Sick Sinus SyndromePhase 2/3NCT00236158
The Danish Multicenter Randomised Study on AAI Versus DDD Pacing in Sick Sinus Syndrome
A Phase 2/3 study testing AAIR/DDDR pacemaker in people with Sick Sinus Syndrome, run by The DANPACE Investigator Group at 1 site in Denmark.
Trial summary
Hypothesis Treatment with rate adaptive single chamber atrial pacing (AAIR) reduces the risk of death compared with rate adaptive dual chamber pacing (DDDR) in patients with sick sinus syndrome (SSS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sick Sinus Syndrome
- What is being tested?
- AAIR/DDDR pacemaker
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,415 participants
- Where
- 1 siteDenmark
- Study dates
- Mar 1999to Jul 2010
- Phase
- Phase 2/3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- General:
- Undergoing primary pacemaker implantation B. Able to appear for outpatient follow-up C. Age > 18 years
- Symptoms:
- Syncope or E. Dizzy spells or F. Congestive heart failure
- Electrocardiographic:
- Sinus bradycardia <40/minute for at least 1 minute in a conscious awake state or H. Sinus arrest/sinoatrial block >2 seconds or I. Bradycardia/tachycardia with sinus-pauses >2 seconds
Who cannot join
- Clinical:
- Malignant disease. B. Severe psychogenic disease including severe decrepitude and dementia. C. Impending larger operation expected to influence the major end point. D. Cardiac disorder expected to need cardiac surgery during the follow-up period.
- Need for other device implantation: ICD (implantable cardioverter defibrillator) or implantable DC converter (for atrial fibrillation).
- Carotid sinus syndrome (positive carotid sinus massage with pauses >3 seconds).
- Electrocardiographic:
- Atrioventricular block. H. Bundle-branch block (complete RBBB, LBBB, bifascicular bundle-branch block or non-specific intraventricular block with QRS >0.12 seconds).
- Chronic atrial fibrillation. J. Atrial fibrillation/atrial flutter with QRS pauses >3 seconds during atrial fibrillation.
- Atrial fibrillation/atrial flutter with QRS frequency <40/minute for 1 minute.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Cardiology, Skejby Sygehus, Aarhus University Hospital
Aarhus, DK-8200
About this study
Hypothesis Treatment with rate adaptive single chamber atrial pacing (AAIR) reduces the risk of death compared with rate adaptive dual chamber pacing (DDDR) in patients with sick sinus syndrome (SSS).
Primary purpose The primary purpose of this randomised trial is to compare AAIR and DDDR pacing in patients with SSS and normal atrioventricular (AV) conduction with respect to the primary end point overall mortality.
Read the detailed description
Background In patients with isolated SSS, who need pacemaker treatment, any pacemaker can be used to treat the symptomatic bradycardia: a single chamber atrial (AAI) pacemaker, a single chamber ventricular (VVI) pacemaker, or a dual chamber (DDD) pacemaker. In the USA and in most European countries, DDD pacing is used in most cases. It is now known from the Danish AAI/VVI trial, that AAI pacing is superior to VVI pacing, since VVI pacing is associated with a higher mortality and a higher incidence of atrial fibrillation, thromboembolic complications and heart failure. This confirms previous findings in observational studies. Therefore, VVI pacing should no longer be used in patients with SSS.
The main argument for using DDD pacing is the concern, that the patients will develop symptomatic atrioventricular (AV) block. In the Danish AAI/VVI trial, the risk of AV block was approximately 0.6% per year, which is equivalent to the risk found in a larger meta analysis. This is only a little higher that the risk of atrioventricular block in the age-matched non-paced population. Implantation of a DDD pacemaker in all patients will effectively prevent development of symptomatic bradycardia in the minority of patients who develops AV block. However, the most important disadvantage during DDD pacing is the stimulation (pacing) of the ventricles by the pacemaker a large part of the time, also in patients without AV block. Pacing the right ventricle causes an asynchronous electrical activation and mechanical contraction of the ventricles as compared with the normal physiological contraction.
