Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)

NCT00303459 | Completed Phase 4 Results DMC

• 2 other identifiers: AC-052-414COMPASS-2
• Study Type: interventional
• Target: 334
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Pulmonary Arterial Hypertension

Keywords

sildenafil; Combination Drug Therapy; bosentan; Pulmonary Hypertension; Pulmonary Arterial Hypertension; Multicenter Study; Antihypertensive Agents; Tracleer; endothelin receptor antagonist; Randomized Controlled Trial; Phosphodiesterase type 5 inhibitor (PDE5i); Outcome Assessment

Outcome Measures

Primary Outcomes (1)

• Time to First Confirmed Morbidity/Mortality Event up to the End of Study

  Kaplan-Meier estimate of percentage of participants without a morbidity/mortality event. A morbidity/mortality event is defined as the occurrence of a) death, b) hospitalization for worsening or complication of PAH or intravenous prostanoid initiation, c) atrial septostomy, d) lung transplantation, or e) worsening PAH, defined as "moderately" or "markedly" worsened PAH symptoms using a patient global self-assessment (PGSA) scale AND initiation of inhaled or subcutaneous prostanoids or the disease progression package (open-label bosentan). If a patient replied "no change" or "mildly worse" on the PGSA, a decrease in 6MWT of 20% versus last visit or 30% versus baseline is also required to confirm the event.

  From baseline to end of study, approximately 86 months

Secondary Outcomes (9)

• Time to First Confirmed Death, Hospitalization for Worsening or Complication of PAH or Initiation of Intravenous Prostanoids, Atrial Septostomy, or Lung Transplantation

  Baseline to end of study, approximately 86 months

• Change From Baseline to Week 16 in 6 Minute Walk Test (6MWT)

  From baseline to week 16

• Number of Participants With Improved, No Change, or Worsened World Health Organisation Functional Class From Baseline to Week 16

  From baseline to Week 16

• Time to Death of All Causes From Baseline to End of Study

  Baseline to End of Study, approximately 86 months

• Adjusted Percentage Ratio From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-pro-BNP)

  Baseline to Month 20

Study Arms (2)

A

EXPERIMENTAL

Bosentan

Drug: bosentan

B

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

bosentan DRUG

bosentan/62.5 mg tablet/b.i.d. for 4 weeks then bosentan/125 mg tablet/b.i.d.

A

placebo DRUG

Matching bosentan placebo/b.i.d.

B

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• PAH belonging to WHO group II-V
• PAH associated with portal hypertension and HIV infection
• PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy
• PAH associated with significant venous or capillary involvement (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) \< 60% of normal predicted value (see Appendix 3)
• Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 0.5
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
• Known HIV infection
• 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.
• Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
• Pregnancy or breast-feeding
• Condition that prevents compliance with the protocol or adherence to therapy
• Systolic blood pressure \< 85 mmHg

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• McLaughlin V, Channick RN, Ghofrani HA, Lemarie JC, Naeije R, Packer M, Souza R, Tapson VF, Tolson J, Al Hiti H, Meyer G, Hoeper MM. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015 Aug;46(2):405-13. doi: 10.1183/13993003.02044-2014. Epub 2015 Jun 25.

  PMID: 26113687 DERIVED

Related Links

• Tracleer for PAH approval page at Drugs@FDA.gov

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jonathan Tolson
• Organization: Actelion Pharmaceuticals Ltd

jonathon.tolson@actelion.com

+41 61 565 56 04

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2006
• First Posted: March 17, 2006
• Study Start: May 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 4, 2025
• Results First Posted: January 26, 2015

Record last verified: 2025-01