IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction (PRESERVATION 1)
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).
Acute Myocardial Infarction
Congestive Heart Failure
ST-Elevation Myocardial Infarction
Device: Sodium Alginate and Calcium Gluconate
Device: Saline Solution
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
|Official Title:||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 - Preservation I Trial|
- Left Ventricular End Diastolic Volume Index [ Time Frame: Baseline, 6 Months ] [ Designated as safety issue: No ]Anatomic measurement of left ventricular end diastolic volume index (LVEDVI) assessed through echocardiogram.
- Kansas City Cardiomyopathy Questionaire [ Time Frame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits ] [ Designated as safety issue: No ]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.
- Six minute walk test [ Time Frame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits ] [ Designated as safety issue: No ]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
- New York Heart Association (NYHA) functional classification (Physician reported) [ Time Frame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits ] [ Designated as safety issue: Yes ]New York Heart Association (NYHA) classification assessed by physician will be categorized by Class (Class I - IV)
- Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]Time to cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations adjudicated by a Clinical Events Committee
- Re-hospitalization due to any cardiovascular event [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]Time to re-hospitalization due to any cardiovascular event
- NT-pro-brain natriuretic peptide (NT-proBNP) levels [ Time Frame: Baseline, discharge, 1, 3, and 6 month follow-up visits. ] [ Designated as safety issue: No ]NT-pro-brain natriuretic peptide (NT-proBNP) levels
- Short Form 12 (SF-12) Questionnaire [ Time Frame: Baseline (prior to the index STEMI), 1, 3, 6 and 12 month follow-up visits ] [ Designated as safety issue: No ]The SF-12 is a validated general quality of life self-administered instrument that has been used in various disease states.
- Measurement of alginate in plasma and urine [ Time Frame: Baseline, 5, 30 min, 1, 3, 8, 24, 48 hrs, 1, 3 month ] [ Designated as safety issue: No ]
At selected sites, relatively intensive sampling: blood will be drawn just prior to deployment (0 hour), 5 and 30 minutes and 1, 3, 8, 24, 48 hrs post deployment or until discharge, whichever occurs first, and at 1 and 3 month follow-up visit.
At selected sites, urine collection for measurements of alginate, 4 urine samples, will be collected at baseline (within 30 min prior to deployment), 0-8 hrs (from the time immediately following the device deployment through 8 hrs post deployment), 8 through 24 hours through post deployment, 24 through 48 hrs or discharge (whichever comes first). In addition, a urine sample will be taken at 1 and 3 month follow-up visits.
- Healthcare utilization [ Time Frame: 6 and 12 month follow-up visits. ] [ Designated as safety issue: No ]The healthcare utilization and questionnaire consists of subject responses to questions regarding mobility, self-care, usual activities, pain, discomfort, anxiety and depression.
- Anatomic endpoints [ Time Frame: 4 to 6 hours following deployment, 1, 3 and 12 month follow-up visits ] [ Designated as safety issue: No ]Anatomic endpoints: ejection fraction, end systolic volume index, mitral regurgitation, diastolic function, sphericity index, wall thickness, wall motion score and left ventricular (LV) mass index derived from the echocardiogram.
- Primary Safety Evaluation [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
The following safety endpoints will be adjudicated by a Clinical Events Classification Committee:
- Recurrent myocardial infarction (MI) or target vessel revascularization or stent thrombosis
- Significant arrhythmia requiring therapy
- Myocardial rupture
- Long-term Safety Evaluation [ Time Frame: Up to 5 years after device deployment ] [ Designated as safety issue: Yes ]
• If death: adjudicate for "cardiovascular" or "non-cardiovascular" or "cannot be determined"
Need for devices for the management of congestive heart failure (CHF)
- automated implantable cardiac defibrillator (AICD)
- cardiac resynchronization therapy
- left ventricular assist device (LVAD)
- Heart transplant
- Continuous Electrocardiogram Cardiac Safety Endpoints [ Time Frame: Baseline, prior to discharge, 1, 3 and 6 month follow-up visits ] [ Designated as safety issue: Yes ]
- New ischemia by ST segment deviation
- QT/QTcF (Fridericia's heart rate correction) before and 18 hours after procedure
- Severe bradycardia or tachycardia, including sustained ventricular or supraventricular tachycardia, total beats in episodes of tachycardia, total pauses and newly paced beats.
- Clinical Chemistry, Hematology, and Urinalysis panel [ Time Frame: Clinical Chemistry, Hematology: Baseline, 8 hours (± 2 hours) post-deployment, 1, 3, and 6 month follow-up visits. Urinalysis : Baseline and discharge ] [ Designated as safety issue: Yes ]
Chemistry panel - levels of albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, calcium, serum chloride, bicarbonate, direct bilirubin, creatinine, γ-GT, glucose, lactate dehydrogenase, potassium, sodium, and total bilirubin.
Hematology panel - hemoglobin, hematocrit, mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell (WBC) levels (with 5 part differential), and platelet count.
Urinalysis - pH, specific gravity, RBC, WBC, glucose, protein in the urine, and a Human chorionic gonadotropin (HCG) pregnancy test
- Performance Goal and Study Success [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]5 mL change or greater in LVEDVI in IK-5001 group vs. placebo
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||July 2019|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
IK-5001 is a aqueous mixture of sodium alginate and calcium gluconate. A 4 mL (+/- 0.2 mL)slow bolus, intracoronary injection of IK-5001 will be administered over 30 to 60 seconds
Device: Sodium Alginate and Calcium Gluconate
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.
Placebo Comparator: Saline Solution
A 4 mL (+/- 0.2 mL)slow bolus intracoronary injection of saline solution will be administered over 30 to 60 seconds
Device: Saline Solution
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.
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.