Clinical trial NCT00619593: Survival of Patients With Primary Prophylactic ICD Indication
Official title: Survival of Patients With Primary Prophylactic ICD Indication, Provided With Intensified Care After 1st ICD Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Prevention
Tachycardia, Ventricular
Sudden Cardiac Death
Keywords: Heart failure
Ventricular Fibrillation
Sudden cardiac death
Hospitalization due to heart failure
Implantable cardioverter-defibrillator
Risk of 1st heart failure hospitalization
Lead sponsor: Biotronik SE & Co. KG
Sponsor class: INDUSTRY
First posted: 2008-02-21
Enrollment: 504
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The MADIT-II trial has shown that patients with severely reduced left ventricular ejection fraction (LVEF) post myocardial infarction benefit from the implantable cardioverter-defibrillator (ICD). However, retrospective analyses of the MADIT-II data have revealed a significantly increased morbidity and mortality in patients with appropriate ICD therapy: Appropriate ICD therapy is associated with 3.3-fold increased all-cause mortality, and the risk of a first heart failure hospitalization is 90% higher after 1st appropriate ICD therapy. Hence, the 1st appropriate therapy might indicate the necessity and utility of further clinical diagnostics and therapy in these patients.

This trial is designed to (i) improve the knowledge of the group characteristics of patients suffering from 1st appropriate ICD therapy, (ii) but moreover to take additional therapeutic steps to reduce the mortality of this patient population.

Detailed description: The MADIT-II trial has shown that patients with severely reduced left ventricular ejection fraction (LVEF) post myocardial infarction benefit from the implantable cardioverter-defibrillator (ICD). However, retrospective analyses of the MADIT-II data have revealed a significantly increased morbidity and mortality in patients with appropriate ICD therapy: Appropriate ICD therapy is associated with 3.3-fold increased all-cause mortality, and the risk of a first heart failure hospitalization is 90% higher after 1st appropriate ICD therapy. Hence, the 1st appropriate therapy might indicate the necessity and utility of further clinical diagnostics and therapy in these patients.

This trial is designed to (i) improve the knowledge of the group characteristics of patients suffering from 1st appropriate ICD therapy, (ii) but moreover to take additional therapeutic steps to reduce the mortality of this patient population.

After standard ICD implantation procedure, the following steps are performed at the pre-discharge follow-up:

* Programming: VR-T: VVI 40 ppm, Onset 20%, Stability 20 ms
* DR-T: DDD 50-60 ppm, activation of IRSplus and SMART
* HF-T: DDD-BiV 50-60 ppm, achieve at least 85% biventricular resynchronisation, activation of SMART
* All devices: VT zone as therapy zone, VF zone. Programming recommendations for VT/VF zones to standardize treatment:

  * VF zone: 200-250 bpm/ 300-240 ms, ATPoneshot ON
  * VT1 zone: 167-200 bpm/ 360-300 ms, ATP ON
  * VT2 zone: 120-167 bpm/ 500-360 ms, ATP ON
* Activation of Home Monitoring (HM) and online registration for HM service

Standard Follow-up: Timing and scope of follow-up in patients without episodes is to the physician's own discretion and should follow the standard clinical routine.

Follow-up after 1st appropriate ICD therapy: Immediately after having received the 1st appropriate ICD therapy, the patients have to be called to the clinic for intensified clinical diagnostics and, if necessary or useful, intensified therapy. Standard ICD follow-up has to be started within 72 hours after 1st appropriate ICD therapy.

* ICD interrogation
* General health status (weight, BP, NYHA)
* Laboratory tests (hemoglobin, Nt-proBNP, creatinine, GDF-15)
* Echocardiography (LVEF, LVEDD, mitral regurgitation)
* Non-invasive ischemia evaluation
* Coronary angiography (if indicated by ischemia evaluation)
* Upgrade to CRT, if indicated
* Ventricular ablation (if indicated: VT storm, slow VT, bundle branch reentry)
* 24 hrs ECG Holter (Heart rate variability)
* Further treatment (if applicable)
* Changes in ICD settings, or medication
* Adverse events / adverse device effects

Final follow-up visit: For patients without appropriate ICD therapy, the final follow-up shall be performed 12 months after enrolment.

For patients with appropriate ICD therapy, the final follow-up shall be performed 12 months after 1st appropriate ICD therapy.

The final follow-up visit comprises:

* ICD interrogation
* General health status (weight, BP, NYHA)
* Echocardiography (LVEF, LVEDD, mitral regurgitation)
* Laboratory tests (hemoglobin, Nt-proBNP, creatinine, GDF-15)
* 24 hrs ECG Holter (Heart rate variability)
* Further treatment (if applicable)
* Changes in ICD settings, or medication
* Adverse events / adverse device effects

Eligibility criteria: Inclusion Criteria:

* Indication for ICD implantation according to MADIT-II:

  * Myocardial infarction 30 days or more before implantation
  * LVEF of 30% or less within 3 months before implantation
* Angiography within the preceding 12 months
* The patient is willing and able to comply with the clinical investigation plan and has provided written informed consent

Exclusion Criteria:

* Patients with contraindication for ICD implantation
* Conventional ICD indication (i.e. other than MADIT-II)
* Myocardial infarction within the past 30 days
* Coronary revascularisation within the preceding 3 months (i.e., if revascularization has been performed wait at least 3 months until enrolment, given that no appropriate/ inappropriate ICD therapy has occured)
* NYHA functional class IV
* Unexplained syncope within 3 years
* Advanced cerebrovascular disease
* Life expectancy very probably below 12 months
* Pregnant or breast-feeding women
* Age \< 18 years
* Patients who are already enrolled in another study (therapy/intervention phase)

Primary outcomes:
measure: Mortality
timeFrame: 12 months
Secondary outcomes:
measure: Sudden cardiac death
timeFrame: 12 months
measure: Non-sudden cardiac death
timeFrame: 12 months
measure: Risk of 1st heart failure hospitalization
timeFrame: 12 months
measure: No. of VT Storms (> 3 VT/24h)
timeFrame: 12 months
measure: No. of delivered ICD therapies
timeFrame: 12 months
Other outcomes:
Locations:
city: Linz
country: Austria
facility: A.ö. Krankenhaus der Stadt Linz
city: St. Poelten
country: Austria
facility: Landesklinikum St. Pölten
city: Wien
country: Austria
facility: Wilhelminenspital der Stadt Wien
city: Brno
country: Czech Republic
facility: Brno Bohunice
city: Brno
country: Czech Republic
facility: Fakultni nemocnice u Svety Anny
city: Olomouc
country: Czech Republic
facility: FN Olomouc, Inerni klinika
city: Praha
country: Czech Republic
facility: Online 24 S.R.O.
city: Praha
country: Czech Republic
facility: Institute of clinical and experimental medicine
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen
city: Bad Neustadt
country: Germany
facility: Herz- und Gefäss-Klinik GmbH Bad Neustadt
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Bonn
country: Germany
facility: St. Marien Hospital
city: Detmold
country: Germany
facility: Klinikum Detmold Lippe
city: Dortmund
country: Germany
facility: Klinikum Mitte
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden-Friedrichstadt
city: Düsseldorf
country: Germany
facility: Evangelisches Krankenhaus
city: Erkelenz
country: Germany
facility: Hermann-Josef-Krankenhaus
city: Gießen
country: Germany
facility: Justus Liebig Universität Gießen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Landshut
country: Germany
facility: Krankenhaus Landshut-Achdorf
city: Mönchengladbach
country: Germany
facility: Krankenhaus St. Franziskus
city: Paderborn
country: Germany
facility: St. Vincenz Krankenhaus
city: Rostock
country: Germany
facility: University Hospital Rostock
city: Unna
country: Germany
facility: Katharinenhospital
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: The University of Medicine Debrecen
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Riga
country: Latvia
facility: Latvian Center of Cardiology
city: Hamilton
country: New Zealand
facility: Health Waikato, Cardiology Department
city: Lodz
country: Poland
facility: MULTI-MED PLUS Spolka z o.o
city: Warzawa
country: Poland
facility: Instytut Kardiologii
city: Banska Bystrica
country: Slovakia
facility: Ssusch
city: Bratislava
country: Slovakia
facility: Kardiologická klinika
city: Kosice
country: Slovakia
facility: VUSCH East Slovak Cardiology Institute
city: Valencia
country: Spain
facility: H. Univ. La Fe
city: Basel
country: Switzerland
facility: Universitätsspital Basel
Study officials:
affiliation: Národný ústav srdcových a cievnych chorôb, Kardiologická klinika, Pod Krásnou Hôrkou 1, 833 48 Bratislava, Slovakia
name: Robert Hatala, Prof. MUDr.
role: PRINCIPAL_INVESTIGATOR
References: