Pulmonary Arterial HypertensionPhase 4COMPASS 3NCT00433329
Combination Therapy in Pulmonary Arterial Hypertension
A Phase 4 study testing Bosentan and Sildenafil in people with Pulmonary Arterial Hypertension, run by Actelion.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Bosentan and Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Mar 2007to Aug 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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):
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- 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
- 6-MWT distance ≥ 150 meters and < 360 meters.
Who cannot join
- Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
- Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.
- 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).
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- 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.
- Patients who have received any investigational product within 90 days prior to Baseline.
- Patients who previously received any advanced therapy for PAH (e.g., ERAs, PDE-5 inhibitors or prostacyclins).
- Patients with hypersensitivity to sildenafil or any excipients of its formulation.
- Patients with any contraindication to sildenafil treatment (i.e., nitrates).
- Patients with any recent medical condition limiting the ability to comply with the study requirements (i.e., stroke, myocardial infarction).
- Patients with unstable PAH whose disease state would prohibit the completion of study procedures, in the opinion of the investigator.
- Patients unable to complete a MRI scan (e.g., claustrophobia).
- Patients with permanent cardiac pacemakers, automatic internal cardioverter defibrillators (AICD's), neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.
- Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple premature ventricular contractions (PVCs)/premature atrial contractions (PACs).
- Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.
About this study
Official title: COMPASS 3: An Open-label, Multi-Center Study Employing a Targeted 6-Minute Walk Test (6-MWT) Distance Threshold Approach to Guide Bosentan-Based Therapy and to Assess the Utility of Magnetic Resonance Imaging (MRI) on Cardiac Remodeling
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
- Being tested
- Bosentan, Sildenafil
- Keywords
- pulmonary arterial hypertension, bosentan, sildenafil, combination therapy, Compass 3
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
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
SildenafilDrug
Oral sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Bosentan; Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 16 weeks and at 28 weeks of a stepped approach to therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2007 (estimated)
- Study startMar 2007
- Primary completionMay 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00433329
- Sponsor's protocol ID
- AC-052-419
- Acronym
- COMPASS 3
- Status last verified
- Jan 2025
- First submitted
- 7 Feb 2007
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 29064349
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMPASS 3: An Open-label, Multi-Center Study Employing a Targeted 6-Minute Walk Test (6-MWT) Distance Threshold Approach to Guide Bosentan-Based Therapy and to Assess the Utility of Magnetic Resonance Imaging (MRI) on Cardiac Remodeling
- ClinicalTrials.gov ID
- NCT00433329
- Acronym / sponsor ID
- COMPASS 3 / AC-052-419
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- pulmonary arterial hypertension, bosentan, sildenafil, combination therapy, Compass 3
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- May 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 9 Feb 2007 (estimated)
- Results
- Posted 17 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Experimental | Drug: Bosentan, Drug: SildenafilOral 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 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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:
- 6-MWT distance ≥ 150 meters and < 360 meters.
Key exclusion criteria (26 listed)
- Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
- Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.
- Pregnant and/or nursing.
- Women of childbearing potential not using a reliable method of contraception.
- Patients with known human immunodeficiency virus (HIV) infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanOral 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 | Drug | Bosentan |
| SildenafilOral sildenafil 20 mg TID in patients who do not reach the 6-MWT distance threshold at Week 16 | Drug | Bosentan |
Primary outcome
Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters
Time frame: at 16 weeks and at 28 weeks of a stepped approach to therapy
The 6MWT is a non encouraged test, which measures the walking distance covered over a 6 minute period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29064349Benza 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bosentan and Sildenafil in people with Pulmonary Arterial Hypertension, run by Actelion.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Reaching a 6-Minute Walk Test (6MWT) Distance ≥ 380 Meters (time frame: at 16 weeks and at 28 weeks of a stepped approach to therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00433329, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.