Survival of Patients With Primary Prophylactic ICD Indication (SPIRIT-ICD)

Survival of Patients With Primary Prophylactic ICD Indication, Provided With Intensified Care After 1st ICD Therapy

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.

Study Overview

• Status: Completed
• Conditions: Tachycardia, Ventricular; Primary Prevention; Sudden Cardiac Death
• Intervention / Treatment: Other: Standard follow-up; Other: Intensified diagnostic and treatment measures following 1st appropriate ICD therapy

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

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4020
    • A.ö. Krankenhaus der Stadt Linz
  • St. Poelten, Austria, 3100
    • Landesklinikum St. Pölten
  • Wien, Austria, 1160
    • Wilhelminenspital der Stadt Wien
• Czech Republic
  • Brno, Czech Republic, 62500
    • Brno Bohunice
  • Brno, Czech Republic, 65691
    • Fakultni nemocnice u Svety Anny
  • Olomouc, Czech Republic, 77520
    • FN Olomouc, Inerni klinika
  • Praha, Czech Republic, 12000
    • Online 24 S.R.O.
  • Praha, Czech Republic, 1421
    • Institute of clinical and experimental medicine
• Germany
  • Aachen, Germany, 52074
    • University Hospital RWTH Aachen
  • Bad Neustadt, Germany, 97616
    • Herz- und Gefäß-Klinik GmbH Bad Neustadt
  • Bielefeld, Germany, 33604
    • Klinikum Bielefeld
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Bonn, Germany, 53115
    • St. Marien Hospital
  • Detmold, Germany, 32756
    • Klinikum Detmold Lippe
  • Dortmund, Germany, 44137
    • Klinikum Mitte
  • Dresden, Germany, 01067
    • Städtisches Klinikum Dresden-Friedrichstadt
  • Düsseldorf, Germany, 40217
    • Evangelisches Krankenhaus
  • Erkelenz, Germany, 41812
    • Hermann-Josef-Krankenhaus
  • Gießen, Germany, 35392
    • Justus Liebig Universitat Gießen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Landshut, Germany, 84034
    • Krankenhaus Landshut-Achdorf
  • Mönchengladbach, Germany, 41063
    • Krankenhaus St. Franziskus
  • Paderborn, Germany, 33098
    • St. Vincenz Krankenhaus
  • Rostock, Germany, 18055
    • University Hospital Rostock
  • Unna, Germany, 59423
    • Katharinenhospital
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis University
  • Debrecen, Hungary, 4012
    • The University of Medicine Debrecen
• Israel
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
• Latvia
  • Riga, Latvia, 1002
    • Latvian Center of Cardiology
• New Zealand
  • Hamilton, New Zealand
    • Health Waikato, Cardiology Department
• Poland
  • Lodz, Poland, 95336
    • MULTI-MED PLUS Spolka z o.o
  • Warzawa, Poland, 04-628
    • Instytut Kardiologii
• Slovakia
  • Banska Bystrica, Slovakia, 97401
    • Ssusch
  • Bratislava, Slovakia, 833 48
    • Kardiologicka klinika
  • Kosice, Slovakia, 04001
    • Vusch East Slovak Cardiology Institute
• Spain
  • Valencia, Spain, 46009
    • H. Univ. La Fe
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2; Standard follow-up in patients without appropriate ICD therapy	Other: Standard follow-up; Standard follow-up in patients without appropriate ICD therapy
Experimental: 1; Following 1st appropriate ICD therapy, the patients have to be called to the clinic for intensified clinical diagnostics and, if necessary or useful, intensified therapy.	Other: Intensified diagnostic and treatment measures following 1st appropriate ICD therapy; Assessment of 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; Other Names: Intensified diagnostic and treatment measures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Sudden cardiac death	12 months
Non-sudden cardiac death	12 months
Risk of 1st heart failure hospitalization	12 months
No. of VT Storms (> 3 VT/24h)	12 months
No. of delivered ICD therapies	12 months

Collaborators and Investigators

• Sponsor: Biotronik SE & Co. KG
• Investigators: Principal Investigator: Robert Hatala, Prof. MUDr., Národný ústav srdcových a cievnych chorôb, Kardiologická klinika, Pod Krásnou Hôrkou 1, 833 48 Bratislava, Slovakia

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 11, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: January 9, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Heart failure; Sudden cardiac death; Ventricular Fibrillation; Hospitalization due to heart failure; Implantable cardioverter-defibrillator; Risk of 1st heart failure hospitalization
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Arrest; Death; Tachycardia; Tachycardia, Ventricular; Death, Sudden, Cardiac
• Other Study ID Numbers: TA079