Eisenmenger SyndromeNCT02614417
Sleep-disordered Breathing in Eisenmenger Syndrome
An observational study of Eisenmenger Syndrome and Congenital Heart Disease, run by Copenhagen University Hospital, Rigshospitalet.
Trial summary
Sleep-disordered breathing (SDB) is a wellknown comorbidity in cardiovascular disease. Knowledge about SDB in adult congenital heart disease is limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Eisenmenger Syndrome, Congenital Heart Disease, Sleep-disordered Breathing
- What is being tested?
- Polysomnography
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jun 2013to Sep 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with Eisenmenger syndrome
Who may be able to join
- Eisenmenger Syndrome (definition: Pulmonary ≥ systemic vascular resistance with pulmonary-to-systemic shunt and cyanosis (periphery oxygen saturation < 92% at rest and/or < 87% during exercise).
- Stable for ≥ 3 months (no hospitalization, no change of medication, no deterioration).
Who cannot join
- Down's syndrome.
- Iron deficiency (definition: Ferritin < 12 µg/l and/or transferring saturation < 20%).
- Regular phlebotomy.
- Suspicion of risk of non-compliance.
About this study
Sleep-disordered breathing (SDB) is a wellknown comorbidity in cardiovascular disease. Knowledge about SDB in adult congenital heart disease is limited.
Read the detailed description
Congenital heart defects (CHD) occur in approximately 1% of all live births. Around 5% of adults with CHD develop pulmonary arterial hypertension (PAH), with 25-50% of these patients exhibiting the most serious form, Eisenmenger syndrome. Eisenmenger syndrome is caused by a systemic-to-pulmonary shunt, which eventually leads to high pulmonary vascular resistance with right-to-left or bi-directional shunt. Right-to-left shunting reduces the systemic arterial oxygen capacity and consequently causes cyanosis, which may result in hypoxic tissue damage and multi-organ disease.
The natural history of Eisenmenger syndrome (ES) is generally poor compared to the general population with the latest reported actual survival rates of 94%, 74% and 52% at 40, 50 and 60 years of age, respectively. Until recently conventional symptomatic treatment with diuretics, digitalis, antiarrhythmic, anticoagulants, iron supplement, oxygen therapy, and ultimately heart-lung transplantation were the only options. Most patients die from progressive cardiovascular disease and heart failure, sudden heart death or haemoptysis.
However, the introduction of advanced therapy (AT) has improved symptoms and may also have changed to prognosis of these patients. Thus, newer studies have shown beneficial effect of treatment with advanced therapy including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids. These pulmonary vasodilators are now recognized as targeted therapy in Eisenmenger syndrome.
Sleep-disordered breathing (SDB) with predominantly obstructive or central sleep apnoea (OSA/CSA) with Cheyne-Stokes respiration (CSR) is shown to be a common comorbidity in patients with heart failure (HF), as it is present in at least 50 % of these patients. In the general Danish population the estimated prevalence is 3-18% in men and 5-7% in women.
Studies in HF patients also suggest an increased rate of central sleep apnoea (CSA) versus obstructive sleep apnoea (OSA) compared to the general population. SDB may promote the progression of chronic heart failure (HF) and is independently associated with a decreased survival rate.
The standard treatment for patients with OSA is nocturnal continuous positive airway pressure (CPAP) usually delivered with a tight fitting nasal mask. The benefits of CPAP are well established in this group of patients, as opposed to CSA-patients. The largest randomized study demonstrated no effect of nocturnal CPAP in patients with HF and CSA on heart transplant-free survival, but improvements in apnoea frequency, blood oxygenation and left ventricle function. While CPAP and other assisted breathing devices may be used in SDB related to HF, this have no place in the treatment of patients with ES, as any rise in the intra-thoracic pressure and consequently increased PVR and right-to-left shunting will worsen the cyanosis.
The treatment of CSA in HF remains controversial; however aggressive optimization of the medical treatment in congestive heart failure seems to improve the condition.
In these patients, the effect of CPAP, nocturnal oxygen and drugs stimulating the central respiratory drive are less well documented or related to adverse events such as increased risk of arrhythmias.
Though the relationship between HF and SDB is well established, the prevalence and influence of SDB in Eisenmenger syndrome has not previously been examined.
There are many similarities between ES and HF, but several important differences are also present. In congestive heart failure the ventricular insufficiency is related to an increased left side filling pressure followed by pulmonary stasis or oedema, whereas ES patients often have a normal filling pressure and normal systemic vascular resistance, but high pulmonary vascular resistance (PVR) and cyanosis due to the right-left shunt.
The aims of this study are to examine a group of Eisenmenger Syndrome patients to establish the prevalence of SDB in this patient group, to examine the mechanism (CSA or OSA) behind SDB in Eisenmenger syndrome, and to relate the presence of SDB to a higher level of secondary erythrocytosis.
If a role of SDB in ES is demonstrated, further studies will be necessary to demonstrate whether SDB in Eisenmenger syndrome can be altered by advanced therapy.
Hypotheses
- The prevalence of SDB in Eisenmenger syndrome is higher than in the general population.
- SDB in Eisenmenger syndrome is caused by a central rather than obstructive mechanism.
- SDB in Eisenmenger syndrome is related to a more pronounced secondary erythrocytosis than explained by a daytime measurement of oxygen saturation.
- Being tested
- Polysomnography
- Medical subject headings
- Eisenmenger Complex, Heart Defects, Congenital, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PolysomnographyOther
One night polysomnography performed using standard techniques and scored in accordance with American Academy of Sleep Medicine standards. Polysomnography monitors sleep by electroencephalography (F4-A1, C4-M1, O2-M1 F3-M2, C3-M2, O1-A2), electro-myography (submental and tibialis anterior muscles), electro-oculography, nasal flow, respiratory effort, pulse oximetry and transcutaneous carbon dioxide partial pressure.
| Study group | Role | What they receive |
|---|---|---|
| Polysomnography | Patients undergo an one-night in-hospital polysomnography to diagnose sleep-disordered breathing Receives: Other: Polysomnography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnoea-hypopnoea index
Prevalence of sleep-disordered breathing during 1 night polysomnography measured by apnoea-hypopnoea index.
Measured: 1 night on Day 1
Secondary outcomes (1)
Sleep stages
Characterize the sleep architecture during 1 night polysomnography by evaluating the time spend in various sleep stages (N1, N2, N3, REM, measured by EEG)
Measured: 1 night on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2015 (estimated)
- Study startJun 2013
- Primary completionAug 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Eisenmenger SyndromeStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cristel Sørensen, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02614417
- Sponsor's protocol ID
- 2012-01
- Status last verified
- Nov 2015
- First submitted
- 28 Sep 2015
- Last updated
- 25 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep-disordered Breathing in Eisenmenger Syndrome
- ClinicalTrials.gov ID
- NCT02614417
- Acronym / sponsor ID
- 2012-01
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Aug 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 25 Nov 2015 (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.
Sleep-disordered breathing (SDB) is a wellknown comorbidity in cardiovascular disease. Knowledge about SDB in adult congenital heart disease is limited.
Detailed description
Congenital heart defects (CHD) occur in approximately 1% of all live births. Around 5% of adults with CHD develop pulmonary arterial hypertension (PAH), with 25-50% of these patients exhibiting the most serious form, Eisenmenger syndrome. Eisenmenger syndrome is caused by a systemic-to-pulmonary shunt, which eventually leads to high pulmonary vascular resistance with right-to-left or bi-directional shunt. Right-to-left shunting reduces the systemic arterial oxygen capacity and consequently causes cyanosis, which may result in hypoxic tissue damage and multi-organ disease.
The natural history of Eisenmenger syndrome (ES) is generally poor compared to the general population with the latest reported actual survival rates of 94%, 74% and 52% at 40, 50 and 60 years of age, respectively. Until recently conventional symptomatic treatment with diuretics, digitalis, antiarrhythmic, anticoagulants, iron supplement, oxygen therapy, and ultimately heart-lung transplantation were the only options. Most patients die from progressive cardiovascular disease and heart failure, sudden heart death or haemoptysis.
However, the introduction of advanced therapy (AT) has improved symptoms and may also have changed to prognosis of these patients. Thus, newer studies have shown beneficial effect of treatment with advanced therapy including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids. These pulmonary vasodilators are now recognized as targeted therapy in Eisenmenger syndrome.
Sleep-disordered breathing (SDB) with predominantly obstructive or central sleep apnoea (OSA/CSA) with Cheyne-Stokes respiration (CSR) is shown to be a common comorbidity in patients with heart failure (HF), as it is present in at least 50 % of these patients. In the general Danish population the estimated prevalence is 3-18% in men and 5-7% in women.
