Pulmonary HypertensionPhase 3ASSET-3NCT00360087
A Study of Patients Having Pulmonary Hypertension Associated With Sickle Cell Disease and Completing an ASSET Study
A Phase 3 study testing Bosentan in people with Pulmonary Hypertension and Sickle Cell Anemia, run by Actelion.
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Pulmonary Hypertension, Sickle Cell Anemia
- What is being tested?
- Bosentan
- How many people
- 236 participants
- Where
- No sites listed yet
- Study dates
- Mar 2006to Dec 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
About this study
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)
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.
Read the 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.
- Conditions
- Pulmonary Hypertension, Sickle Cell Anemia
- Being tested
- Bosentan
- Keywords
- Treatment Study, Sickle Cell Anemia, 6-Minute Walk, Right Heart Catheterization, Tracleer, Sickle Cell, SCD
- Medical subject headings
- Hypertension, Pulmonary, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2006 (estimated)
- Study startMar 2006
- Primary completionAug 2007
- Study completionDec 2007
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Enrolment
- 236 participants
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360087
- Sponsor's protocol ID
- AC-052-371
- Acronym
- ASSET-3
- Status last verified
- Jan 2025
- First submitted
- 2 Aug 2006
- Last updated
- 3 Feb 2025
- Results posted
- No
Publications
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.
PubMed 14985486Castro 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.
PubMed 12393669Minter 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.
PubMed 11739128Barst 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.
PubMed 20175775
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00360087
- Acronym / sponsor ID
- ASSET-3 / AC-052-371
- Conditions
- Pulmonary Hypertension, Sickle Cell Anemia
- Keywords
- Treatment Study, Sickle Cell Anemia, 6-Minute Walk, Right Heart Catheterization, Tracleer, Sickle Cell, SCD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 236 participants
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 3 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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.
Key exclusion criteria (10 listed)
- Any major protocol violation in the preceding double-blind ASSET study*.
- Hemoglobin concentration less than 6.0 g/dL.
- Pregnancy or breast-feeding.
- Acute liver disease.
- Newly diagnosed cirrhosis or portal hypertension.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bosentan | Drug | – |
Primary outcome
Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.
Results and safety
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Background: PubMed 14985486Gladwin 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.
- Background: PubMed 12393669Castro 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.
- Background: PubMed 11739128Minter 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.
- Derived from this study: PubMed 20175775Barst 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bosentan in people with Pulmonary Hypertension and Sickle Cell Anemia, run by Actelion.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline to all assessed time points in 6MWT, in Borg dyspnea index, and in modified NYHA functional class.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00360087, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.