Pulmonary Arterial HypertensionPhase 2BICYCLENCT01827059
Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
A Phase 2 study testing Bosentan in people with Pulmonary Arterial Hypertension and Congenital Heart Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
SUMMARY Rationale: Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and is associated with a high mortality rate, despite medical intervention. With the availability of effective therapy, early disease detection is an important strategic objective to improve treatment outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension, Congenital Heart Disease
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2013to Jun 2018
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult (>18 years) and mentally competent
- Open or closed septal defect (ASD I/II, VSD, AVSD)
- Open or closed systemic-to-pulmonary shunt (PDA, PAPVC)
- Negative pregnancy test
- Presence of X-PAH
- One of the following criteria, at peak exercise.
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- mPAP > 34 mmHg with CO ≤ 10 l/min
- mPAP > 40 mmHg with CO ≤ 15 l/min
- mPAP > 45 mmHg with CO ≤ 20 l/min
- mPAP > 50 mmHg with CO ≤ 30 l/min
- a PVR (slope pressure/flow plot) of > 3 mmHg/l/min
Who cannot join
- Incapable of giving informed consent
- Pregnancy or lactation (a pregnancy test is offered to every female patient within fertile age)
- Women of child-bearing age who are sexually active without practising reliable methods of contraception. The use of oral contraceptives only, is not considered reliable. Reliable methods include concomitant use of oral contraceptives and condoms ("Double Dutch"), and those methods with a less than 1% chance of pregnancy during typical use20, including intrauterine contraceptives (Copper T, Mirena), Implanon, and sterilization.
- Substance abuse (alcohol, medicines, drugs)
- Subjects who are not able to perform cardiopulmonary exercise testing
- Any cardiac operation < 6 months before inclusion
Show all 22Show fewer
- PAH of any aetiology other than the one specified in the inclusion criteria
- Left ventricular ejection fraction < 30%
- Significant impairment of renal function (GFR < 30 ml/min/1.73m2)
- Moderate to severe liver disease: Child Pugh class B or C
- Raised plasma transaminases level > three times upper normal limit
- Arterial hypotension (systolic blood pressure < 85mmHg)
- Anaemia (Hb < 10g/L, or <6.21 mmol/L)
- Significant valvular disease, other than tricuspid or pulmonary regurgitation
- Chronic lung disease or total lung capacity < 80% predicted value
- History of significant pulmonary embolism
- Other relevant diseases (HIV infection, Hep B/C infection)
- Subjects with known intolerance to bosentan or their constituents
- Prohibited medication: any medication listed below which has not been discontinued at least 30 days prior to inclusion
- Unspecified or other significant medication (glibenclamide or immunosuppression)
- PAH therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostanoids)
- Medication which is not compatible with bosentan or interferes with its metabolism (inhibitors or inducers of CYP2C9, CYP3A4) or medication which may interfere with bosentan treatment according to the investigator
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Centre
Amsterdam, North Holland, 1105AZ
About this study
Official title: A Randomized Placebo Controlled Trial to Analyze Changes in Pulmonary Arterial Pressures at Peak Exercise in Congenital Heart Disease Patients With Exercise-induced Pulmonary Arterial Hypertension Before and After Treatment With Bosentan, Compared to Placebo
SUMMARY Rationale: Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and is associated with a high mortality rate, despite medical intervention. With the availability of effective therapy, early disease detection is an important strategic objective to improve treatment outcomes. Resting echocardiography is currently the recommended screening modality for high-risk population groups. However, it is clear that abnormalities in resting hemodynamics (and symptoms) are late sequelae of the pathobiological processes that begin in the distal pulmonary arteries. Exercise stress may unmask early pulmonary vascular dysfunction, however the definition, clinical significance, and natural history of 'exercise PAH' remain undefined. However, based on clinical experience and literature the prevalence is estimated at ~ 20%.Treatment with endothelin receptor blockers has shown a beneficial influence on the clinical performance in patients with exercise induced PAH due to systemic sclerosis and primary pulmonary hypertension. Whether endothelin receptor blockers decrease pulmonary pressures and improve clinical outcome in patients with exercise induced pulmonary arterial hypertension due to congenital heart disease is unknown.
Objective: Identify congenital heart disease patients with exercise-induced pulmonary arterial hypertension. Analyze changes in pulmonary arterial pressures at peak exercise in patients with exercise induced pulmonary arterial hypertension before and after treatment with bosentan, compared to placebo.
