Clinical trial NCT04014946: Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy
Official title: Prospective Assessment of Risk Factors for Appropriate ICD Intervention in Patients With Ischemic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ICD
Cardiomyopathy Ischemic
Primary Prevention
Lead sponsor: Biotronik SE & Co. KG
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study model is single group. At the analysis the patients will be divided in two groups bij outcome of ICD therapy/no ICD therapy.

The endpoints related to the primary hypothesis are appropriate ICD intervention (shock or ATP) and Relative Infarct Transmurality (RIT = transmural infarct mass / total infarct mass) obtained from LGE-CMR. ICD interventions will be labeled appropriate or non-appropriate by an independent endpoint committee.

* RITshock or ATP: RIT expectation value in patients with ≥1 appropriate shock or ATP therapy until the 24mo follow-up
* RIT no shock or ATP: RIT expectation value in patients without any appropriate shock or ATP therapy until the 24mo follow-up
Primary purpose: PREVENTION

Brief summary: Design: PARCADIA is a prospective non-randomized non-interventional multi-center clinical investigation in Europe. Patients with depressed LV (left ventricular) function assessed on local standards, of ischemic origin and on chronic optimal medical therapy will be selected according to inclusion and exclusion criteria, implanted with an ICD after executing baseline investigations and prospectively followed up for minimal 24 months and until the termination of the clinical investigation.

General objective: analysis of baseline risk factors to identify predictors for appropriate ICD intervention in patients with ischemic cardiomyopathy receiving an ICD for primary prevention (MADIT II population).

Hypothesis: The primary alternative hypothesis states that the mean relative infarct transmurality (RIT) is different in patients with (RITshock or ATP (Anti Tachy Pacing)) and without (RITno shock or ATP )appropriate ICD intervention, i.e. shock or ATP.

* Null hypothesis (H0): RITshock or ATP = RITno shock or ATP
* Alternative hypothesis (Ha): RITshock or ATP ≠ RITno shock or ATP

Sample size: 200 patients.

Follow-up: Enrolment visit, pre implant screening, ICD implantation, pre-hospital discharge visit, and follow-up (FUP) visits at 2, 6, 12, 18, 24 months including home monitoring. Additional routine FUP every 6 months until study termination after last enrolled patient has completed 2 years FUP.

Detailed description: Rationale: Implantation of an ICD as primary prevention therapy is indicated according to the current guidelines based on the low LVEF (Left Ventricular Ejection Fraction) as it was shown to significantly reduce mortality. Although of proven efficacy, ICD therapy is associated with survival benefit in only a small fraction of patients. It is estimated that 18 patients would have to receive an ICD to save one life, resulting in a huge burden on national health systems. Moreover, only about one quarter of all guideline eligible primary prevention ICD patients receive appropriate shocks. The above considerations support the need for an effective risk-stratification method to identify patients that benefit most (or least) from this therapy. Evaluation of ventricular anatomy and function by imaging techniques has become more important since this provides information on the substrate (myocardial scar) and trigger of life-threatening ventricular arrhythmias. Besides accurate estimation of left and right ventricular volumes and functions, Late Gadolinium Enhanced Cardiac Magnetic Resonance (LGE-CMR) imaging has a very high sensitivity to detect myocardial scar. Quantification of scar characteristics by cardiac MRI might be useful for the prediction of future arrhythmic events in patients with ischemic cardiomyopathy. However evidence is conflicting and published papers are hampered by limited patient numbers and can only be regarded in the light of generating hypothesis. The PARCADIA clinical investigation will explore the potential of cardiac MRI as a predictor for appropriate ICD intervention in a multicenter setting.

PARCADIA is a prospective non-randomized non-interventional multi-center clinical investigation in Europe. Patients with depressed LV (Left Ventricular) function assessed on local standards, of ischemic (at least 40 days post-MI (myocardial infarction) or 3 months post revascularization) origin and on chronic optimal medical therapy will be selected according to inclusion and exclusion criteria, implanted with an ICD after executing baseline investigations and prospectively followed up for minimal 24 months and until the termination of the clinical investigation

General objective: analysis of baseline risk factors to identify predictors for appropriate ICD intervention in patients with ischemic cardiomyopathy receiving an ICD for primary prevention (MADIT II population).

The primary objective of the clinical investigation is to determine whether there is a relationship between appropriate ICD intervention (shock or ATP) and the Relative Infarct Transmurality (RIT) obtained from Late Gadolinium Enhanced Cardiac Magnetic Resonance (LGE-CMR) imaging in patients with ischemic cardiomyopathy, receiving an ICD for primary prevention.

Methodology: Screening: (within 6 months before enrolment) patients with LV depressed function due to Ischemic Cardiomyopathy with an indication for primary prevention ICD implantation according to ESC (European Society of Cardiology) guidelines or local standards will be screened within 6 months before enrolment.

pre implant diagnostics: within 3 months after enrolment LGE-CMR imaging, 24h holter, 12-lead ECG, will be performed and biochemical markers will be obtained.

ICD implantation: Implantation of a Lumax 540 single/dual chamber ICD or successor withiin 3 months after enrolment. The ICD will be programmed according to protocol.

Pre-hospital discharge an ICD interrogation wil be performed. Follow-up (FUP) visits at: 2, 6, 12, 18, 24 months with inclusion of standard 12-lead ECG, ICD check-up and cardiologist visit in the outpatient clinic. Additional routine FUP every 6 months until study termination after last enrolled patient has completed 2 years FUP.

Eligibility criteria: Inclusion Criteria:

* Patient with ischemic cardiomyopathy indicated for a de novo ICD implantation for primary prevention, according to ESC guidelines or local standards (MADIT II population)
* Written informed consent / willingness and ability to comply with the protocol

Exclusion Criteria:

* Contraindication for MRI
* Severe renal dysfunction (stage 4 or 5) resulting in contra-indication for the admission of gadolinium during MRI (See Appendix A for more details)
* Indication for secondary prevention ICD implantation
* Class I indication for cardiac resynchronization therapy
* Heart failure with New York Heart Association functional class IV
* LV ejection fraction \>40%
* Age \<18 years and \>85 years
* Women that are pregnant, lactating or planning to become pregnant
* Participating in any other clinical trial with active intervention(s) during the course of this study
* Life expectancy less than 1 year

Primary outcomes:
measure: Relative Infarct Transmurality
timeFrame: Measured during Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging within 3 months after inclusion and before ICD implantation
measure: appropriate ICD intervention (shock or ATP)
timeFrame: Until the 24 month follow-up
Secondary outcomes:
measure: LV function (EF)
timeFrame: Baseline
measure: LV mass
timeFrame: Baseline
measure: total infarct mass
timeFrame: Baseline
measure: transmural infarct mass
timeFrame: Baseline
measure: mean Heart Rate (HR)
timeFrame: Baseline
measure: Day and night HR
timeFrame: baseline
measure: spontaneous episodes of atrial and ventricular arrhythmias
timeFrame: baseline
measure: heart rate variability (SDNN: Standard deviation of consecutive normal-to-normal intervals)
timeFrame: baseline
measure: HR
timeFrame: baseline
measure: rhythm
timeFrame: baseline
measure: QRS width
timeFrame: baseline
measure: serum sodium and potassium
timeFrame: baseline
measure: serum creatinine
timeFrame: baseline
measure: uric acid
timeFrame: baseline
measure: albumin
timeFrame: baseline
measure: HbA1c (Hemoglobin A1c)
timeFrame: baseline
measure: NT-proBNP (N-terminal pro-hormone Brain Natriuretic Peptide)
timeFrame: baseline
measure: hsTNT/I (high sensitive Troponin-T/I)
timeFrame: baseline
measure: aldosterone
timeFrame: baseline
measure: incidence of hypertension
timeFrame: baseline
measure: incidence of diabetes
timeFrame: baseline
measure: incidence of hypercholesterolemia
timeFrame: baseline
measure: PVC/hr: Premature ventricular contraction per hour
timeFrame: baseline
Other outcomes:
Locations:
Study officials:
References: