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

NCT00360087 | Terminated Phase 3

• 1 other identifier: AC-052-371
• Study Type: interventional
• Target: 236
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pulmonary Hypertension; Sickle Cell Anemia

Keywords

Treatment Study; Sickle Cell Anemia; 6-Minute Walk; Right Heart Catheterization; Tracleer; Sickle Cell; SCD

Outcome Measures

Primary Outcomes (1)

• Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.

Interventions

Bosentan DRUG

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
• Intra-uterine devices.
• 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.

You may not qualify if:

• All patients (Groups A and B):
• Any major protocol violation in the preceding double-blind ASSET study\*.
• Hemoglobin concentration less than 6.0 g/dL.
• 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:
• Acute liver disease.
• Newly diagnosed cirrhosis or portal hypertension.
• ALT greater than or equal to 3 times ULN and/or albumin greater than 20% below LLN.
• Newly diagnosed psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.

Sponsors & Collaborators

• Actelion: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Related Publications (4)

• 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. doi: 10.1056/NEJMoa035477.

  PMID: 14985486 BACKGROUND

• 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. doi: 10.1182/blood-2002-03-0948. Epub 2002 Oct 3.

  PMID: 12393669 BACKGROUND

• 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. doi: 10.1164/ajrccm.164.11.2104101. No abstract available.

  PMID: 11739128 BACKGROUND

• Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, Naeije R, Sood N, Swerdlow PS, Hildesheim M, Gladwin MT; ASSET study group*. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010 May;149(3):426-35. doi: 10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17.

  PMID: 20175775 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypertension, Pulmonary; Anemia, Sickle Cell

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 2, 2006
• First Posted: August 3, 2006
• Study Start: March 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: December 1, 2007
• Last Updated: February 3, 2025

Record last verified: 2025-01