Eisenmenger ComplexNCT04732650
Real World Difference After Changing Medication From Nonselective to Selective Endothelin Receptor Antagonist in Stable Eisenmenger Syndrome
An observational study of Eisenmenger Complex, run by Samsung Medical Center.
Trial summary
In this study, the investigator will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Eisenmenger Complex
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 4 Feb 2021to 31 Dec 2024
- Phase
- Observational
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Patient who was scheduled to change Ambrisentan from Bosentan (prospective arm) or who already changed to Ambrisentan from Bosentan (retrospective arm) * Presence of cyanosis with < 95 % arterial oxygen saturation (measured by transcutaneous pulse oximetry) or documented during exercise test (6 minute walk distance test or CPT stress test)
- Inclusion Criteria
- Age at least 18 years
- Patient who was scheduled to change Ambrisentan from Bosentan (prospective arm) or who already changed to Ambrisentan from Bosentan (retrospective arm)
- Presence of cyanosis with < 95 % arterial oxygen saturation (measured by transcutaneous pulse oximetry) or documented during exercise test (6 minute walk distance test or CPT stress test)
- Bosentan treatment more than 3months before changing to Ambrisentan and stable medication dosage for 1 month before changing medication
- Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.75 measured at rest or diagnosed by echocardiography with TR Vmax > 3.5m/s and bidirectional or right to left shunt.
- One of the following diagnosis:
- non-corrected large congenital shunting defect at atrial, ventricular or arterial level: Partial anomalous venous return, atrial septal defect, ventricular septal defect, atrioventricular cushion defect, persistent ductus arteriosus, or a combination of these. ii) Surgically corrected shunting defect (diagnoses as above) with significant residual defect iii) Other diagnoses with univentricular physiology/haemodynamics.
- Exclusion Criteria
- pregnancy or lactation
- women of child-bearing age who are sexually active without practicing reliable methods of contraception
- any disease or impairment that, in the opinion of the investigator, excludes a subject from participation
- substance abuse (alcohol, medicines, drugs)
- acute decompensated heart failure within 7 days before the invasive procedure
- significant anemia (Hb < 9.0 g/dl)
- decompensated symptomatic polycythaemia
- significant impairment of hepatic function (Child Pugh class C)
- Significant left ventricular diseases (LV EF < 45%)
- significant valvular diseases other than tricuspid or pulmonary regurgitation ( mitral or aortic valvular impairment more than moderate degree)
- pericardial constriction
- history of stroke, myocardial infarction or life-threatening arrhythmia within 6 months before screening
- bronchopulmonary dysplasia or other chronic severe lung diseases
- history of significant pulmonary embolism (in situ thromboembolism with optimal anticoagulation can be enrolled)
- other relevant diseases (e.g. HIV infection)
- trisomy 21
- Unstable medication, recent changes in dosage regimen
- Other medication with vascular action
About this study
Official title: Real World Difference After Changing Medication From Nonselective to Selective Endothelin Receptor Antagonist in Stable Eisenmenger Syndrome: Observational Study
In this study, the investigator will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.
Read the detailed description
Endothelin receptor antagonist is an established class of targeted therapy for pulmonary arterial hypertension (PAH). Nonselective ERA, Bosentan was the first approved ERA for PAH. Selective ERA, Ambrisentan was also approved for PAH treatment consequently. Although non-selective and selective ERA are both effective in clinical trials, there is no direct comparison for non-selective and selective ERA. Furthermore, approval study for both non-selective and selective ERA did not include the PAH associated with congenital heart disease (PAH-CHD) with significant shunt including Eisenmenger syndrome. Approval study for Ambrisentan;ARIES-1 and ARIES-2 trials also did not include the PAH-CHD In Korea, Bosentan was approved in 2003 and Ambrisentan was approved in 2009 for idiopathic PAH. Bosentan was also approved for PAH-CHD, however, Amrisentan was not because of limited data for PAH-CHD. Therefore, Bosentan was the only ERA covered by public health insurance since 2018 for PAH-CHD. Recently, Amrisentan was also approved for PAH associated with congenital heart disease including Eisenmger syndrome. And, there is a need for changing medication from double pill medication to once-daily dose medication because of patient's compliance.
