Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in Europe

Coronary Artery Disease Clinical Trial

— EU-CERT-ICD  

Official title:

Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in Europe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02064192
• Other study ID #: EU 602299
• Status: Completed
• Start date: May 2014
• Est. completion date: November 2019

Study information

• Verified date: March 2020
• Source: University Medical Center Goettingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The "EUropean Comparative Effectiveness Research to assess the use of primary prophylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD)" is a modular research project to study the effectiveness of prophylactic ICDs in a prospective study, a retrospective registry, and meta-analyses of existing evidence on the subject.

Description:

The prospective study part is an observational, prospective multi-centre study which aims to enrol 2500 patients with ischemic or dilated cardiomyopathy and primary prophylactic ICD indication for reduced left ventricular ejection fraction (LVEF) according to current guidelines. According to the treating physician's decision and preference which is independent from study participation, patients are recruited into one of two groups: patients directly prior to first ICD implantation (ICD Group), or patients who are not considered for prophylactic ICD treatment by the physician or are considered but refuse ICD treatment (Control Group). Patients will undergo simple 12-lead electrocardiogram (ECG) and Holter ECG diagnostics at baseline as well as genetic biobanking at entry to the study. All patients will be subsequently followed for at least 1 year and up to 4 years. Co-primary endpoints are all-cause mortality and appropriate ICD shocks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2285
• Est. completion date: November 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ischemic or dilated cardiomyopathy and recommendation for primary prophylactic ICD treatment following current international treatment guidelines

• Written informed consent

• If ICD implantation is planned, enrollment and study baseline testing needs to be completed before de-novo ICD implantation

Exclusion Criteria:

• Permanent atrial fibrillation or atrial fibrillation at baseline in case more than 15% of such patients at a given time have been enrolled

• Indication for secondary prophylactic ICD treatment

• Indication or candidate for cardiac resynchronization therapy

• AV block II°-III° at resting heart rates

• Implanted pacemaker

• Unstable cardiac disease such as decompensated heart failure (NYHA functional class IV) or acute coronary syndrome

• Participation in other clinical trials which exclude enrolment in other trials

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Coronary Artery Disease
• Dilated Cardiomyopathy
• Implantable Defibrillator User
• Infarction
• Myocardial Infarction

Locations

Country	Name	City	State
Belgium	KU Leuven, Div. of Cardiology	Leuven
Bulgaria	Acibadem City Clinic Tokuda Hospital, Div. of Cardiology	Sofia
Bulgaria	National Heart Hospital, Dept. of Cardiology	Sofia
Bulgaria	St. Anna University Hospital for Active Treatment, Div. of Cardiology	Sofia
Bulgaria	St. Ekaterina Hospital, Div. of Cardiology	Sofia
Croatia	Magdalena Clinic	Krapinske Toplice
Croatia	Klinicki bolnicki centar Rijeka, Div. of Cardiology	Rijeka
Croatia	Klinicki bolnicki centar Split, Div. of Cardiology	Split
Croatia	Opca Bolnica Zadar, Div. of Cardiology	Zadar
Croatia	Klinicki bolnicki centar Sestre milosrdnice, Div. of Cardiology	Zagreb
Czechia	Masaryk University Hospital Brno, Div. of Cardiology	Brno
Czechia	Palacky University Hospital Olomouc, Div. of Cardiology	Olomouc
Denmark	Rigshospitalet, Div. of Cardiology	Copenhagen
Denmark	Gentofte Hospital, Div. of Cardiology	Hellerup
Finland	Department of Internal Medicine, University of Oulu	Oulu
Germany	Charitè Virchow Klinikum (CVK), Div. of Cardiology	Berlin
Germany	CharitéCentrum 1 Health and Human Sciences, Institute for Social Medicine, Epidemiology and Health Economics	Berlin
Germany	Vivantes Humboldt Klinikum, Div. of Cardiology	Berlin
Germany	St. Marien-Hospital, Div. of Cardiology	Bonn
Germany	Klinikum Reinkenheide, Div. of Cardiology	Bremerhaven
Germany	University Medical Center, Div. of Cardiology	Göttingen
Germany	Asklepios Klinikum Barmbek, Div. of Cardiology	Hamburg
Germany	Herz im Zentrum	Hannover
Germany	Klinikum Ludwigsburg, Div. of Cardiology	Ludwigsburg
Germany	Department of Cardiovascular Diseases, German Heart Centre Munich, Technische Universität München	Munich
Germany	Ludwig-Maximilians-University, Div. of Cardiology	Munich
Germany	University Hospital Regensburg, Div. of Cardiology	Regensburg
Germany	University Hospital Tuebingen, Div. of Cardiology	Tuebingen
Germany	Klinikum Weiden, Div. of Cardiology	Weiden
Greece	Attikon University Hospital, Div. of Cardiology	Athens
Hungary	Semmelweis University Heart and Vascular Center	Budapest
Netherlands	Universitair Medisch Centrum Utrecht, Dept. of Physiology & Cardiology	Utrecht
Poland	Medical University of Lodz	Lodz
Poland	Heliodor Swiecicki University Hospital, Div. of Cardiology	Poznan
Poland	Cardinal Stefan Wyszynski Institute of Cardiology (IKARD)	Warszawa
Slovakia	Stredoslovensky´ ústav srdcovy´ch a cievnych chorôb (SUSSCH)	Banska Bystrica
Slovakia	Slovak Medical University, Heart Center	Bratislava
Spain	Hospital Clínic, Universitat de Barcelona	Barcelona
Sweden	Skane University Hospital, Div. of Cardiology	Lund
Sweden	Karolinska Institute, Div. of Cardiology	Stockholm
Switzerland	University Hospital Basel, Div. of Cardiology	Basel
United Kingdom	St. Paul's Cardiac Electrophysiology	London	Purley, Surrey

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Goettingen

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Croatia,  Czechia,  Denmark,  Finland,  Germany,  Greece,  Hungary,  Netherlands,  Poland,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (18)

Al-Khatib SM, Hellkamp A, Bardy GH, Hammill S, Hall WJ, Mark DB, Anstrom KJ, Curtis J, Al-Khalidi H, Curtis LH, Heidenreich P, Peterson ED, Sanders G, Clapp-Channing N, Lee KL, Moss AJ. Survival of patients receiving a primary prevention implantable cardioverter-defibrillator in clinical practice vs clinical trials. JAMA. 2013 Jan 2;309(1):55-62. doi: 10.1001/jama.2012.157182. — View Citation

Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH; Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37. Erratum in: N Engl J Med. 2005 May 19;352(20):2146. — View Citation

Bauer A, Kantelhardt JW, Barthel P, Schneider R, Mäkikallio T, Ulm K, Hnatkova K, Schömig A, Huikuri H, Bunde A, Malik M, Schmidt G. Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet. 2006 May 20;367(9523):1674-81. — View Citation

Buxton AE. Implantable cardioverter-defibrillators for primary prevention of sudden death: the quest to identify patients most likely to benefit. J Am Coll Cardiol. 2012 Oct 23;60(17):1656-8. doi: 10.1016/j.jacc.2012.06.041. Epub 2012 Sep 26. — View Citation

Cowie MR, Marshall D, Drummond M, Ferko N, Maschio M, Ekman M, de Roy L, Heidbuchel H, Verboven Y, Braunschweig F, Linde C, Boriani G. Lifetime cost-effectiveness of prophylactic implantation of a cardioverter defibrillator in patients with reduced left ventricular systolic function: results of Markov modelling in a European population. Europace. 2009 Jun;11(6):716-26. doi: 10.1093/europace/eup068. Epub 2009 Apr 9. — View Citation

Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, Arking DE, Müller-Nurasyid M, Krijthe BP, Lubitz SA, Bis JC, Chung MK, Dörr M, Ozaki K, Roberts JD, Smith JG, Pfeufer A, Sinner MF, Lohman K, Ding J, Smith NL, Smith JD, Rienstra M, Rice KM, Van Wagoner DR, Magnani JW, Wakili R, Clauss S, Rotter JI, Steinbeck G, Launer LJ, Davies RW, Borkovich M, Harris TB, Lin H, Völker U, Völzke H, Milan DJ, Hofman A, Boerwinkle E, Chen LY, Soliman EZ, Voight BF, Li G, Chakravarti A, Kubo M, Tedrow UB, Rose LM, Ridker PM, Conen D, Tsunoda T, Furukawa T, Sotoodehnia N, Xu S, Kamatani N, Levy D, Nakamura Y, Parvez B, Mahida S, Furie KL, Rosand J, Muhammad R, Psaty BM, Meitinger T, Perz S, Wichmann HE, Witteman JC, Kao WH, Kathiresan S, Roden DM, Uitterlinden AG, Rivadeneira F, McKnight B, Sjögren M, Newman AB, Liu Y, Gollob MH, Melander O, Tanaka T, Stricker BH, Felix SB, Alonso A, Darbar D, Barnard J, Chasman DI, Heckbert SR, Benjamin EJ, Gudnason V, Kääb S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012 Apr 29;44(6):670-5. doi: 10.1038/ng.2261. — View Citation

Exner DV, Kavanagh KM, Slawnych MP, Mitchell LB, Ramadan D, Aggarwal SG, Noullett C, Van Schaik A, Mitchell RT, Shibata MA, Gulamhussein S, McMeekin J, Tymchak W, Schnell G, Gillis AM, Sheldon RS, Fick GH, Duff HJ; REFINE Investigators. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol. 2007 Dec 11;50(24):2275-84. Epub 2007 Nov 26. — View Citation

Hlatky MA, Douglas PS, Cook NL, Wells B, Benjamin EJ, Dickersin K, Goff DC, Hirsch AT, Hylek EM, Peterson ED, Roger VL, Selby JV, Udelson JE, Lauer MS. Future directions for cardiovascular disease comparative effectiveness research: report of a workshop sponsored by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2012 Aug 14;60(7):569-80. doi: 10.1016/j.jacc.2011.12.057. Epub 2012 Jul 11. — View Citation

Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001 Nov 15;345(20):1473-82. Review. — View Citation

Koller MT, Schaer B, Wolbers M, Sticherling C, Bucher HC, Osswald S. Death without prior appropriate implantable cardioverter-defibrillator therapy: a competing risk study. Circulation. 2008 Apr 15;117(15):1918-26. doi: 10.1161/CIRCULATIONAHA.107.742155. Epub 2008 Apr 7. — View Citation

Kramer DB, Friedman PA, Kallinen LM, Morrison TB, Crusan DJ, Hodge DO, Reynolds MR, Hauser RG. Development and validation of a risk score to predict early mortality in recipients of implantable cardioverter-defibrillators. Heart Rhythm. 2012 Jan;9(1):42-6. doi: 10.1016/j.hrthm.2011.08.031. Epub 2011 Sep 3. — View Citation

MacFadden DR, Crystal E, Krahn AD, Mangat I, Healey JS, Dorian P, Birnie D, Simpson CS, Khaykin Y, Pinter A, Nanthakumar K, Calzavara AJ, Austin PC, Tu JV, Lee DS. Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. Ann Intern Med. 2012 Feb 7;156(3):195-203. doi: 10.7326/0003-4819-156-3-201202070-00007. — View Citation

Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, Estes NA 3rd, Greenberg H, Hall WJ, Huang DT, Kautzner J, Klein H, McNitt S, Olshansky B, Shoda M, Wilber D, Zareba W; MADIT-RIT Trial Investigators. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012 Dec 13;367(24):2275-83. doi: 10.1056/NEJMoa1211107. Epub 2012 Nov 6. — View Citation

Schmidt G, Malik M, Barthel P, Schneider R, Ulm K, Rolnitzky L, Camm AJ, Bigger JT Jr, Schömig A. Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet. 1999 Apr 24;353(9162):1390-6. — View Citation

Seegers J, Vos MA, Flevari P, Willems R, Sohns C, Vollmann D, Lüthje L, Kremastinos DT, Floré V, Meine M, Tuinenburg A, Myles RC, Simon D, Brockmöller J, Friede T, Hasenfuß G, Lehnart SE, Zabel M; EUTrigTreat Clinical Study Investigators. Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype. Europace. 2012 Mar;14(3):416-22. doi: 10.1093/europace/eur352. Epub 2011 Nov 23. — View Citation

Thomsen MB, Volders PG, Beekman JD, Matz J, Vos MA. Beat-to-Beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced torsades de pointes. J Am Coll Cardiol. 2006 Sep 19;48(6):1268-76. Epub 2006 Aug 28. — View Citation

Tung R, Zimetbaum P, Josephson ME. A critical appraisal of implantable cardioverter-defibrillator therapy for the prevention of sudden cardiac death. J Am Coll Cardiol. 2008 Sep 30;52(14):1111-21. doi: 10.1016/j.jacc.2008.05.058. Review. — View Citation

Zabel M, Malik M, Hnatkova K, Papademetriou V, Pittaras A, Fletcher RD, Franz MR. Analysis of T-wave morphology from the 12-lead electrocardiogram for prediction of long-term prognosis in male US veterans. Circulation. 2002 Mar 5;105(9):1066-70. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-Cause Mortality	Co-Primary Endpoint	one to five years
Primary	First Appropriate ICD Shock	Co-Primary Endpoint	one to five years
Secondary	Time to First Inappropriate Shock		one to five years
Secondary	Sudden Cardiac Death		one to five years
Secondary	Cardiac Death		one to five years
Secondary	Non-Cardiac Death		one to five years
Secondary	Arrhythmogenic Syncope	presumed arrhythmogenic syncopes (per the judgment of each investigator and the endpoint committee)	one to five years
Secondary	Resuscitation	successful resuscitation for ventricular tachyarrhythmias (especially in the non ICD Control Group)	one to five years
Secondary	Any ICD Shock	any ICD shock (appropriate or inappropriate)	one to five years
Secondary	Atrial Fibrillation	atrial fibrillation (if documented), defined as an atrial tachyarrhythmia >250 beats per minute (bpm) lasting at least 30 seconds is considered as secondary endpoint	one to five years
Secondary	Quality of Life	Quality of life (QoL) will be assessed using the questionnaires SF 36, MacNew and Florida Patient Acceptance Survey	one to five years
Secondary	Device Revision / Device Replacement	the secondary endpoint Device Revision/Replacement will be recorded as electrode dislocation/revision, device revision for pocket hematoma, perforation, or infection, device exchange due to malfunction, battery exhaustion, other reason, or upgrade to dual chamber or CRT-D	one to five years
Secondary	Costs and Cost-Effectiveness	the secondary endpoint "Costs" will be assessed using patient questionnaires to the German-speaking study sites, an extension to other participating countries will be decided during the study, the assessment of cost-effectiveness will be realised by comparing cost-results with regard to changes in QoL	one to five years

External Links

•   EU-CERT-ICD Website