Atrial Septal DefectNCT03565471
Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension
An observational study of Atrial Septal Defect and Pulmonary Hypertension, run by University of Aarhus at 1 site in Denmark.
Trial summary
The purpose of the study is to compare exercise capacity, cardiac contractility, pulmonary vascular pressures and heart rate variability between patients with an atrial septal defect and healthy controls. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Atrial Septal Defect, Pulmonary Hypertension
- What is being tested?
- Echocardiography, Right side catheterization and Exercise test
- How many people
- 57 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2018to 1 Nov 2019
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: The ASD patients will be identified through the Danish National Patient Registry (DNPR) and enrolled. The controls will be identified from the general population.
Who may be able to join
- 18 years and above.
- Informed consent to participate.
- Patients: Diagnosed with an atrial septal defect. More than 3 years have passed since closure of the atrial septal defect.
- Controls: No history of heart or lung disease.
Who cannot join
- Lung disease.
- Ischemic heart disease.
- Diabetes.
- Hypertension.
- Valve pathology.
- Patients: Concomitant heart disease
- Controls: Usage of prescription drugs interfering with the cardiopulmonary function.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Dept. of Cardiothoracic & Vascular Surgery, Aarhus University Hospital
Aarhus
About this study
The purpose of the study is to compare exercise capacity, cardiac contractility, pulmonary vascular pressures and heart rate variability between patients with an atrial septal defect and healthy controls.
Read the detailed description
- Background Patients born with atrial septal defect (ASD) in the heart, have long been assumed healthy after closure of their defect. However, recent studies show, that despite closure of the ASD the risks of arrhythmia, stroke and pneumonia are increased. It is also shown that ASD patients die earlier than the background population and the cause of death is most often cardiac. The reason for this higher mortality and morbidity is unknown and the scope of this thesis.
- Aim To determine if closed (both surgical and transcatheter) ASD patients have reduced exercise capacity, impaired right and left ventricular function, increased pressure in the pulmonary system, and reduced heart rate variability when compared with healthy controls. The investigators will also examine if method of closure is of importance.
- Hypothesis Primary endpoint: The shunting effect alters the hemodynamic in the ASD heart resulting in lower cardiopulmonary exercise capacity when compared with healthy controls. Secondary endpoints: The shunting effect alters the hemodynamic in the ASD heart when compared with healthy controls resulting in
- Impaired force frequency relationship with a reduction in contractility at optimal heart rate.
- Increased pulmonary arterial pressure.
- Twice as many ASD patients with decreased heart rate variability. Surgical closure is thought to have a higher impact on the ventricular function than catheter closure resulting in
- Lower contractility in the surgically closed patients as compared to the catheter closure as evaluated by force frequency.
- Twice as many surgically closed patients with decreased heart rate variability compared to catheter closed patients.
- Materials and methods 4.1) Power calculation The number of participants needed in the project is calculated based on the exercise capacity test, which is the primary endpoint. The normal exercise test result is 48 ml O2/kg/min with a standard deviation of 7 ml O2/kg/min. With an expected difference between groups and healthy controls of 15% and a power of 85%, the number of patients needed in each group is 18. Possible drop-outs are taken into account and therefore 20 participants will be included in each ASD group, they will each be matched one to one with controls, resulting in a total of 80 project participants. The secondary endpoints are of a more explorative character, why 20 ASD patients in each group is assumed to be sufficient. 4.2) Exercise capacity, force frequency relationship and pulmonary hypertension 4.2.1) The exercise capacity test is conducted on a semi-supine bicycle, while the patients wears a mask measuring the ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate. Patients pedal until maximal exhaustion, which should be obtained after 8-12 minutes. 4.2.2) During exercise testing, the force frequency relationship is examined using echocardiography. 4.2.3) A Swan-Ganz catheter is used to measure right-sided hemodynamic pressures and blood saturation. 4.3) Heart rate variability Electrocardiographic (ECG) activity and heart rate variability will be monitored using a 2-channel Holter monitor. The data will be analyzed with the Pathfinder analysis software.
- Statistical analysis Results for each group will be expressed as means standard deviation or median range or 95% confidence intervals. One way analysis of variance (ANOVA), paired t-tests and regression analyses will be performed. Analyses will be adjusted for age and sex. The issue of multiple testing/multiple comparisons may arise and only relevant comparisons and analyses will be performed.
- Conditions
- Atrial Septal Defect, Pulmonary Hypertension
- Being tested
- Echocardiography, Right side catheterization, Exercise test, Holter monitor
- Keywords
- Atrial Septal Defect, Exercise Capacity, Pulmonary Hypertension, Heart Rate Variability, Congenital Heart Disease
- Medical subject headings
- Heart Septal Defects, Atrial, Hypertension, Pulmonary, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EchocardiographyDiagnostic test
Standard echocardiography.
Right side catheterizationDiagnostic test
Right side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation.
Exercise testDiagnostic test
Exercise test on a supine bicycle with gradual increase in work load while wearing a mask that measures ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate.
Holter monitorDiagnostic test
Holter monitor worn for 2 whole days registering heart rate.
| Study group | Role | What they receive |
|---|---|---|
| ASD patients with surgical closure | Patients diagnosed with an ASD who have had a surgical closure of the defect more than 3 years ago.
Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. Receives: Diagnostic Test: Echocardiography; Diagnostic Test: Right side catheterization; Diagnostic Test: Exercise test; Diagnostic Test: Holter monitor | |
| ASD patients with transcatheter closure | Patients diagnosed with an ASD who have had a transcatheter closure of the defect more than 3 years ago.
Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. Receives: Diagnostic Test: Echocardiography; Diagnostic Test: Right side catheterization; Diagnostic Test: Exercise test; Diagnostic Test: Holter monitor | |
| Controls | Controls who do not have any cardiac or pulmonary diagnoses nor use prescription drugs that may affect the cardiopulmonary function.
Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. Receives: Diagnostic Test: Echocardiography; Diagnostic Test: Right side catheterization; Diagnostic Test: Exercise test; Diagnostic Test: Holter monitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak oxygen uptake (ml O2/kg/min)
using exercise testing
Measured: 8-12 minutes
Peak exercise minute ventilation (ml/min)
using exercise testing
Measured: 8-12 minutes
Peak heart rate (beats/min)
using exercise testing
Measured: 8-12 minutes
Maximal workload (W/kg)
using exercise testing
Measured: 8-12 minutes
Secondary outcomes (10)
Tricuspid annular peak systolic velocity (mm)
using echocardiography
Measured: 8-12 minutes
Return gradient at the tricuspid valve (mmHg)
using echocardiography
Measured: 8-12 minutes
Cardiac output (L/min)
using right sided catheterization
Measured: 8-12 minutes
Cardiac index (L/min)
using right sided catheterization, derived measure adjusted for body surface area
Measured: 8-12 minutes
Central venous pressure (mmHg)
using right sided catheterization
Measured: 8-12 minutes
Pulmonary artery wedge pressure (mmHg)
using right sided catheterization
Measured: 8-12 minutes
Pulmonary artery pressure (mmHg)
using right sided catheterization
Measured: 8-12 minutes
Mixed venous oxygen saturation (%)
using right sided catheterization
Measured: 8-12 minutes
Heart rate variability
using Holter monitoring
Measured: 48 hours
Heart rate, minimum, maximum and mean (beats/min)
using Holter monitoring
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2018
- Study start1 Aug 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial Septal DefectStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Zarmiga Karunanithi, MD, Principal investigator, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03565471
- Sponsor's protocol ID
- 2018-21
- Status last verified
- Jun 2019
- First submitted
- 18 Jun 2018
- Last updated
- 6 May 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Karunanithi Z, Andersen MJ, Mellemkjaer S, Alstrup M, Waziri F, Skibsted Clemmensen T, Elisabeth Hjortdal V, Hvitfeldt Poulsen S. Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study. J Am Heart Assoc. 2021 Jul 20;10(14):e020692. doi: 10.1161/JAHA.120.020692. Epub 2021 Jul 14.
PubMed 34259012Alstrup M, Karunanithi Z, Maagaard MO, Poulsen SH, Hjortdal VE. Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study. Eur J Cardiothorac Surg. 2021 Dec 27;61(1):83-89. doi: 10.1093/ejcts/ezab235.
PubMed 34015096
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atrial Septal Defect - Exercise Capacity and Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT03565471
- Acronym / sponsor ID
- 2018-21
- Conditions
- Atrial Septal Defect, Pulmonary Hypertension
- Keywords
- Atrial Septal Defect, Exercise Capacity, Pulmonary Hypertension, Heart Rate Variability, Congenital Heart Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 21 Jun 2018 (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.
The purpose of the study is to compare exercise capacity, cardiac contractility, pulmonary vascular pressures and heart rate variability between patients with an atrial septal defect and healthy controls.
Detailed description
- Background Patients born with atrial septal defect (ASD) in the heart, have long been assumed healthy after closure of their defect. However, recent studies show, that despite closure of the ASD the risks of arrhythmia, stroke and pneumonia are increased. It is also shown that ASD patients die earlier than the background population and the cause of death is most often cardiac. The reason for this higher mortality and morbidity is unknown and the scope of this thesis.
- Aim To determine if closed (both surgical and transcatheter) ASD patients have reduced exercise capacity, impaired right and left ventricular function, increased pressure in the pulmonary system, and reduced heart rate variability when compared with healthy controls. The investigators will also examine if method of closure is of importance.
- Hypothesis Primary endpoint: The shunting effect alters the hemodynamic in the ASD heart resulting in lower cardiopulmonary exercise capacity when compared with healthy controls. Secondary endpoints: The shunting effect alters the hemodynamic in the ASD heart when compared with healthy controls resulting in
- Impaired force frequency relationship with a reduction in contractility at optimal heart rate.
- Increased pulmonary arterial pressure.
- Twice as many ASD patients with decreased heart rate variability. Surgical closure is thought to have a higher impact on the ventricular function than catheter closure resulting in
- Lower contractility in the surgically closed patients as compared to the catheter closure as evaluated by force frequency.
- Twice as many surgically closed patients with decreased heart rate variability compared to catheter closed patients.
- Materials and methods 4.1) Power calculation The number of participants needed in the project is calculated based on the exercise capacity test, which is the primary endpoint. The normal exercise test result is 48 ml O2/kg/min with a standard deviation of 7 ml O2/kg/min. With an expected difference between groups and healthy controls of 15% and a power of 85%, the number of patients needed in each group is 18. Possible drop-outs are taken into account and therefore 20 participants will be included in each ASD group, they will each be matched one to one with controls, resulting in a total of 80 project participants. The secondary endpoints are of a more explorative character, why 20 ASD patients in each group is assumed to be sufficient. 4.2) Exercise capacity, force frequency relationship and pulmonary hypertension 4.2.1) The exercise capacity test is conducted on a semi-supine bicycle, while the patients wears a mask measuring the ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate. Patients pedal until maximal exhaustion, which should be obtained after 8-12 minutes. 4.2.2) During exercise testing, the force frequency relationship is examined using echocardiography. 4.2.3) A Swan-Ganz catheter is used to measure right-sided hemodynamic pressures and blood saturation. 4.3) Heart rate variability Electrocardiographic (ECG) activity and heart rate variability will be monitored using a 2-channel Holter monitor. The data will be analyzed with the Pathfinder analysis software.
- Statistical analysis Results for each group will be expressed as means standard deviation or median range or 95% confidence intervals. One way analysis of variance (ANOVA), paired t-tests and regression analyses will be performed. Analyses will be adjusted for age and sex. The issue of multiple testing/multiple comparisons may arise and only relevant comparisons and analyses will be performed.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ASD patients with surgical closure | – | Diagnostic Test: Echocardiography, Diagnostic Test: Right side catheterization, Diagnostic Test: Exercise test, Diagnostic Test: Holter monitorPatients diagnosed with an ASD who have had a surgical closure of the defect more than 3 years ago. Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. |
| ASD patients with transcatheter closure | – | Diagnostic Test: Echocardiography, Diagnostic Test: Right side catheterization, Diagnostic Test: Exercise test, Diagnostic Test: Holter monitorPatients diagnosed with an ASD who have had a transcatheter closure of the defect more than 3 years ago. Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. |
| Controls | – | Diagnostic Test: Echocardiography, Diagnostic Test: Right side catheterization, Diagnostic Test: Exercise test, Diagnostic Test: Holter monitorControls who do not have any cardiac or pulmonary diagnoses nor use prescription drugs that may affect the cardiopulmonary function. Echocardiography, right side catheterization, exercise testing and Holter monitoring are performed on all participants. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The ASD patients will be identified through the Danish National Patient Registry (DNPR) and enrolled. The controls will be identified from the general population.