Read more
Study design: Randomized placebo controlled trial with a study period of 26 weeks.
Study population: Adult congenital heart disease patients with exercise induced pulmonary arterial hypertension (n=40) from the Academic Medical Centre, Amsterdam.
Intervention: After randomization one group (n=20) receives a 125 mg tablet of Bosentan twice daily for 6 months. The other group (n=20) receives placebo for 6 months.
Main study parameters/endpoints: To determine wether bosentan (endothelin receptor inhibitor) decreases mean pulmonary arterial pressure at peak exercise in adult congenital heart disease patients with exercise induced pulmonary arterial hypertension. Furthermore the change in cardiopulmonary exercise capacity and right ventricular function will be investigated.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All investigations, blood analysis excepted, are non-invasive and free of risk. The burden for the patients mainly consists of the time that is consumed by the investigations, namely: history taking + physical examination (15 min); Quality-of-Life- score (15 min); laboratory tests (electrolytes, creatinine, urea, albumin and neurohormones, troponin T); 12 lead electrocardiogram (10 min); exercise echocardiography (30 min); cardiovascular exercise testing (30 min).
The trial medication has a potential risk of liver damage, which will be monitored regularly by laboratory testing of liver transaminases.
- Being tested
- Bosentan, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Tracleer
125-mg orange-white, round, biconvex, film-coated tablets
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Active comparator | Tracleer, 125-mg orange-white, round, biconvex, film-coated tablets Receives: Drug: Bosentan |
| Placebo | Placebo comparator | Placebo tablet Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean pulmonary arterial pressure (mPAP) at peak exercise
- measured by means of transthoracic echocardiography at 3 and 6 months followup: mPAP = 0.6 x systolic PAP.
- peak exercise is defined as 80% of maximum calculated heart rate: peak exercise=0.8*(220-age)
Measured: 26 weeks
Secondary outcomes (7)
Cardiopulmonary exercise capacity
- i.e. peak oxygen consumption, VE/VCO2 ratio, O2 pulse
Measured: 26 weeks
Pulmonary hemodynamics
- i.e. systolic pulmonary arterial pressure, pulmonary vascular resistance, pressure-flow relationships during and at peak exercise
Measured: 26 weeks
Right ventricular function
- i.e. TAPSE, TEI index, TDI-S, right ventricular dimensions
Measured: 26 weeks
Laboratory parameters
- i.e. NT-pro BNP, troponin T
Measured: 26 weeks
NYHA functional class
Measured: 26 weeks
Quality of life
- assessed by TAAQOL-CHD, SF-36 and Minnesota CHD-HF questionnaire
Measured: 26 weeks
Demographics
- age, gender, marital status, work, income.
- assessed by demographic questionnaire
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2013 (estimated)
- Study startOct 2013
- Primary completionFeb 2018 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- A.C.J.M. van Riel, MD, Principal investigator, Academic Medical CentreB.J. Bouma, MD, PhD, Principal investigator, Academic Medical CentreB.J.M. Mulder, MD, PhD, Principal investigator, Academic Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01827059
- Sponsor's protocol ID
- NL 42568.018.12
- Acronym
- BICYCLE
- Status last verified
- Aug 2017
- First submitted
- 5 Apr 2013
- Last updated
- 16 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo Controlled Trial to Analyze Changes in Pulmonary Arterial Pressures at Peak Exercise in Congenital Heart Disease Patients With Exercise-induced Pulmonary Arterial Hypertension Before and After Treatment With Bosentan, Compared to Placebo
- ClinicalTrials.gov ID
- NCT01827059
- Acronym / sponsor ID
- BICYCLE / NL 42568.018.12
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Oct 2013
- Primary completion
- Feb 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 9 Apr 2013 (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.
