Principal Investigator: J .Dawn Abbott, M.D.
Rhode Island Hospital and Miriam Hospital
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
This is a phase 2, multicenter, randomized, double blind, placebo-controlled trial to evaluate the effects of IK-5001 for the prevention of ventricular remodeling and congestive heart failure after acute STEMI. This trial will include subjects who had successful percutaneous coronary intervention (PCI) with stent placement after STEMI. These subjects are at high risk of developing left ventricular remodeling that may lead to heart failure events. A total of 306 subjects will be randomized. Subjects will be randomized in a 2:1 ratio to receive 4 mL of IK-5001 or saline control. Safety and effectiveness assessments will be performed following randomization at baseline (prior to device deployment), following device deployment, and at follow-up visits up to 5 years after device deployment. Follow-up visits will be scheduled at 1, 3, 6 and 12 months and then at least annually for up to 4 years after the 12-month visit.
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 STEMI.
Subjects must meet all of the following inclusion criteria to participate in this trial:
1. The subject is ≥ 18 years of age.
2. The subject has given informed consent.
3. 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
• 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 congestive heart failure (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 MRI with defect in the appropriate distribution
• Ejection fraction ≤ 35% with wall motion abnormality in the appropriate distribution at baseline imaging assessment
4. 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 TIMI 2 flow. Subjects undergoing rescue PCI after thrombolysis or delayed presentation with ongoing ischemia may be enrolled.
5. For Germany only: Patients determined to have Killip class 4 at time of device deployment are not eligible for randomization.
6. 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.
Subjects will be excluded from participating in this trial if ANY of the following exclusion criteria
1. 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.
2. Need for urgent coronary artery bypass graft (CABG)
3. Clinically significant valvular heart disease with planned surgical correction or transcatheter aortic valve implantation (TAVI)
4. Uncontrolled ventricular arrhythmias
5. Renal insufficiency with a calculated creatinine clearance of less than 30 mL/ minute.
6. Clinically significant hepatic insufficiency
7. 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
8. Non-ambulatory prior to the index MI
9. The subject has participated in another trial of an investigational agent within 30 days prior to randomization.
10. Subject has received resorbable stent as part of PCI
11. The subject is pregnant or breastfeeding. Women of child-bearing potential will have a negative urine pregnancy test prior to randomization.
12. 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
13. For Germany only: In the investigator’s opinion, the patient is not expected to survive ≥12 months.
14. 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.