Key inclusion criteria (4 listed)
- 18 years and above.
- Informed consent to participate.
- Patients: Diagnosed with an atrial septal defect. More than 3 years have passed since closure of the atrial septal defect.
- Controls: No history of heart or lung disease.
Key exclusion criteria (7 listed)
- Lung disease.
- Ischemic heart disease.
- Diabetes.
- Hypertension.
- Valve pathology.
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 |
|---|---|---|
| EchocardiographyStandard echocardiography. | Diagnostic test | ASD patients with surgical closure, ASD patients with transcatheter closure, Controls |
| Right side catheterizationRight side catheterization with the purpose of measuring pulmonary vascular pressures and blood saturation. | Diagnostic test | ASD patients with surgical closure, ASD patients with transcatheter closure, Controls |
| Exercise testExercise test on a supine bicycle with gradual increase in work load while wearing a mask that measures ventilation, oxygen uptake, carbon dioxide release and respiratory exchange rate. | Diagnostic test | ASD patients with surgical closure, ASD patients with transcatheter closure, Controls |
| Holter monitorHolter monitor worn for 2 whole days registering heart rate. | Diagnostic test | ASD patients with surgical closure, ASD patients with transcatheter closure, Controls |
Primary outcome
Peak oxygen uptake (ml O2/kg/min)
Time frame: 8-12 minutes
using exercise testing
Peak exercise minute ventilation (ml/min)
Time frame: 8-12 minutes
using exercise testing
Peak heart rate (beats/min)
Time frame: 8-12 minutes
using exercise testing
Maximal workload (W/kg)
Time frame: 8-12 minutes
using exercise testing
10 secondary outcomes
Tricuspid annular peak systolic velocity (mm)
Time frame: 8-12 minutes
Return gradient at the tricuspid valve (mmHg)
Time frame: 8-12 minutes
Cardiac output (L/min)
Time frame: 8-12 minutes
Cardiac index (L/min)
Time frame: 8-12 minutes
Central venous pressure (mmHg)
Time frame: 8-12 minutes
Pulmonary artery wedge pressure (mmHg)
Time frame: 8-12 minutes
Pulmonary artery pressure (mmHg)
Time frame: 8-12 minutes
Mixed venous oxygen saturation (%)
Time frame: 8-12 minutes
Heart rate variability
Time frame: 48 hours
Heart rate, minimum, maximum and mean (beats/min)
Time frame: 48 hours
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 6 May 2021.
- Derived from this study: PubMed 34259012Karunanithi Z, Andersen MJ, Mellemkjaer S, Alstrup M, Waziri F, Skibsted Clemmensen T, Elisabeth Hjortdal V, Hvitfeldt Poulsen S. Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study. J Am Heart Assoc. 2021 Jul 20;10(14):e020692. doi: 10.1161/JAHA.120.020692. Epub 2021 Jul 14.
- Derived from this study: PubMed 34015096Alstrup M, Karunanithi Z, Maagaard MO, Poulsen SH, Hjortdal VE. Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study. Eur J Cardiothorac Surg. 2021 Dec 27;61(1):83-89. doi: 10.1093/ejcts/ezab235.
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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.
Zarmiga Karunanithi, MD principal investigator
University of Aarhus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atrial Septal Defect and Pulmonary Hypertension, run by University of Aarhus at 1 site in Denmark.
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 4 inclusion and 7 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 6 May 2021. 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 Denmark. 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. 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?
Peak oxygen uptake (ml O2/kg/min) (time frame: 8-12 minutes). The study lists 4 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 NCT03565471, which also lists 2 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 6 May 2021.