PAH associated with CHD includes the group with significant shunt vs without shunt (s/p corrected state). When there is a shunt flow, change in pulmonary vascular resistance (PVR) and cardiac output can be a modulator of shunt flow, thus impact of pulmonary vasodilator on hemodynamics can be different from PAH without shunt. However, there is a limited data for changing ERA from non-selective to selective ERA. Our patients population can be interesting study group to understand the clinical response to changing between ERA because they are uniformly treated with non-selective ERA to selective ERA, Bosentan to Ambrisentan.
In this study, the investigators will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.
- Conditions
- Eisenmenger Complex
- Keywords
- pulmonary arterial hypertension, endothelin receptor antagonist, Eisenmenger complex
- Medical subject headings
- Eisenmenger Complex, Pulmonary Arterial Hypertension
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of WHO FC
WHO functional class I, II, III, IV.
Measured: change from baseline to 6 months
Changes in Borg dyspnea scale
scale 0 -10
Measured: change from baseline to 6 months
TAPSE (TTE measure)
mm pericardial effusion(presence, absence), RA size(mm), RV strain(%)
Measured: change from baseline to 6 months
pericardial effusion (TTE measure)
presence, or absence
Measured: change from baseline to 6 months
RA size (TTE measure)
mm
Measured: change from baseline to 6 months
RV strain(TTE measure)
Measured: change from baseline to 6 months
6-minute walk distances (6MWT)
m
Measured: change from baseline to 6 months
blood pressure at rest (SBP and DBP)
mmHg
Measured: change from baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2021
- Study start4 Feb 2021 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Eisenmenger ComplexStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Sung-A Chang, MD, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04732650
- Sponsor's protocol ID
- 2020-09-212
- Status last verified
- Jan 2021
- First submitted
- 10 Dec 2020
- Last updated
- 1 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bever CT Jr, Asofsky R. Augmented IgG anti-acetylcholine receptor response following chronic penicillamine administration. J Neuroimmunol. 1991 Dec;35(1-3):131-7. doi: 10.1016/0165-5728(91)90168-7.
PubMed 1955562Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M; Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) Investigators. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006 Jul 4;114(1):48-54. doi: 10.1161/CIRCULATIONAHA.106.630715. Epub 2006 Jun 26.
PubMed 16801459Gatzoulis MA, Beghetti M, Galie N, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M; BREATHE-5 Investigators. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study. Int J Cardiol. 2008 Jun 23;127(1):27-32. doi: 10.1016/j.ijcard.2007.04.078. Epub 2007 Jul 20.
PubMed 17658633
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real World Difference After Changing Medication From Nonselective to Selective Endothelin Receptor Antagonist in Stable Eisenmenger Syndrome: Observational Study
- ClinicalTrials.gov ID
- NCT04732650
- Acronym / sponsor ID
- 2020-09-212
- Conditions
- Eisenmenger Complex
- Keywords
- pulmonary arterial hypertension, endothelin receptor antagonist, Eisenmenger complex
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 4 Feb 2021 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 1 Feb 2021 (actual)
- 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.
In this study, the investigator will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.
Detailed description
Endothelin receptor antagonist is an established class of targeted therapy for pulmonary arterial hypertension (PAH). Nonselective ERA, Bosentan was the first approved ERA for PAH. Selective ERA, Ambrisentan was also approved for PAH treatment consequently. Although non-selective and selective ERA are both effective in clinical trials, there is no direct comparison for non-selective and selective ERA. Furthermore, approval study for both non-selective and selective ERA did not include the PAH associated with congenital heart disease (PAH-CHD) with significant shunt including Eisenmenger syndrome. Approval study for Ambrisentan;ARIES-1 and ARIES-2 trials also did not include the PAH-CHD In Korea, Bosentan was approved in 2003 and Ambrisentan was approved in 2009 for idiopathic PAH. Bosentan was also approved for PAH-CHD, however, Amrisentan was not because of limited data for PAH-CHD. Therefore, Bosentan was the only ERA covered by public health insurance since 2018 for PAH-CHD. Recently, Amrisentan was also approved for PAH associated with congenital heart disease including Eisenmger syndrome. And, there is a need for changing medication from double pill medication to once-daily dose medication because of patient's compliance.
