Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy (PARCADIA)
Primary Purpose
ICD, Cardiomyopathy Ischemic, Primary Prevention
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
ICD implantation
Sponsored by
About this trial
This is an interventional prevention trial for ICD
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
ICD implantation
Arm Description
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.
Outcomes
Primary Outcome Measures
Relative Infarct Transmurality
Percentage Relative Infarct Transmurality (RIT = transmural infarct mass / total infarct mass) obtained from LGE-CMR
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.
Secondary Outcome Measures
LV function (EF)
Left Ventricular function (Ejection Fraction in %) measured during LGE-CMR at baseline before ICD implantation
LV mass
LV mass measured during LGE-CMR at baseline before ICD implantation
total infarct mass
total infarct mass measured during GGE-CMR at baseline before ICD implantation
transmural infarct mass
transmural infarct mass measured during LGE-CMR at baseline before ICD implantation
mean Heart Rate (HR)
mean HR measured by 24-hrs Holter
Day and night HR
Day and night HR measured by 24-hrs Holter
spontaneous episodes of atrial and ventricular arrhythmias
number of spontaneous episodes of atrial and ventricular arrhythmias measured by 24-hrs Holter
heart rate variability (SDNN: Standard deviation of consecutive normal-to-normal intervals)
heart rate variability (SDNN) measured by 24-hrs Holter
HR
HR on 12 lead ECG
rhythm
rhythm on 12 lead ECG
QRS width
QRS width on 12 lead ECG
serum sodium and potassium
concentration of serum sodium and potassium (in mmol/l ) (blood sample)
serum creatinine
concentration of serum creatinine (in umol/l) (blood sample)
uric acid
concentration of uric acid (in mmol/l) (blood sample)
albumin
concentration of albumin (in g/l) (blood sample)
HbA1c (Hemoglobin A1c)
concentration HbA1c (mmol/mol) (blood sample)
NT-proBNP (N-terminal pro-hormone Brain Natriuretic Peptide)
concentration NT-proBNP (in pg/ml) (blood sample)
hsTNT/I (high sensitive Troponin-T/I)
concentration hsTNT/I (in ng/ml) (blood sample)
aldosterone
concentration aldosterone (in pmol/l) (blood sample)
incidence of hypertension
Baseline clinical demographics: hypertension in clinical history
incidence of diabetes
Baseline clinical demographics: diabetes in clinical history
incidence of hypercholesterolemia
Baseline clinical demographics: hypercholesterolemia in clinical history
PVC/hr: Premature ventricular contraction per hour
PVC/hr: Premature ventricular contraction per hour on 24hrs Holter
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04014946
Brief Title
Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy
Acronym
PARCADIA
Official Title
Prospective Assessment of Risk Factors for Appropriate ICD Intervention in Patients With Ischemic Cardiomyopathy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
July 24, 2012 (Actual)
Primary Completion Date
May 28, 2020 (Actual)
Study Completion Date
July 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotronik SE & Co. KG
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ICD, Cardiomyopathy Ischemic, Primary Prevention
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ICD implantation
Arm Type
Other
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
ICD implantation
Other Intervention Name(s)
Lumax 540 single/dual chamber ICD or successor
Intervention Description
implantation of the Lumax 540 single/dual chamber ICD or successor
Primary Outcome Measure Information:
Title
Relative Infarct Transmurality
Description
Percentage Relative Infarct Transmurality (RIT = transmural infarct mass / total infarct mass) obtained from LGE-CMR
Time Frame
Measured during Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging within 3 months after inclusion and before ICD implantation
Title
appropriate ICD intervention (shock or ATP)
Description
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.
Time Frame
Until the 24 month follow-up
Secondary Outcome Measure Information:
Title
LV function (EF)
Description
Left Ventricular function (Ejection Fraction in %) measured during LGE-CMR at baseline before ICD implantation
Time Frame
Baseline
Title
LV mass
Description
LV mass measured during LGE-CMR at baseline before ICD implantation
Time Frame
Baseline
Title
total infarct mass
Description
total infarct mass measured during GGE-CMR at baseline before ICD implantation
Time Frame
Baseline
Title
transmural infarct mass
Description
transmural infarct mass measured during LGE-CMR at baseline before ICD implantation
Time Frame
Baseline
Title
mean Heart Rate (HR)
Description
mean HR measured by 24-hrs Holter
Time Frame
Baseline
Title
Day and night HR
Description
Day and night HR measured by 24-hrs Holter
Time Frame
baseline
Title
spontaneous episodes of atrial and ventricular arrhythmias
Description
number of spontaneous episodes of atrial and ventricular arrhythmias measured by 24-hrs Holter
Time Frame
baseline
Title
heart rate variability (SDNN: Standard deviation of consecutive normal-to-normal intervals)
Description
heart rate variability (SDNN) measured by 24-hrs Holter
Time Frame
baseline
Title
HR
Description
HR on 12 lead ECG
Time Frame
baseline
Title
rhythm
Description
rhythm on 12 lead ECG
Time Frame
baseline
Title
QRS width
Description
QRS width on 12 lead ECG
Time Frame
baseline
Title
serum sodium and potassium
Description
concentration of serum sodium and potassium (in mmol/l ) (blood sample)
Time Frame
baseline
Title
serum creatinine
Description
concentration of serum creatinine (in umol/l) (blood sample)
Time Frame
baseline
Title
uric acid
Description
concentration of uric acid (in mmol/l) (blood sample)
Time Frame
baseline
Title
albumin
Description
concentration of albumin (in g/l) (blood sample)
Time Frame
baseline
Title
HbA1c (Hemoglobin A1c)
Description
concentration HbA1c (mmol/mol) (blood sample)
Time Frame
baseline
Title
NT-proBNP (N-terminal pro-hormone Brain Natriuretic Peptide)
Description
concentration NT-proBNP (in pg/ml) (blood sample)
Time Frame
baseline
Title
hsTNT/I (high sensitive Troponin-T/I)
Description
concentration hsTNT/I (in ng/ml) (blood sample)
Time Frame
baseline
Title
aldosterone
Description
concentration aldosterone (in pmol/l) (blood sample)
Time Frame
baseline
Title
incidence of hypertension
Description
Baseline clinical demographics: hypertension in clinical history
Time Frame
baseline
Title
incidence of diabetes
Description
Baseline clinical demographics: diabetes in clinical history
Time Frame
baseline
Title
incidence of hypercholesterolemia
Description
Baseline clinical demographics: hypercholesterolemia in clinical history
Time Frame
baseline
Title
PVC/hr: Premature ventricular contraction per hour
Description
PVC/hr: Premature ventricular contraction per hour on 24hrs Holter
Time Frame
baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy
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