At present time, a randomised comparison of AAI and DDD pacing in patients with SSS has never been conducted, and to our knowledge, such a trial is not planned anywhere else.
Since several of the patients with SSS suffer from chronotropic incompetence, pacemakers with rate adaptive function are chosen for all patients included in the present trial.
All patients, that fulfils the inclusion criteria and none of the exclusion criteria and who give written informed consent, are included into the study. For all other patients undergoing primary pacemaker implantation in the study period, an exclusion data sheet is filled in stating the reason for exclusion. A total of 1,900 patients are included into the study.
Prior to the pacemaker implantation patients are randomised by lot (envelope) to either AAIR or DDDR pacing. The randomisation is performed after written informed consent has been obtained from the patient. Randomisation will ensure that all centres will randomise an equal number of patients into each treatment group.
Patients randomised to AAIR pacing will have a bipolar lead implanted in their right atrium connected to a single chamber pacemaker with rate adaptive function. Patients randomised to DDDR pacing will have two leads (one bipolar lead in their right atrium and a uni- or bipolar lead in their right ventricle) connected to a DDDR pacemaker.
Out of hospital follow-up The patients must attend for out of hospital follow-up after 3 months and 12 months and then once every year.
Criteria for closing the study
The DANPACE study is stopped and results are analysed when all of the following three criteria are fulfilled:
- 1,900 patients have been randomised.
- The last randomised patient has been followed for at least 1 year.
- The mean follow-up for the whole study population is at least 5.5 years.
- Conditions
- Sick Sinus Syndrome
- Being tested
- AAIR/DDDR pacemaker
- Medical subject headings
- Sick Sinus Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAIR/DDDR pacemakerDevice
Pacemaker with single lead or dual lead
| Study group | Role | What they receive |
|---|---|---|
| AAIR | Other | Not described Receives: Device: AAIR/DDDR pacemaker |
| DDDR | Other | Not described Receives: Device: AAIR/DDDR pacemaker |
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause mortality after a mean follow-up of 5.5 year.
Measured: 5,5 years
Secondary outcomes (8)
Cardiovascular death
Measured: 5,5 years
Chronic atrial fibrillation
Measured: 5,5 years
Paroxysmal atrial fibrillation
Measured: 5,5 years
Arterial thromboembolism
Measured: 5,5 years
Congestive heart failure
Measured: 5,5 years
Need for pacemaker re-operations
Measured: 5,5 years
Quality of life
Measured: 5,5 years
Health economics
Measured: 5,5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2005 (estimated)
- Study startMar 1999
- Primary completionJul 2010 (estimated)
- Study completionJul 2010 (estimated)
Why it stopped: Not able to recruit the estimated number of patients
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 Sick Sinus SyndromeStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,415 participants (actual)
Sponsor and investigators
- Lead sponsor
- The DANPACE Investigator Group
- Sponsor type
- University, hospital or other
- Investigators
- Henning R Andersen, MD, DMSc, Principal investigator, Skejby Sygehus, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00236158
- Sponsor's protocol ID
- 25100
- Other IDs
- NCT00236158
- Status last verified
- Feb 2009
- First submitted
- 10 Oct 2005
- Last updated
- 24 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kirkfeldt RE, Andersen HR, Nielsen JC; DANPACE Investigators. System upgrade and its complications in patients with a single lead atrial pacemaker: data from the DANPACE trial. Europace. 2013 Aug;15(8):1166-73. doi: 10.1093/europace/eut039. Epub 2013 Feb 28.
PubMed 23449923Nielsen JC, Thomsen PE, Hojberg S, Moller M, Riahi S, Dalsgaard D, Mortensen LS, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE investigators. Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing. Europace. 2012 May;14(5):682-9. doi: 10.1093/europace/eur365. Epub 2011 Nov 20.
