COMPASS-1 / Hemodynamic effects of a single dose of sildenafil in symptomatic patients on bosentan treatment for pulmonary arterial hypertension – A multicenter, open-label, non-comparative, prospective, phase II study - COMPASS-1

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-005066-37-GB
• Date of registration: 13/02/2006
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd.
• Public title: COMPASS-1 / Hemodynamic effects of a single dose of sildenafil in symptomatic patients on bosentan treatment for pulmonary arterial hypertension – A multicenter, open-label, non-comparative, prospective, phase II study - COMPASS-1
• Scientific title: COMPASS-1 / Hemodynamic effects of a single dose of sildenafil in symptomatic patients on bosentan treatment for pulmonary arterial hypertension – A multicenter, open-label, non-comparative, prospective, phase II study - COMPASS-1
• Date of first enrolment: 15/03/2006
• Target sample size: 44
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005066-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) Signed informed consent

2) Men or women >= 18 years of age

3) Symptomatic PAH (WHO functional class II-III) of the following types:
- Idiopathic
- Familial
- Associated with:
Corrected congenital systemic-to-pulmonary shunts
Drugs and toxins

4) PAH diagnosed by right heart catheter within 24 months before enrollment, showing:
- Mean pulmonary arterial pressure (mPAP) >= 25 mmHg
- Pulmonary capillary wedge pressure (PCWP) <= 15 mmHg

5) Documented non-responsiveness to acute vasoreactivity testing done within 24 months before enrollment but before start of bosentan therapy

6) Treated with bosentan 125 mg b.i.d. as monotherapy for PAH for at least 12 weeks before enrollment

7) Patient stable for at least 12 weeks before enrollment

8) Right heart catheterization for 2-3 hours medically acceptable

9) Pulmonary vascular resistance (PVR) at baseline 1 on the day of study performance >= 320 dyn.sec/cm5

10) Women of childbearing potential must have a negative pre-treatment urine pregnancy test and use a reliable method of contraception during bosentan treatment and for at least 3 months after bosentan treatment termination.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Other types of PAH than listed above

2) Epoprostenol treatment planned

3) Suspected pulmonary veno-occlusive disease based on pulmonary edema during a previous vasoreactivity test or on abnormal findings compatible with that diagnosis (septal lines or pulmonary edema at high resolution computer tomography)

4) Systolic blood pressure < 85 mmHg

5) Body weight < 40 kg

6) Hemoglobin <75% of the lower limit of the normal range

7) AST and/or ALT > 3 times the upper limit of normal ranges

8) Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C

9) Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements

10) Conditions that prevent compliance with the protocol or adherence to therapy

11) Pregnancy or breast-feeding

12) Hypersensitivity to bosentan, sildenafil, or any of the excipients of their formulations

13) Use of an investigational drug within 3 months before enrollment

14) Treatment with PAH drugs, including endothelin receptor antagonists other than bosentan, PDE-5 inhibitors incl sildenafil, parenteral treatment (e.g., epoprostenol), other prostanoids, NO, or L-arginine within 3 months before enrollment

15) Treatment with calcineurin inhibitors (e.g., cyclosporine A, tacrolimus, everolimus, sirolimus), fluconazole, ketoconazole, miconazole, amiodarone, ritonavir, glibenclamide (glyburide), alpha-blockers, nitrates, or calcium antagonists within 3 months before enrollment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Symptomatic Pulmonary Arterial Hypertension (WHO functional class II-III) of the following types: - Idiopathic - Familial - Associated with: Corrected congenital systemic-to-pulmonary shunts Drugs and toxins Patients are already on prescribed bosentan therapy for at least 12 weeks.

Intervention(s)

Trade Name: viagra
Product Name: sildenafil
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sildenafil citrate
CAS Number: 171599-83-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: To assess the effect of a single dose of sildenafil 25 mg on

1) total pulmonary resistance (TPR) and on

2) N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in symptomatic stable patients with PAH already treated with bosentan 125 mg b.i.d. for at least 12 weeks.

3) To explore whether previous treatment with bosentan 125 mg b.i.d. for at least 12 weeks promotes vasoreactivity in patients who had been non-responders in a previous acute vasoreactivity test.

Main Objective: To demonstrate that a single dose of sildenafil 25 mg reduces pulmonary vascular resistance (PVR) in symptomatic stable patients with pulmonary arterial hypertension (PAH) already treated with bosentan 125 mg b.i.d. for at least 12 weeks.

Primary end point(s): PVR reduction from baseline 2 to 60 min after sildenafil administration expressed as percent change. This parameter is expected to be normally distributed with an SD of 20%. The reduction to be detected is 10%.

Secondary ID(s)

AC-052-415

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 26/10/2018
• Date Completed: 30/11/2006
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-005066-37/results