SCOBA-PH: Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT01330108
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arm: 1
• Duration (Months): 13
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the safety and tolerance of changing patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: ambrisentan	Phase 4

Detailed Description

The therapy of pulmonary arterial hypertension (PAH) has been revolutionized with the development and subsequent instruction of oral endothelin receptor antagonists (ERA). The first approved ERA, bosentan (Tracleer, Actelion, Inc.) is an effective drug widely used throughout the world in the therapy of PAH. Newer ERA's, with purported advantages over the first approved drug have since been tested and subsequently been approved for the therapy of PAH in the USA and other countries including ambrisentan (Letairis, Gilead Sciences, Inc.). However, there is little data available on the efficacy, safety and tolerability of the elective change from oral bosentan to oral ambrisentan in PAH.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ambrisentan patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension.	Drug: ambrisentan; ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.; Other Names: Letairis

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Not Able to Tolerate Ambrisentan [baseline to 12 weeks]

   If a subject was not able tolerate ambrisentan, subject was returned to use of bosentan and ambrisentan was withdrawn within first 12 weeks of start. A subject was considered to not be able to tolerate ambrisentan if they experienced an adverse event or side effect that was not acceptable to the subject.

Secondary Outcome Measures

1. Mean Change in Distance for a Six Minute Walk at 12 Weeks Post Start of Ambrisentan [baseline to 12 weeks]

   Evaluate the change in exercise tolerance. Measured the distance a subject was capable of walking in 6 minutes at basline compared to the distance at 12 weeks. The distance was measured in meters. A postive result reflects the distance increased at 12 weeks, a negative result reflects how much shorter the distance was.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients followed routinely in the pulmonary vascular disease clinic at the University of Alabama in Birmingham, greater than or equal to 19 years of age.

2. World Health Organization (WHO) PAH Type I

3. WHO class I-IV symptoms (no functional class exclusion).

4. On bosentan, twice a day, with a maximum daily dose of 250mg, on a stable dose for 3 months with no clinical indication to discontinue the drug (i.e., increased liver function studies or other intolerance). Patients may be on other drug therapies for PAH, and also may be on oxygen therapy (intermittent or continuous).

Exclusion Criteria:

1. Known intolerance or allergy to ambrisentan.

2. Prior therapy with ambrisentan.

3. Current therapy with two phosphodiesterase-5 inhibitors.

4. Change in other approved therapy for PAH (including phosphodiesterase-5 inhibitors and prostanoids) within 4 weeks of baseline study visit.

5. Planned addition of prostanoid for clinical reasons within 3 months of baseline study visit.

6. Active participation in another clinical study involving the medical therapy of PAH.

7. Uncontrolled systemic hypertension or angina pectoris

8. Serum creatinine greater than 2.5 at or within 4 weeks of baseline.

9. Serum liver function studies greater than 3 x normal at or within 4 weeks of baseline study visit.

10. In the opinion of the investigator, a change in PAH therapy would present significant risk to the subject.

11. In the opinion of the investigator, the participant is unlikely to survive for 12 weeks after study entry.

12. In the opinion of the investigator, the participant is likely to undergo lung or heart-lung transplantation within 12 weeks of study entry.

13. A woman of childbearing potential who is not using an acceptable form of contraception.

14. Pregnancy.

15. In the opinion of the investigator, a participant who is not capable or willing to follow the study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

• Principal Investigator: Robert C Bourge, MD, Univerisity of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT01330108
• Other Study ID Numbers: SCOBA-PH
• First Posted: Apr 6, 2011
• Last Update Posted: Aug 11, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by University of Alabama at Birmingham: Pulmonary Arterial Hypertension; PAH; WHO Group 1
• Additional relevant MeSH terms: Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Ambrisentan

Study Results

Participant Flow

Arm/Group Title	Ambrisentan
Arm/Group Description	patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension. ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
Period Title: Overall Study
STARTED	32
COMPLETED	28
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Ambrisentan
Arm/Group Description	patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension. ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.6 (12.9)
Sex: Female, Male (Count of Participants)
Female	26 92.9%
Male	2 7.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 17.9%
White	23 82.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Not Able to Tolerate Ambrisentan
Description	If a subject was not able tolerate ambrisentan, subject was returned to use of bosentan and ambrisentan was withdrawn within first 12 weeks of start. A subject was considered to not be able to tolerate ambrisentan if they experienced an adverse event or side effect that was not acceptable to the subject.
Time Frame	baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ambrisentan
Arm/Group Description	patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension. ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
Measure Participants	28
Number [participants]	4 14.3%

2. Secondary Outcome

Title	Mean Change in Distance for a Six Minute Walk at 12 Weeks Post Start of Ambrisentan
Description	Evaluate the change in exercise tolerance. Measured the distance a subject was capable of walking in 6 minutes at basline compared to the distance at 12 weeks. The distance was measured in meters. A postive result reflects the distance increased at 12 weeks, a negative result reflects how much shorter the distance was.
Time Frame	baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ambrisentan
Arm/Group Description	patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension. ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
Measure Participants	28
Mean (Full Range) [meters]	368.71

Adverse Events

Arm/Group Title	Ambrisentan
Arm/Group Description	patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension. ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
All Cause Mortality
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Other (Not Including Serious) Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	14/32 (43.8%)
Cardiac disorders
edema	10/32 (31.3%)	10
lower extremity edema	2/32 (6.3%)	2
Skin and subcutaneous tissue disorders
rash	1/32 (3.1%)	1
rash, not attibuted to drug	1/32 (3.1%)	1

Limitations/Caveats

There is bias in the study due to the fact that subjects have been proven to tolerate the initial drug in the study (bosentan) and adequate time was not allowed for subjects to be able to tolerate ambisentan

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.