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The Danish Multicenter Randomised Study on AAI Versus DDD Pacing in Sick Sinus Syndrome

Phase 2
Terminated
Conditions
Sick Sinus Syndrome
Interventions
Device: AAIR/DDDR pacemaker
Registration Number
NCT00236158
Lead Sponsor
The DANPACE Investigator Group
Brief 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).

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. 1,900 patients have been randomised.

2. The last randomised patient has been followed for at least 1 year.

3. The mean follow-up for the whole study population is at least 5.5 years.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1415
Inclusion Criteria

General:

A. Undergoing primary pacemaker implantation B. Able to appear for outpatient follow-up C. Age > 18 years

Symptoms:

D. Syncope or E. Dizzy spells or F. Congestive heart failure

Electrocardiographic:

G. 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

Exclusion Criteria

Clinical:

A. 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.

E. Need for other device implantation: ICD (implantable cardioverter defibrillator) or implantable DC converter (for atrial fibrillation).

F. Carotid sinus syndrome (positive carotid sinus massage with pauses >3 seconds).

Electrocardiographic:

G. Atrioventricular block. H. Bundle-branch block (complete RBBB, LBBB, bifascicular bundle-branch block or non-specific intraventricular block with QRS >0.12 seconds).

I. Chronic atrial fibrillation. J. Atrial fibrillation/atrial flutter with QRS pauses >3 seconds during atrial fibrillation.

K. Atrial fibrillation/atrial flutter with QRS frequency <40/minute for 1 minute.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AAIRAAIR/DDDR pacemaker-
DDDRAAIR/DDDR pacemaker-
Primary Outcome Measures
NameTimeMethod
All cause mortality after a mean follow-up of 5.5 year.5,5 years
Secondary Outcome Measures
NameTimeMethod
Cardiovascular death5,5 years
Chronic atrial fibrillation5,5 years
Paroxysmal atrial fibrillation5,5 years
Arterial thromboembolism5,5 years
Congestive heart failure5,5 years
Need for pacemaker re-operations5,5 years
Quality of life5,5 years
Health economics5,5 years

Trial Locations

Locations (1)

Department of Cardiology, Skejby Sygehus, Aarhus University Hospital

🇩🇰

Aarhus, Denmark

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