IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction (PRESERVATION-1)

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

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).

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure; Acute Myocardial Infarction; ST-Elevation Myocardial Infarction
• Intervention / Treatment: Device: IK-5001; Device: Saline Solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Perth, Australia, 6000
    • Royal Perth Hospital - Dept. of Cardiology
  • Brisbane
    • Woolloongabba, Brisbane, Australia, 4102
      • Princess Alexandra Hospital
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Gold Coast Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elisabeth Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3076
      • The Northern Hospital
• Belgium
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim
  • Brussel, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg (ZOL)
  • Liege, Belgium
    • CHU du Sart Tilman
• Canada
  • Montreal, Canada, QC H1T 1C8
    • Montreal Heart Institute
  • Quebec, Canada, 3840
    • Centre Hospitalier de l'Universite de Montreal (CHUM)
  • Quebec, Canada, J1H 5N4
    • Centre Hospitalier Universitaire de Sherbrooke
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandra Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II Health Science Centre
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 2P7
      • York PCI Research
    • Toronto, Ontario, Canada, M5B-1W8
      • St. Michael's Hospital
• France
  • Brive la Gaillarde, France, 19312
    • Hopital de Brive Service de Cardiologie
  • Creteil Cedex, France, 94010
    • Hôpital Henri Mondor
  • Dijon Cedex, France, 21079
    • Hôpital du Bocage Central
  • Grenoble Cedex 09, France
    • CHU Grenoble - Hôpital MICHALLON
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille
  • Nice Cedex 1, France, 06002
    • Centre Hospitalier Universitaire de Nice Hopital Pasteur
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Strasbourg Cedex, France, 67091
    • Nouvel Hôpital Civil
  • Toulouse, France, 31059
    • CHU de Toulouse - Hôpital Rangueil
• Germany
  • Berlin, Germany, 12351
    • Vivantes Netzwerk fur Gesundheit GmbH, Kinikum Neukolln
  • Berlin, Germany, 13509
    • Vivantes Humboldt-Klinikum
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Essen, Germany, 45138
    • Elisabeth-Krankenhaus
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
  • Jena, Germany, 07747
    • Universitatsklinikum Jena, Klinik fur Innere Medizin, Kardiologie
  • Kiel, Germany, 24105
    • Klinik fur Kardiologie and Angiologie Universitatsklinikum
  • Leipzig, Germany, D-04289
    • University of Leipzig
  • Lubeck, Germany, 23538
    • Universitatsklinikum Schleswig-Holstein
  • Ludwigshafen, Germany, D-67063
    • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • Mannheim, Germany, D-68167
    • Universitätsmedizin Mannheim
  • Munchen, Germany, 81377
    • Klinikum der Universität München LMU
  • Neuss, Germany, 41464
    • Städtische Kliniken Neuss - Lukaskrankenhaus
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg gGmbH
  • Siegen, Germany, 57072
    • St. Marien-Krankenhaus Siegen gem. GMbH
  • Trier, Germany, 54292
    • Krankenhaus Barmherzige Brüder Abt.Kardiologie und Pneumologie
  • Wuppertal, Germany, 42117
    • Helios Klinikum Wuppertal
• Israel
  • Afula, Israel, 18101
    • HaEmek Medical Center
  • Ashkelon, Israel, 78278
    • Barzilai Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 34362
    • The Lady Davis Carmel Medical Center
  • Haifa, Israel
    • B'nai Zion Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Medical Center Jerusalem-Cardiology
  • Rehovot, Israel
    • Kaplan Medical Center
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center - Tel Hashomer
  • Tel Aviv
    • Holon, Tel Aviv, Israel, 58100
      • The Edith Wolfson Medical Center
• Poland
  • Gdańsk, Poland, 80-952
    • UCK, Kliniczne Centrum Kardiologii
  • Krakow, Poland, 31-202
    • Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kardiologii Interwencyjnej
  • Kraków, Poland, 31-501
    • I Klinika Kardiologii i Elektrokardiologii lnterwencyjnej oraz Nadcisnienia Tetniczego CM UJ
  • Lodz, Poland, 91-347
    • Oddzial Kardiologiczny Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi
  • Lublin, Poland, 20-954
    • Samodzileny Publiczny Szpital Kliniczny nr 4 w Lublinie
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
  • Warsaw, Poland, 02-097
    • Pracownia Kardiologii Inwazyjnej
  • Warszawa, Poland, 02-507
    • Cetrainy Szpital Kliniczny MSWIA
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar/Passeig Maritim 25-29
  • Huelva, Spain, 21005
    • Hospital Juan Ramón Jimenez
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Santiago, Spain, 15706
    • Hospital Clínico de Santiago de Compostela
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology, P.C.
  • California
    • Torrance, California, United States, 90509
      • Harbor - UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Medical Group Inc.
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center Weiler Division
    • Stony Brook, New York, United States, 11794
      • Stony Brook Medicine
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina Heart Institute - ECHI
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Carl and Edyth Lindner Center for Research and Education @ Christ Hospital
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

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 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
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 thrombolysis in myocardial infarction (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.