PubMed 22106360Nielsen JC, Thomsen PE, Hojberg S, Moller M, Vesterlund T, Dalsgaard D, Mortensen LS, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE Investigators. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J. 2011 Mar;32(6):686-96. doi: 10.1093/eurheartj/ehr022. Epub 2011 Feb 7.
PubMed 21300730
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Danish Multicenter Randomised Study on AAI Versus DDD Pacing in Sick Sinus Syndrome
- ClinicalTrials.gov ID
- NCT00236158
- Acronym / sponsor ID
- 25100
- Conditions
- Sick Sinus Syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not able to recruit the estimated number of patients
- Enrolment
- 1,415 participants (actual)
- Lead sponsor
- The DANPACE Investigator GroupUniversity, hospital or other
- Study start
- Mar 1999
- Primary completion
- Jul 2010 (estimated)
- Study completion
- Jul 2010 (estimated)
- First posted
- 12 Oct 2005 (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.
Hypothesis Treatment with rate adaptive single chamber atrial pacing (AAIR) reduces the risk of death compared with rate adaptive dual chamber pacing (DDDR) in patients with sick sinus syndrome (SSS).
Primary purpose The primary purpose of this randomised trial is to compare AAIR and DDDR pacing in patients with SSS and normal atrioventricular (AV) conduction with respect to the primary end point overall mortality.
Detailed description
Background In patients with isolated SSS, who need pacemaker treatment, any pacemaker can be used to treat the symptomatic bradycardia: a single chamber atrial (AAI) pacemaker, a single chamber ventricular (VVI) pacemaker, or a dual chamber (DDD) pacemaker. In the USA and in most European countries, DDD pacing is used in most cases. It is now known from the Danish AAI/VVI trial, that AAI pacing is superior to VVI pacing, since VVI pacing is associated with a higher mortality and a higher incidence of atrial fibrillation, thromboembolic complications and heart failure. This confirms previous findings in observational studies. Therefore, VVI pacing should no longer be used in patients with SSS.
The main argument for using DDD pacing is the concern, that the patients will develop symptomatic atrioventricular (AV) block. In the Danish AAI/VVI trial, the risk of AV block was approximately 0.6% per year, which is equivalent to the risk found in a larger meta analysis. This is only a little higher that the risk of atrioventricular block in the age-matched non-paced population. Implantation of a DDD pacemaker in all patients will effectively prevent development of symptomatic bradycardia in the minority of patients who develops AV block. However, the most important disadvantage during DDD pacing is the stimulation (pacing) of the ventricles by the pacemaker a large part of the time, also in patients without AV block. Pacing the right ventricle causes an asynchronous electrical activation and mechanical contraction of the ventricles as compared with the normal physiological contraction.
At present time, a randomised comparison of AAI and DDD pacing in patients with SSS has never been conducted, and to our knowledge, such a trial is not planned anywhere else.
Since several of the patients with SSS suffer from chronotropic incompetence, pacemakers with rate adaptive function are chosen for all patients included in the present trial.
All patients, that fulfils the inclusion criteria and none of the exclusion criteria and who give written informed consent, are included into the study. For all other patients undergoing primary pacemaker implantation in the study period, an exclusion data sheet is filled in stating the reason for exclusion. A total of 1,900 patients are included into the study.
Prior to the pacemaker implantation patients are randomised by lot (envelope) to either AAIR or DDDR pacing. The randomisation is performed after written informed consent has been obtained from the patient. Randomisation will ensure that all centres will randomise an equal number of patients into each treatment group.
Patients randomised to AAIR pacing will have a bipolar lead implanted in their right atrium connected to a single chamber pacemaker with rate adaptive function. Patients randomised to DDDR pacing will have two leads (one bipolar lead in their right atrium and a uni- or bipolar lead in their right ventricle) connected to a DDDR pacemaker.
Out of hospital follow-up The patients must attend for out of hospital follow-up after 3 months and 12 months and then once every year.
