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A Study of Patients Having Pulmonary Hypertension Associated With Sickle Cell Disease and Completing an ASSET Study (ASSET-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00360087
Recruitment Status : Terminated (Slow enrollment)
First Posted : August 3, 2006
Last Update Posted : February 12, 2010
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:

Brief 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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Sickle Cell Anemia Drug: Bosentan Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 236 participants
Primary Purpose: Treatment
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)
Study Start Date : March 2006
Actual Primary Completion Date : August 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan

Primary Outcome Measures :
  1. Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00360087

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Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sponsor, Actelion Identifier: NCT00360087    
Other Study ID Numbers: AC-052-371
First Posted: August 3, 2006    Key Record Dates
Last Update Posted: February 12, 2010
Last Verified: February 2010
Keywords provided by Actelion:
Treatment Study
Sickle Cell Anemia
6-Minute Walk
Right Heart Catheterization
Sickle Cell
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Anemia, Sickle Cell
Vascular Diseases
Cardiovascular Diseases
Hematologic Diseases
Lung Diseases
Respiratory Tract Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Genetic Diseases, Inborn
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action