Exclusion criteria:

Subjects will be excluded from participating in this trial if ANY of the following exclusion criteria are met:

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. See Appendix A for determining estimated creatinine clearance.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IK-5001; IK-5001 Sodium Alginate Calcium Gluconate intracoronary injection	Device: IK-5001; 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.; Other Names: Sodium Alginate Calcium Gluconate; BIOABSORBABLE CARDIAC MATRIX (BCM)
Placebo Comparator: Saline Solution; Saline Solution intracoronary injection	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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-pro-brain natriuretic peptide (NT-proBNP) levels	NT-pro-brain natriuretic peptide (NT-proBNP) levels	Baseline, discharge, 1, 3, and 6 month follow-up visits.
Short Form 12 (SF-12) Questionnaire	The SF-12 is a validated general quality of life self-administered instrument that has been used in various disease states.	Baseline (prior to the index STEMI), 1, 3, 6 and 12 month follow-up visits
Measurement of alginate in plasma and urine	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. Remaining sites: sparse sampling blood will be drawn at 1, 8 and 24 hours, 1 month and post-deployment.	Baseline, 5, 30 min, 1, 3, 8, 24, 48 hrs, 1, 3 month
Healthcare utilization	The healthcare utilization and questionnaire consists of subject responses to questions regarding mobility, self-care, usual activities, pain, discomfort, anxiety and depression.	6 and 12 month follow-up visits.
Anatomic endpoints	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.	4 to 6 hours following deployment, 1, 3 and 12 month follow-up visits
Primary Safety Evaluation	The following safety endpoints will be adjudicated by a Clinical Events Classification Committee: Death; Recurrent myocardial infarction (MI) or target vessel revascularization or stent thrombosis; Significant arrhythmia requiring therapy; Myocardial rupture	1 Year
Long-term Safety Evaluation	Death; Need for devices for the management of congestive heart failure (CHF)automated implantable cardiac defibrillator (AICD)cardiac resynchronization therapyleft ventricular assist device (LVAD); Heart transplant	1 year to 5 years after device deployment
Continuous Electrocardiogram Cardiac Safety Endpoints	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.	Baseline, prior to discharge, 1, 3 and 6 month follow-up visits
Clinical Chemistry, Hematology, and Urinalysis panel	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	Clinical Chemistry, Hematology: Baseline, 8 hours (± 2 hours) post-deployment, 1, 3, and 6 month follow-up visits. Urinalysis : Baseline and discharge
Performance Goal and Study Success	5 mL/m2 change or greater in LVEDVI in IK-5001 group vs. placebo	Baseline to 6 months

Collaborators and Investigators

• Sponsor: Bellerophon BCM LLC
• Investigators: Study Director: Ashika Ahmed, MD, Bellerophon Therapeutics

Publications and helpful links

General Publications

• Wei X, Chen S, Xie T, Chen H, Jin X, Yang J, Sahar S, Huang H, Zhu S, Liu N, Yu C, Zhu P, Wang W, Zhang W. An MMP-degradable and conductive hydrogel to stabilize HIF-1alpha for recovering cardiac functions. Theranostics. 2022 Jan 1;12(1):127-142. doi: 10.7150/thno.63481. eCollection 2022.
• Rao SV, Zeymer U, Douglas PS, Al-Khalidi H, White JA, Liu J, Levy H, Guetta V, Gibson CM, Tanguay JF, Vermeersch P, Roncalli J, Kasprzak JD, Henry TD, Frey N, Kracoff O, Traverse JH, Chew DP, Lopez-Sendon J, Heyrman R, Krucoff MW. Bioabsorbable Intracoronary Matrix for Prevention of Ventricular Remodeling After Myocardial Infarction. J Am Coll Cardiol. 2016 Aug 16;68(7):715-23. doi: 10.1016/j.jacc.2016.05.053.
• Frey N, Linke A, Suselbeck T, Muller-Ehmsen J, Vermeersch P, Schoors D, Rosenberg M, Bea F, Tuvia S, Leor J. Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study. Circ Cardiovasc Interv. 2014 Dec;7(6):806-12. doi: 10.1161/CIRCINTERVENTIONS.114.001478. Epub 2014 Oct 28.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 20, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimate): October 22, 2010

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; STEMI; Congestive Heart Failure; Left Ventricular Remodeling; Devices, Medical
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Heart Failure; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: IK-5001-VENREM-201

Plan for Individual participant data (IPD)

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