Combination Therapy in Pulmonary Arterial Hypertension

NCT00433329 | Completed Phase 4 Results

• 1 other identifier: AC-052-419
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

An open label, non-comparative study design is appropriate for this Phase 4 study designed to assess whether a core therapy of bosentan, either as monotherapy or with the addition of sildenafil, enables patients with pulmonary arterial hypertension (PAH) to achieve a 6-minute walk distance (6 MWD) of ≥380 meters after 28 weeks of therapy This design is also appropriate to pioneer the utility of cardiac MRI in assessing improved functional capacity in PAH and exploring its correlation with other parameters.

Conditions

Pulmonary Arterial Hypertension

Keywords

pulmonary arterial hypertension; bosentan; sildenafil; combination therapy; Compass 3

Outcome Measures

Primary Outcomes (1)

• Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters

  The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period

  at 16 weeks and at 28 weeks of a stepped approach to therapy

Study Arms (1)

Bosentan

EXPERIMENTAL

Oral bosentan 62.5 mg twice daily (BID) first 4 weeks, followed by 24 weeks of 125 mg BID if the 62.5 mg BID dose was well tolerated, with the addition of sildenafil 20 mg thrice daily (TID) in patients who do not reach the 6-MWT distance threshold at Week 16

Drug: Bosentan; Drug: Sildenafil

Interventions

Bosentan DRUG

Oral bosentan 62.5 mg BID first 4 weeks followed by 24 weeks of 125 mg BID if the 62.5 mg BID dose was well tolerated

Bosentan

Sildenafil DRUG

Oral sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16

Bosentan

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 procedures.
• Males or females ≥ 12 years of age (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
• Symptomatic patients with the following types of PAH belonging to World Health Organization (WHO) Pulmonary Hypertension Classification Group I:
• Idiopathic (IPAH)
• Familial (FPAH)
• Associated with PAH (APAH):
• Collagen vascular disease
• Drugs and toxins
• Patients naïve to treatment with advanced PAH therapies (i.e., endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors or prostacyclins) with a right heart catheterization (RHC) showing all of the following:
• Mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg
• Pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mm Hg when PCWP is not accurately obtained
• Pulmonary vascular resistance ≥ 3 Wood units
• MWT distance ≥ 150 meters and \< 360 meters.

You may not qualify if:

• Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
• Pregnant and/or nursing.
• Women of childbearing potential not using a reliable method of contraception.
• Patients with known human immunodeficiency virus (HIV) infection.
• Patients with significant vasoreactivity during right heart catheterization (i.e., a fall in mPAP to \< 40 mm Hg with a decrease of ≥ 10 mm Hg and with a normal cardiac index ≥ 2.5 l/min.m\^2).
• Patients with restrictive lung disease (i.e., total lung capacity (TLC) \< 60% of normal predicted value).
• Patients with obstructive lung disease (i.e., forced expiratory volume/ forced vital capacity (FEV1/FVC) \< 0.5).
• Patients with impaired left ventricular function (LVEF \<50%) or diastolic dysfunction.
• Patients with portal hypertension, cirrhosis, moderate to severe liver impairment (Child-Pugh Class B or C), or liver enzymes (Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) \> 3.0 times the upper limit of normal range.
• Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) sirolimus, everolimus up to 1 week prior to Baseline (Day 1).
• Patients currently receiving or predicted to require treatment, during the course of the study, with nitrates, protease inhibitors, or alpha-blockers.
• Patients with a hemoglobin concentration \< 75 % of the lower limit of the normal range or \< 8.5 g/dL.
• Patients currently receiving or predicted to require treatment with a prostanoid during the course of the study.
• Patients with systolic blood pressure \< 85 mm Hg.
• Patients with body weight \< 40 kg.

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• Benza RL, Raina A, Gupta H, Murali S, Burden A, Zastrow MS, Park MH, Simon MA. Bosentan-based, treat-to-target therapy in patients with pulmonary arterial hypertension: results from the COMPASS-3 study. Pulm Circ. 2018 Jan-Mar;8(1):2045893217741480. doi: 10.1177/2045893217741480. Epub 2017 Oct 24.

  PMID: 29064349 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Bosentan; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract 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; Piperazines; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Rajiv Patni/Medical Officer
• Organization: Actelion Pharmaceuticals, US, Inc.

(650) 624-6900

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2007
• First Posted: February 9, 2007
• Study Start: March 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 4, 2025
• Results First Posted: May 17, 2013

Record last verified: 2025-01