PAH associated with CHD includes the group with significant shunt vs without shunt (s/p corrected state). When there is a shunt flow, change in pulmonary vascular resistance (PVR) and cardiac output can be a modulator of shunt flow, thus impact of pulmonary vasodilator on hemodynamics can be different from PAH without shunt. However, there is a limited data for changing ERA from non-selective to selective ERA. Our patients population can be interesting study group to understand the clinical response to changing between ERA because they are uniformly treated with non-selective ERA to selective ERA, Bosentan to Ambrisentan.
In this study, the investigators will evaluate the treatment effects and safety, patient compliance of Ambrisentan in Eisenmenger syndrome in PAH patients who have been previously treated with Bosentan.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Patient who was scheduled to change Ambrisentan from Bosentan (prospective arm) or who already changed to Ambrisentan from Bosentan (retrospective arm) * Presence of cyanosis with < 95 % arterial oxygen saturation (measured by transcutaneous pulse oximetry) or documented during exercise test (6 minute walk distance test or CPT stress test)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of WHO FC
Time frame: change from baseline to 6 months
WHO functional class I, II, III, IV.
Changes in Borg dyspnea scale
Time frame: change from baseline to 6 months
scale 0 -10
TAPSE (TTE measure)
Time frame: change from baseline to 6 months
mm pericardial effusion(presence, absence), RA size(mm), RV strain(%)
pericardial effusion (TTE measure)
Time frame: change from baseline to 6 months
presence, or absence
RA size (TTE measure)
Time frame: change from baseline to 6 months
mm
RV strain(TTE measure)
Time frame: change from baseline to 6 months
6-minute walk distances (6MWT)
Time frame: change from baseline to 6 months
m
blood pressure at rest (SBP and DBP)
Time frame: change from baseline to 6 months
mmHg
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2021.
- Background: PubMed 1955562Bever CT Jr, Asofsky R. Augmented IgG anti-acetylcholine receptor response following chronic penicillamine administration. J Neuroimmunol. 1991 Dec;35(1-3):131-7. doi: 10.1016/0165-5728(91)90168-7.
- Background: PubMed 16801459Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M; Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) Investigators. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006 Jul 4;114(1):48-54. doi: 10.1161/CIRCULATIONAHA.106.630715. Epub 2006 Jun 26.
- Background: PubMed 17658633Gatzoulis MA, Beghetti M, Galie N, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M; BREATHE-5 Investigators. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study. Int J Cardiol. 2008 Jun 23;127(1):27-32. doi: 10.1016/j.ijcard.2007.04.078. Epub 2007 Jul 20.
- Individual participant dataSharing planned: No
Related trials for Eisenmenger Complex
Not yet recruitingPhase 2
Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome
Congenital Heart Disease (CHD), Eisenmenger Syndrome
RecruitingPhase 4
A Study of Sotatercept for Patients With Eisenmenger Syndrome or Unrepaired Shunt-Associated Pulmonary Arterial Hypertension Resistant to Vasodilator Therapy
Eisenmenger Syndrome, Pulmonary Arterial Hypertension of Congenital Heart Disease
RecruitingObservational study
COMPERA / COMPERA-KIDS
Pulmonary Arterial Hypertension (PAH), Pulmonary Hypertension (PH)
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?
An observational study of Eisenmenger Complex, run by Samsung Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 1 Feb 2021. 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.
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 of WHO FC (time frame: change from baseline to 6 months). The study lists 8 primary outcomes in all. 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 NCT04732650, which also lists 3 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 1 Feb 2021.