A Study of Patients Having Pulmonary Hypertension Associated With Sickle Cell Disease and Completing an ASSET Study

Pulmonary Hypertension Clinical Trial

— ASSET-3  

Official title:

Long-Term, Open-Label, Multicenter, Extension Study of Bosentan in Patients With Pulmonary Hypertension Associated With Sickle Cell Disease Completing a Double-Blind ASSET Study (AC-052-368 or AC 052-369)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00360087
• Other study ID #: AC-052-371
• Status: Terminated
• Phase: Phase 3
• First received: August 2, 2006
• Last updated: February 11, 2010
• Start date: March 2006
• Est. completion date: December 2007

Study information

• Verified date: February 2010
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of bosentan therapy (in a study known as ASSET) for patients who have high blood pressure in the lungs associated with sickle cell disease. That form of hypertension places people at risk for complications, including shortness of breath, pain, pneumonia, and death. Previous studies have shown that bosentan can be helpful in reducing pulmonary hypertension.

Patients ages 16 and older who have completed the 16-week treatment in the ASSET 1 or ASSET 2 study and who are not pregnant or breastfeeding may be eligible for this study. The research will be conducted in about 25 hospitals in the United States and Europe. Up to 30 participants will be enrolled. The screening visit will involve a physical examination, blood sample of about 3 teaspoons for laboratory tests, and a pregnancy test. Patients' doctors will give them bosentan tablets (62.5 mg each), to take one in the morning and one in the evening. After 1 month, patients will be told whether the dose should be increased to 125 mg tablets to take twice a day. Two weeks after the increase in dose, a blood test will be done to analyze the drug's effects on the liver. After the start of treatment, patients will return for visits every 6 months, when there will be a 6-minute walking test to measure exercise capacity and evaluate shortness of breath. There will be follow-up for patients up to the end of the study and for 28 days after the last dose of bosentan is taken, to collect information about side effects.

Some patients on bosentan have had changes in liver function and red blood cell count. Side effects commonly reported are headache, flushed appearance, inflammation of the throat and nasal passages, and gastrointestinal symptoms. If patients have sudden worsening in breathing in the first few weeks after taking bosentan, they should immediately tell their doctors, because it may be necessary to change the treatment.

Description:

The object of this study is to assess long-term safety, tolerability and efficacy of bosentan in patients with pulmonary hypertension (PH) associated with sickle cell disease (SCD). The study population will include male and female patients with sickle cell disease (SS,S-beta-Thalassemia) who have previously completed the 16-week treatment period of the double-blind study of bosentan (ASSET 1 or ASSET 2). Patients who meet all the inclusion criteria and none of the exclusion criteria will be started on 62.5 mg bid for 4 weeks and then start the maintenance dose of 125 mg bid (or stay on 62.5 mg if their weight is less than 40kg/90lbs). Patients will be divided into two groups. Group A will consist of patients who begin this study within 4 weeks of completing ASSET 1 or ASSET2. Group B will consist of patients who begin this study longer than 4 weeks after completing ASSET I or ASSET 2. Patients will remain on drug until the FDA approves the drug for use in patients with pulmonary hypertension or until the sponsor decides to stop the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 236
• Est. completion date: December 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

• INCLUSION CRITERIA

• Completion of the 16-week treatment period in the double-blind ASSET study

• Women of childbearing potential must have a negative result on their serum pregnancy test and use reliable methods of contraception during study treatment and for 3 months after study treatment termination.

Reliable methods of contraception are:

1. Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.

2. Intra-uterine devices.

3. Oral, injectable, transdermal or implantable contraceptives only in combination with a barrier method.

Hormone-based contraceptives alone, regardless of the route of administration, are not considered to be 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 prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

Signed written informed consent is obtained from the patient or patient's parent/ legal representative prior to initiation of any study-related procedure.

EXCLUSION CRITERIA

All patients (Groups A and B):

1. Any major protocol violation in the preceding double-blind ASSET study*.

2. Hemoglobin concentration less than 6.0 g/dL.

3. Pregnancy or breast-feeding.

• Protocol violations will be reviewed by the monitor during site visits and discussed with the study staff on an ongoing basis and at the patient's completion of the double-blind study.

Group B only:

4. Acute liver disease.

5. Newly diagnosed cirrhosis or portal hypertension.

6. ALT greater than or equal to 3 times ULN and/or albumin greater than 20% below LLN.

7. Newly diagnosed psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Sickle Cell Anemia

Intervention

Drug:
• Bosentan

Locations

Country	Name	City	State
Netherlands	Amsterdam Medical Center	Amsterdam
United Kingdom	Royal Free Hospital	London
United States	National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike	Bethesda	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Boston University School of medicine	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Illinois	Chicago	Illinois
United States	University Hospitals of Ohio	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Colorado	Denver	Colorado
United States	Henry Ford Health Systems	Detroit	Michigan
United States	Wayne State University Hutzel Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas, Houston	Houston	Texas
United States	University of Kansas	Kansas City	Kansas
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Tennessee	Memphis	Tennessee
United States	Columbia University	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	St. Louis University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Actelion	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

References & Publications (3)

Castro O, Hoque M, Brown BD. Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood. 2003 Feb 15;101(4):1257-61. Epub 2002 Oct 3. — View Citation

Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95. — View Citation

Minter KR, Gladwin MT. Pulmonary complications of sickle cell anemia. A need for increased recognition, treatment, and research. Am J Respir Crit Care Med. 2001 Dec 1;164(11):2016-9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.