Criteria for closing the study
The DANPACE study is stopped and results are analysed when all of the following three criteria are fulfilled:
- 1,900 patients have been randomised.
- The last randomised patient has been followed for at least 1 year.
- The mean follow-up for the whole study population is at least 5.5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AAIR | Other | Device: AAIR/DDDR pacemaker |
| DDDR | Other | Device: AAIR/DDDR pacemaker |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Undergoing primary pacemaker implantation B. Able to appear for outpatient follow-up C. Age > 18 years
- Syncope or E. Dizzy spells or F. Congestive heart failure
- Sinus bradycardia <40/minute for at least 1 minute in a conscious awake state or H. Sinus arrest/sinoatrial block >2 seconds or I. Bradycardia/tachycardia with sinus-pauses >2 seconds
Key exclusion criteria (8 listed)
- Malignant disease. B. Severe psychogenic disease including severe decrepitude and dementia. C. Impending larger operation expected to influence the major end point. D. Cardiac disorder expected to need cardiac surgery during the follow-up period.
- Need for other device implantation: ICD (implantable cardioverter defibrillator) or implantable DC converter (for atrial fibrillation).
- Carotid sinus syndrome (positive carotid sinus massage with pauses >3 seconds).
- Atrioventricular block. H. Bundle-branch block (complete RBBB, LBBB, bifascicular bundle-branch block or non-specific intraventricular block with QRS >0.12 seconds).
- Chronic atrial fibrillation. J. Atrial fibrillation/atrial flutter with QRS pauses >3 seconds during atrial fibrillation.
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 |
|---|---|---|
| AAIR/DDDR pacemakerPacemaker with single lead or dual lead | Device | AAIR, DDDR |
Primary outcome
All cause mortality after a mean follow-up of 5.5 year.
Time frame: 5,5 years
8 secondary outcomes
Cardiovascular death
Time frame: 5,5 years
Chronic atrial fibrillation
Time frame: 5,5 years
Paroxysmal atrial fibrillation
Time frame: 5,5 years
Arterial thromboembolism
Time frame: 5,5 years
Congestive heart failure
Time frame: 5,5 years
Need for pacemaker re-operations
Time frame: 5,5 years
Quality of life
Time frame: 5,5 years
Health economics
Time frame: 5,5 years
Results and safety
The study was stopped early (reason given: Not able to recruit the estimated number of patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2009.
- Derived from this study: PubMed 23449923Kirkfeldt RE, Andersen HR, Nielsen JC; DANPACE Investigators. System upgrade and its complications in patients with a single lead atrial pacemaker: data from the DANPACE trial. Europace. 2013 Aug;15(8):1166-73. doi: 10.1093/europace/eut039. Epub 2013 Feb 28.
- Derived from this study: PubMed 22106360Nielsen JC, Thomsen PE, Hojberg S, Moller M, Riahi S, Dalsgaard D, Mortensen LS, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE investigators. Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing. Europace. 2012 May;14(5):682-9. doi: 10.1093/europace/eur365. Epub 2011 Nov 20.
- Derived from this study: PubMed 21300730Nielsen JC, Thomsen PE, Hojberg S, Moller M, Vesterlund T, Dalsgaard D, Mortensen LS, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE Investigators. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J. 2011 Mar;32(6):686-96. doi: 10.1093/eurheartj/ehr022. Epub 2011 Feb 7.
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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.
Henning R Andersen, MD, DMSc principal investigator
Skejby Sygehus, Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AAIR/DDDR pacemaker in people with Sick Sinus Syndrome, run by The DANPACE Investigator Group 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 6 inclusion and 8 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 24 Feb 2009. 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.
What does this combined 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.
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: Not able to recruit the estimated number of patients). 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?
All cause mortality after a mean follow-up of 5.5 year. (time frame: 5,5 years). 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 NCT00236158, 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 24 Feb 2009; AzTrials last refreshed its copy on 29 Oct 2026.