IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction

Study Overview
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Brief Summary
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The primary objective is to evaluate the safety and effectiveness of the IK-5001 device for the prevention of ventricular remodeling and congestive heart failure when administered to subjects who had successful percutaneous coronary intervention with stent placement after ST segment elevation MI (STEMI).

Detailed Description
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Heart failure is a significant problem, and carries substantial mortality. According to studies, left ventricular (LV) remodeling contributes independently to heart failure progression. Prevention and reversal of LV remodeling are correlated with decreased risk of death and heart failure events. IK-5001 is an implantable device to be used in subjects with recent myocardial infarction (MI). The IK-5001 device has been shown to directly halt the remodeling process that occurs following acute MI. IK-5001 replaces the damaged extracellular matrix (ECM) that has degraded during infarction, supports the damaged myocardial tissue, prevents local dyskinesis, and decreases wall stress. Because of its minimal interaction with the myocardium, its mechanism of action, its lack of specific pharmacologic activity and its elimination behavior, IK-5001 is a medical device in concurrence with the Global Harmonization Task Force's harmonized definition for medical devices.

Official Title
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A Placebo Controlled, Multicenter, Randomized Double Blind Trial to Evaluate the Safety and Effectiveness of IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction, Congestive Heart Failure, ST-Elevation Myocardial Infarction

Intervention / Treatment
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* Device: IK-5001
* Device: Saline Solution


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects must meet all of the following inclusion criteria to participate in this trial: The subject is ≥ 18 years of age. The subject has given informed consent. The subject has experienced a large STEMI defined by the following criteria: Peak cardiac enzyme value within 48 hours of symptom onset as follows: Creatine kinase MB fraction (CK-MB) > 30 x the upper limit of normal OR Troponin I > 200 x upper limit of normal OR Troponin T > 60 x the upper limit of normal AND at least 1 of the following 3 criteria: Delayed presentation with PCI > 6 hours from onset of symptoms Significant new Q waves in ≥ 2 anterior leads or anterior ST segment elevation of at least 3 mm persistent at 24 hours after PCI New onset of CHF (Killip class 3-4) or cardiogenic shock persistent at 24 hours after PCI AND at least 1 of the following 2 criteria: MI ≥ 20% by Single Photon Emission Computed Tomography scan (SPECT) or cardiac Magnetic Resonance Imaging (MRI) with defect in the appropriate distribution Ejection fraction ≤ 35% with wall motion abnormality in the appropriate distribution at baseline imaging assessment The subject has had successful PCI with stent within 48 hours of symptom onset, and residual stenosis less than 20% in the infarct related artery and greater than or equal to thrombolysis in myocardial infarction (TIMI) 2 flow. Subjects undergoing rescue PCI after thrombolysis or delayed presentation with ongoing ischemia may be enrolled. For Germany only: Patients determined to have Killip class 4 at time of device deployment are not eligible for randomization. For Germany only: If SPECT is used for determination of MI size in order to meet inclusion criteria, the SPECT must have been previously performed as part of standard clinical care. SPECT is not to be performed solely to qualify a patient for this study in Germany. Exclusion criteria: Subjects will be excluded from participating in this trial if ANY of the following exclusion criteria are met: Any subject with cardiogenic shock requiring mechanical ventilation or mechanical support at the time of deployment. Subject must be off mechanical support prior to deployment. Need for urgent coronary artery bypass graft (CABG) Clinically significant valvular heart disease with planned surgical correction or transcatheter aortic valve implantation (TAVI) Uncontrolled ventricular arrhythmias Renal insufficiency with a calculated creatinine clearance of less than 30 mL/ minute. See Appendix A for determining estimated creatinine clearance. Clinically significant hepatic insufficiency Inadequate imaging windows (defined as the inability to visualize the endocardial border of at least 16 of the 17 segments in both the apical four chambers and apical two chamber views without foreshortening) or arrhythmia that would preclude adequate 3D imaging on transthoracic echocardiography at the local baseline echo assessment Non-ambulatory prior to the index MI The subject has participated in another trial of an investigational agent within 30 days prior to randomization. Subject has received resorbable stent as part of PCI. The subject is pregnant or breastfeeding. Women of child-bearing potential will have a negative urine pregnancy test prior to randomization. Any other concurrent condition that, in the opinion of the investigator, would prevent completion of the clinical trial, including inability to comply with follow up requirements. For Germany only: In the investigator's opinion, the patient is not expected to survive ≥12 months. For Germany only: 24 hours prior to device deployment, the patient has a serum calcium level greater than the upper limit of normal as determined by the local laboratory.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effects of IK-5001. 306 trials randomized 2:1 active vs placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IK-5001<br>IK-5001 Sodium Alginate Calcium Gluconate intracoronary injection | Device: IK-5001<br>* 4 mL (+/- 0.2 mL) administered through intracoronary slow bolus injection over 15 to 30 seconds at least 2 days after PCI but within 5 days of onset of symptoms.<br>* Other names: BIOABSORBABLE CARDIAC MATRIX (BCM);|
| Placebo Comparator: Saline Solution<br>Saline Solution intracoronary injection | Device: Saline Solution<br>* 4 mL (+/- 0.2 mL) slow bolus, intracoronary injection of saline solution will be administered over 15 to 30 seconds at least 2 days after percutaneous coronary intervention (PCI) but within 5 days of onset of symptoms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular End Diastolic Volume Index | Anatomic measurement of left ventricular end diastolic volume index (LVEDVI) assessed through echocardiogram. | Baseline, 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kansas City Cardiomyopathy Questionaire | Patient reported outcomes (PROs) using The Kansas City Cardiomyopathy Questionaire (KCCQ) score - a validated disease-specific self-administered 23-item questionnaire that will be used to quantify symptoms, function, and quality of life of subjects. | Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits | 
| Six minute walk test | The six minute walk test (6MWT) is used for measuring the response to medical interventions in subjects with moderate to severe heart disease, functional status of subjects, as well as a predictor of morbidity and mortality | Baseline (prior to discharge STEMI), 1, 3, 6 and 12 month follow-up visits | 
| New York Heart Association (NYHA) functional classification (Physician reported) | New York Heart Association (NYHA) classification assessed by physician will be categorized by Class (Class I - IV) | Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits | 
| Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations | Time to cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations adjudicated by a Clinical Events Committee | 5 Years | 
| Re-hospitalization due to any cardiovascular event | Time to re-hospitalization due to any cardiovascular event | 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STEMI, Acute Myocardial Infarction, Congestive Heart Failure, Left Ventricular Remodeling, Devices, Medical