Studies in HF patients also suggest an increased rate of central sleep apnoea (CSA) versus obstructive sleep apnoea (OSA) compared to the general population. SDB may promote the progression of chronic heart failure (HF) and is independently associated with a decreased survival rate.
The standard treatment for patients with OSA is nocturnal continuous positive airway pressure (CPAP) usually delivered with a tight fitting nasal mask. The benefits of CPAP are well established in this group of patients, as opposed to CSA-patients. The largest randomized study demonstrated no effect of nocturnal CPAP in patients with HF and CSA on heart transplant-free survival, but improvements in apnoea frequency, blood oxygenation and left ventricle function. While CPAP and other assisted breathing devices may be used in SDB related to HF, this have no place in the treatment of patients with ES, as any rise in the intra-thoracic pressure and consequently increased PVR and right-to-left shunting will worsen the cyanosis.
The treatment of CSA in HF remains controversial; however aggressive optimization of the medical treatment in congestive heart failure seems to improve the condition.
In these patients, the effect of CPAP, nocturnal oxygen and drugs stimulating the central respiratory drive are less well documented or related to adverse events such as increased risk of arrhythmias.
Though the relationship between HF and SDB is well established, the prevalence and influence of SDB in Eisenmenger syndrome has not previously been examined.
There are many similarities between ES and HF, but several important differences are also present. In congestive heart failure the ventricular insufficiency is related to an increased left side filling pressure followed by pulmonary stasis or oedema, whereas ES patients often have a normal filling pressure and normal systemic vascular resistance, but high pulmonary vascular resistance (PVR) and cyanosis due to the right-left shunt.
The aims of this study are to examine a group of Eisenmenger Syndrome patients to establish the prevalence of SDB in this patient group, to examine the mechanism (CSA or OSA) behind SDB in Eisenmenger syndrome, and to relate the presence of SDB to a higher level of secondary erythrocytosis.
If a role of SDB in ES is demonstrated, further studies will be necessary to demonstrate whether SDB in Eisenmenger syndrome can be altered by advanced therapy.
Hypotheses
- The prevalence of SDB in Eisenmenger syndrome is higher than in the general population.
- SDB in Eisenmenger syndrome is caused by a central rather than obstructive mechanism.
- SDB in Eisenmenger syndrome is related to a more pronounced secondary erythrocytosis than explained by a daytime measurement of oxygen saturation.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Polysomnography | – | Other: PolysomnographyPatients undergo an one-night in-hospital polysomnography to diagnose sleep-disordered breathing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Eisenmenger syndrome
Key inclusion criteria (2 listed)
- Eisenmenger Syndrome (definition: Pulmonary ≥ systemic vascular resistance with pulmonary-to-systemic shunt and cyanosis (periphery oxygen saturation < 92% at rest and/or < 87% during exercise).
- Stable for ≥ 3 months (no hospitalization, no change of medication, no deterioration).
Key exclusion criteria (4 listed)
- Down's syndrome.
- Iron deficiency (definition: Ferritin < 12 µg/l and/or transferring saturation < 20%).
- Regular phlebotomy.
- Suspicion of risk of non-compliance.
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 |
|---|---|---|
| PolysomnographyOne night polysomnography performed using standard techniques and scored in accordance with American Academy of Sleep Medicine standards. Polysomnography monitors sleep by electroencephalography (F4-A1, C4-M1, O2-M1 F3-M2, C3-M2, O1-A2), electro-myography (submental and tibialis anterior muscles), electro-oculography, nasal flow, respiratory effort, pulse oximetry and transcutaneous carbon dioxide partial pressure. | Other | Polysomnography |
Primary outcome
Apnoea-hypopnoea index
Time frame: 1 night on Day 1
Prevalence of sleep-disordered breathing during 1 night polysomnography measured by apnoea-hypopnoea index.
1 secondary outcome
Sleep stages
Time frame: 1 night on Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2015.
Related trials for Eisenmenger Syndrome
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 Syndrome and Congenital Heart Disease, run by Copenhagen University Hospital, Rigshospitalet.
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 2 inclusion and 4 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: finished, as of the sponsor's last update on 25 Nov 2015. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Apnoea-hypopnoea index (time frame: 1 night on Day 1). 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 25 Nov 2015.