Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy (PARCADIA)

Prospective Assessment of Risk Factors for Appropriate ICD Intervention in Patients With Ischemic Cardiomyopathy

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.

Study Overview

• Status: Completed
• Conditions: Primary Prevention; ICD; Cardiomyopathy Ischemic
• Intervention / Treatment: Device: ICD implantation

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: ICD implantation; Implantation of a Lumax 540 single/dual chamber ICD or successor according to local practice within 3 months after enrolment. The patient will be implanted with a single or dual chamber device according to ESC guidelines.	Device: ICD implantation; implantation of the Lumax 540 single/dual chamber ICD or successor; Other Names: Lumax 540 single/dual chamber ICD or successor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Infarct Transmurality	Percentage Relative Infarct Transmurality (RIT = transmural infarct mass / total infarct mass) obtained from LGE-CMR	Measured during Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging within 3 months after inclusion and before ICD implantation
appropriate ICD intervention (shock or ATP)	assessment whether patient had appropriate ICD intervention (shock or ATP) or not during 24 months follow-up. ICD interventions will be labeled appropriate or non-appropriate by an independent endpoint committee.	Until the 24 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV function (EF)	Left Ventricular function (Ejection Fraction in %) measured during LGE-CMR at baseline before ICD implantation	Baseline
LV mass	LV mass measured during LGE-CMR at baseline before ICD implantation	Baseline
total infarct mass	total infarct mass measured during GGE-CMR at baseline before ICD implantation	Baseline
transmural infarct mass	transmural infarct mass measured during LGE-CMR at baseline before ICD implantation	Baseline
mean Heart Rate (HR)	mean HR measured by 24-hrs Holter	Baseline
Day and night HR	Day and night HR measured by 24-hrs Holter	baseline
spontaneous episodes of atrial and ventricular arrhythmias	number of spontaneous episodes of atrial and ventricular arrhythmias measured by 24-hrs Holter	baseline
heart rate variability (SDNN: Standard deviation of consecutive normal-to-normal intervals)	heart rate variability (SDNN) measured by 24-hrs Holter	baseline
HR	HR on 12 lead ECG	baseline
rhythm	rhythm on 12 lead ECG	baseline
QRS width	QRS width on 12 lead ECG	baseline
serum sodium and potassium	concentration of serum sodium and potassium (in mmol/l ) (blood sample)	baseline
serum creatinine	concentration of serum creatinine (in umol/l) (blood sample)	baseline
uric acid	concentration of uric acid (in mmol/l) (blood sample)	baseline
albumin	concentration of albumin (in g/l) (blood sample)	baseline
HbA1c (Hemoglobin A1c)	concentration HbA1c (mmol/mol) (blood sample)	baseline
NT-proBNP (N-terminal pro-hormone Brain Natriuretic Peptide)	concentration NT-proBNP (in pg/ml) (blood sample)	baseline
hsTNT/I (high sensitive Troponin-T/I)	concentration hsTNT/I (in ng/ml) (blood sample)	baseline
aldosterone	concentration aldosterone (in pmol/l) (blood sample)	baseline
incidence of hypertension	Baseline clinical demographics: hypertension in clinical history	baseline
incidence of diabetes	Baseline clinical demographics: diabetes in clinical history	baseline
incidence of hypercholesterolemia	Baseline clinical demographics: hypercholesterolemia in clinical history	baseline
PVC/hr: Premature ventricular contraction per hour	PVC/hr: Premature ventricular contraction per hour on 24hrs Holter	baseline

Collaborators and Investigators

• Sponsor: Biotronik SE & Co. KG

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 24, 2012
• Primary Completion (ACTUAL): May 28, 2020
• Study Completion (ACTUAL): July 22, 2020

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (ACTUAL): July 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Ischemia; Cardiomyopathies
• Other Study ID Numbers: TA97

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No