DAPA (Defibrillator After Primary Angioplasty) ¡V Randomized Trial.|
|- candidate number||1166|
|- NTR Number||NTR105|
|- Date ISRCTN created||12-sep-2005|
|- date ISRCTN requested||18-aug-2005|
|- Date Registered NTR||2-aug-2005|
|- Secondary IDs||N/A |
|- Public Title||DAPA (Defibrillator After Primary Angioplasty) ¡V Randomized Trial.|
|- Scientific Title||Implantable Defibrillator early after Primary PCI for ST-Elevation Myocardial Infarction.
|- hypothesis||The aim of the study is to demonstrate a survival benefit of ICD in patients with high-risk characteristics after primary angioplasty for acute MI.|
|- Healt Condition(s) or Problem(s) studied||Primary angioplasty|
|- Inclusion criteria||ST-elevation myocardial infarction treated with primary PCI within 30 days and 60 days before randomisation2.At least one of the following criteria: |
1. TIMI flow after primary PCI less than 3 in the infarct related vessel;
2. Left ventricular ejection lower than 30% as measured within 4 days after admission.
|- Exclusion criteria||1. Class I indication for ICD implantation;|
2. Documented previous myocardial infarction with LVEF < 30%;
3. Age < 18 years;
4. Heart failure with New York Heart Association functional class IV;
5. Inotropic medication within 2 weeks before randomisation;
6. Mechanical tricuspid valve;
7. Serious comorbidity such as cancer, with a high likelihood of death during the trial;
8. Advanced cerebrovascular disease;
9. Unwilling or unable to sign the consent form for participation;
10. Females of childbearing age not using medically prescribed contraceptives.
|- mec approval received||yes|
|- multicenter trial||yes|
|- planned startdate ||3-mrt-2004|
|- planned closingdate||31-mrt-2008|
|- Target number of participants||700|
|- Interventions||ICD implantation.|
|- Primary outcome||The primary endpoint of the study is all-cause mortality. |
|- Secondary outcome||Secondary endpoints are the incidence of sudden cardiac death and sustained ventricular tachycardia (VT). Sudden cardiac death is defined as occurring within 1 hour of the onset of symptoms or, if death is not witnessed, during sleep or within 24 hours of last occasion on which the patient was seen in a healthy state.|
|- Trial web site||http://www.diagram-zwolle.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| J. Klijn|
|- CONTACT for SCIENTIFIC QUERIES||MD. PhD. A.R. Ramdat Misier|
|- Sponsor/Initiator ||A.R. Ramdat Misier, MD, PhD|
(Source(s) of Monetary or Material Support)
|- Publications||1. Priori SG, Aliot E, Blomstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001;22:1374-1450.
2. Kagan A, Yano K, Reed DM, Maclean CJ. Predictors of sudden cardiac death among Hawaiian Japanese men. Am J Epidemiol. 1989;130:268-277.
3. Boersma E, Mercado N, Polderman D, Gardien M, Vos J, Simoons ML. Acute myocardial infarction. Lancet 2003;361:847-58.
4. PCAT Collaborators. Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: Six-month follow-up and analysis of individual patient data from randomized trials.
Am Heart J 2003;145:47-57.
5. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitive review of 23 randomised trials. Lancet 2003;361:13-20.
6. Marcus FI, Cobb LA, Edwards JE, et al. Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction. Am J Cardiol 1988;61:8-15.
7. Statters DJ, Malik M, Redwood S, Hnatkova K, Staunton A, Camm AJ. Use of ventricular premature complexes for risk stratification after acute myocardial infarction in the thrombolytic era. Am J Cardiol 1996;77:133-8.
8. Farb A, Tang AL, Burke AP, Sessums L, Liang Y, Virmani R. Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. Circulation 1995;92:1701-9.
9. Zijlstra F, Hoorntje JC, de Boer MJ, et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413-9.
10. Copie X, Hnatkova K, Staunton A, Fei L, Camm AJ, Malik M. Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study. J Am Coll Cardiol 1996;27:270-6.
11. Hohnloser SH, Franck P, Klingenheben T, Zabel M, Just H. Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial. Circulation 1994;90:1747-56.
12. van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation 1998;97:2302-6.
13. Poli A, Fetiveau R, Vandoni P, et al. Integrated analysis of myocardial blush and ST-segment elevation recovery after successful primary angioplasty: Real-time grading of microvascular reperfusion and prediction of early and late recovery of left ventricular function. Circulation 2002;106:313-8.
14. van 't Hof AW, Liem A, de Boer MJ, Zijlstra F. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Zwolle Myocardial infarction Study Group. Lancet 1997;350:615-9.
15. The Antiarrhythymics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhyhmic-drug therapy with implantable defibrillators in patients resuscitated from-near fatal ventricular arrhythmias. N Engl J Med 1997;337:1576-1583.
16. Siebels J, Kuck KH. Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg). Am Heart J 1994;127(4 Pt 2):1139-44
17. Connoly SJ, Gent M, Roberts RS et al. Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297-302.
18. Holmberg M, Holmberg S, Herlitz J, Gardelöf B, for the Swedish Cardiac Arrest Registry. Survival after cardiac arrest outside hospital in Sweden. Resuscitation 1998:36;29-36.
19. Moss AJ, Hall WJ, Cannon DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmias. N Engl J Med 1996;335:1933-40.
20. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley GE. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882-90.
21. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden cardiac death. N Engl J Med 2000;342:1937-45.
22. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83.
23. ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 2002;106:2145-61.
24. Ezekowitz JA, Armstrong PW, McAlister FA. Implantable Cardioverter Defibrillators in Primary and Secondary Prevention: A Systematic Review of Randomized, Controlled Trials. Ann Intern Med. 2003;138:445-452.
25. Buxton AE, Lee KL, Hafley GA et al. Relation of Ejection Fraction and Inducible Ventricular Tachycardia to Mode of Death in Patients With Coronary Artery Disease. Circulation 2002;106:2466-2472.
26. Reynolds MR, Josephson ME. MADIT II (Second Multicenter Automated Defibrillator Implantation Trial ) Debate. Circulation 2003;108:1779-1783.
27. Wilber DJ, Zareba W, Hall WJ, et al. Time dependence of mortality risk and defibrilllator benefit after myocardial infarction. Circulation 2004;109:1082-1084.
28. Ottervanger JP, Van't Hof AW, Reiffers S, et al. Long-term recovery of left ventricular function after primary angioplasty for acute myocardial infarction.Eur Heart J 2001;22:785-902.
29. Scheller B, Hennen B, Hammer B, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol 2003;42:634-41.
|- Brief summary||Background – Sudden cardiac death is a major cause of death after acute myocardial infarction (AMI). Several studies have shown that an Implantable Cardioverter Defibrillator (ICD) is superior to antiarrhythmic drug treatment in patients who survived an arrhythmic cardiac arrest or an episode of life-threatening ventricular tachycardia. Furthermore, ICD as primary prevention therapy has been accepted in patients with coronary artery disease, decreased systolic left ventricular (LV) function and inducible sustained ventricular tachyarrhythmias. Recently, a prospective randomized study showed that defibrillator therapy was beneficial when added to optimal drug treatment in patients with reduced LV function who survived a myocardial infarction (MI). However, it is not known which patients who have mechanical reperfusion as therapy for AMI could have benefit of prophylactic ICD therapy to reduce sudden cardiac death. Furthermore, since LV function improves in the months after MI, particularly after primary PCI, prophylactic ICD implantation based solely on LV function in the post acute phase of MI is probably not a good criterium for ICD implantation within 30 days.
Design – Prospective randomized study to compare ICD plus conventional medical therapy versus conventional medical therapy alone in patients who survived an AMI treated with primary angioplasty. All patients will be treated with optimized drug-therapy including angiotensin-converting enzyme inhibitors, â-blockers, aspirin and lipid-lowering drugs where appropriate. Additional revascularisation procedures are to the discretion of the investigators. After written informed consent has been obtained patients are randomized in a 1:1 ratio to receive either an ICD or conventional medical therapy alone.
A single-chamber ICD will be implanted, preferably, in the left subclavian area and will be tested in the catheterization laboratory under general anesthesia.
Aims – The aim of the study is to demonstrate a survival benefit of ICD in patients with high-risk characteristics after primary angioplasty for acute MI.
Patients – Inclusionafter primary angioplasty for acute MI within 30-60 days with at least one of the following criteria: 1) TIMI flow after PCI less than 3; 2) left ventricular ejection (LVEF) lower than 30% as measured within 4 days after hospital admission. After 18 months LVEF will be measured and all patients in the conventional medical therapy group with LVEF < 30% will be eligible for ICD implantation. Follow-up will be up to 3 years after randomization. Exclusion criteria include patients who are unwilling or unable to sign the consent form for participation and those in who follow-up cannot be obtained (e.g. foreign patients). Also patients in cardiogenic shock will be excluded.
Sample size calculations – Survival estimations are based on data from the GIPS study, a recently reported study from Zwolle assessing Glucose Insulin Potassium in 940 patients with primary angioplasty. One year mortality was in this trial 7.3%. Based on the above mentioned criteria, a total of 169 patients would have been eligible for inclusion (18%). One-year mortality in this group was 22%, with early mortality 10%. It is assumed that ICD therapy will cause a decrease of 1/3 of the ‘late’mortality. After 3 years, ‘late’mortality will be 32% in the controls, compared to 21.3% in the patients with ICD. A total of 538 patients would be required to demonstrate a significant difference with power 0.8 and alpha 0.05. Because cross-over in the control group can dilute the effect, the sample size will be increased with 30%, resulting in a final sample size of 700 patients, with 350 patients in each group.
End points – The primary endpoint of the study is all-cause mortality. Secondary endpoints are the incidence of sudden cardiac death and sustained ventricular tachycardia (VT). Sudden cardiac death is defined as occurring within 1 hour of the onset of symptoms or, if death is not witnessed, during sleep or within 24 hours of last occasion on which the patient was seen in a healthy state.
|- Main changes (audit trail)|
|- RECORD||2-aug-2005 - 13-dec-2006|
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