SUMMARY Rationale: Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and is associated with a high mortality rate, despite medical intervention. With the availability of effective therapy, early disease detection is an important strategic objective to improve treatment outcomes. Resting echocardiography is currently the recommended screening modality for high-risk population groups. However, it is clear that abnormalities in resting hemodynamics (and symptoms) are late sequelae of the pathobiological processes that begin in the distal pulmonary arteries. Exercise stress may unmask early pulmonary vascular dysfunction, however the definition, clinical significance, and natural history of 'exercise PAH' remain undefined. However, based on clinical experience and literature the prevalence is estimated at ~ 20%.Treatment with endothelin receptor blockers has shown a beneficial influence on the clinical performance in patients with exercise induced PAH due to systemic sclerosis and primary pulmonary hypertension. Whether endothelin receptor blockers decrease pulmonary pressures and improve clinical outcome in patients with exercise induced pulmonary arterial hypertension due to congenital heart disease is unknown.
Objective: Identify congenital heart disease patients with exercise-induced pulmonary arterial hypertension. Analyze changes in pulmonary arterial pressures at peak exercise in patients with exercise induced pulmonary arterial hypertension before and after treatment with bosentan, compared to placebo.
Study design: Randomized placebo controlled trial with a study period of 26 weeks.
Study population: Adult congenital heart disease patients with exercise induced pulmonary arterial hypertension (n=40) from the Academic Medical Centre, Amsterdam.
Intervention: After randomization one group (n=20) receives a 125 mg tablet of Bosentan twice daily for 6 months. The other group (n=20) receives placebo for 6 months.
Main study parameters/endpoints: To determine wether bosentan (endothelin receptor inhibitor) decreases mean pulmonary arterial pressure at peak exercise in adult congenital heart disease patients with exercise induced pulmonary arterial hypertension. Furthermore the change in cardiopulmonary exercise capacity and right ventricular function will be investigated.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All investigations, blood analysis excepted, are non-invasive and free of risk. The burden for the patients mainly consists of the time that is consumed by the investigations, namely: history taking + physical examination (15 min); Quality-of-Life- score (15 min); laboratory tests (electrolytes, creatinine, urea, albumin and neurohormones, troponin T); 12 lead electrocardiogram (10 min); exercise echocardiography (30 min); cardiovascular exercise testing (30 min).
The trial medication has a potential risk of liver damage, which will be monitored regularly by laboratory testing of liver transaminases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Active comparator | Drug: BosentanTracleer, 125-mg orange-white, round, biconvex, film-coated tablets |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- adult (>18 years) and mentally competent
- Open or closed septal defect (ASD I/II, VSD, AVSD)
- Open or closed systemic-to-pulmonary shunt (PDA, PAPVC)
- Negative pregnancy test
- Presence of X-PAH
Key exclusion criteria (22 listed)
- Incapable of giving informed consent
- Pregnancy or lactation (a pregnancy test is offered to every female patient within fertile age)
- Women of child-bearing age who are sexually active without practising reliable methods of contraception. The use of oral contraceptives only, is not considered reliable. Reliable methods include concomitant use of oral contraceptives and condoms ("Double Dutch"), and those methods with a less than 1% chance of pregnancy during typical use20, including intrauterine contraceptives (Copper T, Mirena), Implanon, and sterilization.
- Substance abuse (alcohol, medicines, drugs)
- Subjects who are not able to perform cardiopulmonary exercise testing
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 |
|---|---|---|
| BosentanAlso: Tracleer125-mg orange-white, round, biconvex, film-coated tablets | Drug | Bosentan |
| Placebo | Drug | Placebo |
Primary outcome
Change in mean pulmonary arterial pressure (mPAP) at peak exercise
Time frame: 26 weeks
* measured by means of transthoracic echocardiography at 3 and 6 months followup: mPAP = 0.6 x systolic PAP. * peak exercise is defined as 80% of maximum calculated heart rate: peak exercise=0.8*(220-age)
7 secondary outcomes
Cardiopulmonary exercise capacity
Time frame: 26 weeks
Pulmonary hemodynamics
Time frame: 26 weeks
Right ventricular function
Time frame: 26 weeks
Laboratory parameters
Time frame: 26 weeks
NYHA functional class
Time frame: 26 weeks
Quality of life
Time frame: 26 weeks
Demographics
Time frame: 26 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2017.
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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.
A.C.J.M. van Riel, MD principal investigator
Academic Medical Centre
B.J. Bouma, MD, PhD principal investigator
Academic Medical Centre
B.J.M. Mulder, MD, PhD principal investigator
Academic Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosentan in people with Pulmonary Arterial Hypertension and Congenital Heart Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 11 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 16 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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 in mean pulmonary arterial pressure (mPAP) at peak exercise (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Aug 2017.