Defibrillators, Implantable, Ventricular Fibrillation, Ventricular Tachycardia
Conditions
Keywords
Defibrillators, Implantable, Atrial Fibrillation, Ventricular Tachyarrhythmias, Clinical Trial
Brief summary
The Dual Chamber & Atrial Tachyarrhythmias Adverse Events Study (DATAS) was designed to analyze the ability of dual chamber ICDs, to reduce clinically significant adverse events as compared to single chamber ICD in a non selected population with conventional indication of ICD implantation.
Detailed description
Single chamber (SC) implantable cardioverter defibrillators (ICDs) have several limitations that might be relevant during follow up, like atrial pacing requirements, inadequate therapies, sustained atrial tachyarrhythmias and difficulties to achieve an accurate diagnosis of the arrhythmia. Dual chamber (DC) ICDs offer an attractive rationale solution, although controversy remains if the costs and complexity of the implants offer a real clinical advantage. The DATAS is a, prospective, multicentre, randomized, open labelled study, with three arms (two of them cross-over and the third parallels the other two) The primary objective of this trial is to determine whether use of Dual Chamber ICD (DDED-DDDR NASPE/BPEG Defibrillator/Pacemaker Codes) results in a significant decrease in the number of primary end points. The primary end point is a composite comprising four so-denominated Clinically Significant Adverse Events (CSAE): 1. all-cause mortality 2. invasive intervention, hospitalization (\>24 h) or prolongation of hospitalization due to cardiovascular cause 3. inappropriate shocks (two or more episodes with inappropriate shocks) 4. sustained symptomatic atrial tachyarrhythmias that (a) require urgent termination or (b) last more than 48 h leading to therapeutic intervention. Secondary objectives are: 1. Number of each of the components of the CSAE. 2. Arrhythmia related: atrial tachyarrhythmia (AT), frequency and burden, ventricular tachyarrhythmia frequency and burden number of appropriate shocks, number of inappropriate shocks, need for reprogramming, need for medication/Radiofrequency Ablation (RFA) for arrhythmia control, pacemaker syndrome and development of dual chamber pacing indication. 3. Cardiovascular related: New York Health Association (NYHA) functional class, exercise capacity, left ventricular ejection fraction (LVEF), reduction of medication (diuretics.). 4. Quality of life: evaluated by the SF-36, Minnesota living test, with heart failure and Symptom Checklist instruments.
Interventions
DEVICESingle Chamber Implantable Cardioverter Defibrillator
Single chamber ICD implantation: Medtronic GEM, Medtronic Marquis family of SC ICD
DEVICEDual Chamber implantable cardioverter defibrilator
Dual chamber ICD implantation: Jewel AF & GemIII AT as DC ICDs (DC true and SC sim arms)
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Meet the Class I implantation criteria for single chamber implantable cardioverter defibrillator according to the guidelines (ACC/AHA).
Exclusion criteria
* Permanent atrial fibrillation * Patients without structural heart disease * Patient meets implantation criteria for dual-chamber pacing (symptomatic sinus node disease, all 2nd Atrio-Ventricular (AV) block \[except asymptomatic Mobitz I\] and all 3rd degree AV block ). * Patient with previous system implanted (ICD or pacemaker). * Patients with biventricular stimulation or re-synchronization. * Patient has a mechanical right heart valve. * Patient has medical conditions that would preclude the testing required by the protocol, or limit study participation. * Patient is unwilling or unable to cooperate or give written informed consent, or the patient is a minor and legal guardians refuse to give informed consent. * Patient is or will be inaccessible for follow-up at the study center. * Patients who are enrolled or planning to enroll in other clinical trials during the clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CSAE-score Rate(Clinical Significant Adverse Events Score Rate) | 17 months | Main outcome was defined as the CSAE-score during follow-up: CSAE-score rate. We assigned death as the worst outcome during the entire study; and premature cross-over as the main failure of the assigned therapy. So each CSAE was assigned 1 point but (a) death was assigned a score equal to the max number of CSAE in any individual patient in the entire study +1, and (b) premature authorized crossover was given a score equal to the max number of CSAE in any individual patient in that period. Thus, main outcome was defined as the CSAE-score over length of follow-up resulting in a CSAE-score rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Each of the Components of the CSAE | 17 months | The primary endpoint is a composite of 5 pre-determine Clinical Significant Adverse Events (CSAE): (1) all-cause mortality, (2) invasive intervention due to Cardiovascular cause, (3) hospitalization (\>24h) or prolongation of hospitalization due to CV, (4) inappropriate shocks: two or more episodes with inappropriate shocks, (5) sustained symptomatic ATs that (a) require urgent termination or (b) lasted more than 48 h leading to therapeutic intervention. Number of each of the components of CSAE, counts the number of events for each pre-determined level. |
Participant flow
Recruitment details
Patients were eligible if they met a standard Class I indication for a Single Chamber-Implantable Cardioverter Defibrillator (ICD) according to the 1998 ACC/AHA guidelines. Every patient eligible for ICD was screened at each study centre. Follow-up started immediately after randomization.
Pre-assignment details
The Dual chamber true (DC true) and Single chamber simulated (SC sim) arms crossed over after 8 months. All other crossovers were considered 'premature crossovers' and had to be authorized by an independent Adverse Events Advisory Committee. A 1-month wash out period was implemented after programmed crossover.
Participants by arm
| Arm | Count |
|---|---|
| SC True Allocated to Single Chamber ICD (SC true arm) VVEV-VVI (NASPE/BPEG Defibrillator/Pacemaker Codes) | 111 |
| SC Simulated Then DC True Dual chamber ICD initially programmed as Single Chamber ICD (simulated) then DC true programmed as Dual Chamber true (DDED-DDDR) NASPE/BPEG Defibrillator/Pacemaker Codes. | 111 |
| DC True Then SC Sim Dual chamber ICD initially programmed as a DDED-DDDR (DC true arm) then programmed as Single Chamber simulated | 112 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 1st 8 Month | Death | 7 | 8 | 3 |
| 1st 8 Month | Lost to Follow-up | 1 | 2 | 1 |
| 1st 8 Month | Premature cross-over | 0 | 2 | 2 |
| 2nd 8 Months | Death | 3 | 1 | 3 |
| 2nd 8 Months | Lost to Follow-up | 1 | 5 | 2 |
| 2nd 8 Months | Premature cross-over | 1 | 7 | 9 |
| Randomized | Physician Decision | 4 | 2 | 3 |
| Randomized | Protocol Violation | 2 | 1 | 2 |
| Randomized | Withdrawal by Subject | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | SC True | SC Simulated Then DC True | DC True Then SC Sim | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 50 Participants | 59 Participants | 157 Participants |
| Age, Categorical Between 18 and 65 years | 63 Participants | 61 Participants | 53 Participants | 177 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 11 | 66 years STANDARD_DEVIATION 9 | 64 years STANDARD_DEVIATION 10 |
| LVEF | 35 percentage STANDARD_DEVIATION 13 | 39 percentage STANDARD_DEVIATION 14 | 34 percentage STANDARD_DEVIATION 12 | 36 percentage STANDARD_DEVIATION 13 |
| Region of Enrollment Germany | 29 participants | 29 participants | 31 participants | 89 participants |
| Region of Enrollment Israel | 9 participants | 8 participants | 9 participants | 26 participants |
| Region of Enrollment Italy | 21 participants | 21 participants | 19 participants | 61 participants |
| Region of Enrollment Portugal | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment Spain | 43 participants | 44 participants | 44 participants | 131 participants |
| Region of Enrollment United Kingdom | 6 participants | 6 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 20 Participants | 52 Participants |
| Sex: Female, Male Male | 100 Participants | 90 Participants | 92 Participants | 282 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 111 | 8 / 223 | 3 / 223 |
| serious Total, serious adverse events | 50 / 111 | 49 / 223 | 44 / 223 |
Outcome results
Primary
CSAE-score Rate(Clinical Significant Adverse Events Score Rate)
Main outcome was defined as the CSAE-score during follow-up: CSAE-score rate. We assigned death as the worst outcome during the entire study; and premature cross-over as the main failure of the assigned therapy. So each CSAE was assigned 1 point but (a) death was assigned a score equal to the max number of CSAE in any individual patient in the entire study +1, and (b) premature authorized crossover was given a score equal to the max number of CSAE in any individual patient in that period. Thus, main outcome was defined as the CSAE-score over length of follow-up resulting in a CSAE-score rate.
Time frame: 17 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SC True | CSAE-score Rate(Clinical Significant Adverse Events Score Rate) | 0.112 score/month |
| SC Simulated | CSAE-score Rate(Clinical Significant Adverse Events Score Rate) | 0.128 score/month |
| DC True | CSAE-score Rate(Clinical Significant Adverse Events Score Rate) | 0.075 score/month |
Comparison: The assumed effect of the DC treatment was a reduction from 30 to 15% in the proportion of patients who develop a CSAE, as well as a 15% reduction in the mean of CSAE (from 6 to 5.1). The estimated sample size was 200 (DC true) vs. 100 (SC true) patients followed for 8 months, with a two-sided alfa \< 0.05 and a power of 88.8%.~The sample size was set up to 360 patients (120 patients per arm), considering losses in follow-up.p-value: 0.002895% CI: [0.14, 0.67]Wilcoxon (Mann-Whitney)
Secondary
Number of Each of the Components of the CSAE
The primary endpoint is a composite of 5 pre-determine Clinical Significant Adverse Events (CSAE): (1) all-cause mortality, (2) invasive intervention due to Cardiovascular cause, (3) hospitalization (\>24h) or prolongation of hospitalization due to CV, (4) inappropriate shocks: two or more episodes with inappropriate shocks, (5) sustained symptomatic ATs that (a) require urgent termination or (b) lasted more than 48 h leading to therapeutic intervention. Number of each of the components of CSAE, counts the number of events for each pre-determined level.
Time frame: 17 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SC True | Number of Each of the Components of the CSAE | Inappropiate shocks (>2 episodes) | 13 events |
| SC True | Number of Each of the Components of the CSAE | Hospitalizations (>24h) or prolongued CV | 42 events |
| SC True | Number of Each of the Components of the CSAE | Death | 10 events |
| SC True | Number of Each of the Components of the CSAE | Invasive intervention CV | 11 events |
| SC True | Number of Each of the Components of the CSAE | Long Duration AT | 6 events |
| SC Simulated | Number of Each of the Components of the CSAE | Hospitalizations (>24h) or prolongued CV | 51 events |
| SC Simulated | Number of Each of the Components of the CSAE | Death | 11 events |
| SC Simulated | Number of Each of the Components of the CSAE | Invasive intervention CV | 12 events |
| SC Simulated | Number of Each of the Components of the CSAE | Inappropiate shocks (>2 episodes) | 7 events |
| SC Simulated | Number of Each of the Components of the CSAE | Long Duration AT | 3 events |
| DC True | Number of Each of the Components of the CSAE | Long Duration AT | 1 events |
| DC True | Number of Each of the Components of the CSAE | Inappropiate shocks (>2 episodes) | 3 events |
| DC True | Number of Each of the Components of the CSAE | Death | 4 events |
| DC True | Number of Each of the Components of the CSAE | Hospitalizations (>24h) or prolongued CV | 47 events |
| DC True | Number of Each of the Components of the CSAE | Invasive intervention CV | 10 events |