.g., fluconazole, amiodarone, voriconazole)
- combination of drugs that inhibit CYP2C9 and CYP3A4
- Treatment with nitrates and alpha-blockers at time of randomization
- In the opinion of the investigator - patients in need for treatment with any prostanoid up to Visit 4
- Significant left ventricular dysfunction
Data sourced from ClinicalTrials.gov (NCT00303459). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.