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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bellerophon ( Bellerophon BCM LLC )
ClinicalTrials.gov Identifier:
NCT01226563
First received: October 20, 2010
Last updated: January 14, 2015
Last verified: January 2015
  Purpose

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).


Condition Intervention
Acute Myocardial Infarction
Congestive Heart Failure
ST-Elevation Myocardial Infarction
Device: Sodium Alginate and Calcium Gluconate
Device: Saline Solution

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Bellerophon:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 discharge 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: 5 Years ] [ 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: 5 Years ] [ Designated as safety issue: Yes ]
    Time to re-hospitalization due to any cardiovascular event


Other Outcome Measures:
  • 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.

    Remaining sites: sparse sampling blood will be drawn at 1, 8 and 24 hours, 1 month and post-deployment.


  • 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: 1 Year ] [ Designated as safety issue: Yes ]

    The following safety endpoints will be adjudicated by a Clinical Events Classification Committee:

    1. Death
    2. Recurrent myocardial infarction (MI) or target vessel revascularization or stent thrombosis
    3. Significant arrhythmia requiring therapy
    4. Myocardial rupture

  • Long-term Safety Evaluation [ Time Frame: 1 year to 5 years after device deployment ] [ Designated as safety issue: Yes ]
    1. Death
    2. Need for devices for the management of congestive heart failure (CHF)

      • automated implantable cardiac defibrillator (AICD)
      • cardiac resynchronization therapy
      • left ventricular assist device (LVAD)
    3. 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/m2 change or greater in LVEDVI in IK-5001 group vs. placebo


Estimated Enrollment: 306
Study Start Date: April 2012
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IK-5001
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.
Other Names:
  • IK-5001
  • BIOABSORBABLE CARDIAC MATRIX (BCM)
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01226563

  Hide Study Locations
Locations
United States, Alabama
Cardiology, P.C.
Birmingham, Alabama, United States, 35211
United States, California
Harbor - UCLA Medical Center
Torrance, California, United States, 90509
United States, District of Columbia
MedStar Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami Hospital
Miami, Florida, United States, 33136
United States, Indiana
St. Vincent Medical Group Inc.
Indianapolis, Indiana, United States, 46290
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Minneapolis Heart Institute
Minneapolis, Minnesota, United States, 55407
United States, New York
Montefiore Medical Center Weiler Division
Bronx, New York, United States, 10461
Stony Brook Medicine
Stony Brook, New York, United States, 11794
United States, North Carolina
East Carolina Heart Institute - ECHI
Greenville, North Carolina, United States, 27834
United States, Ohio
Carl and Edyth Lindner Center for Research and Education @ Christ Hospital
Cincinnati, Ohio, United States, 45219
Ohio Health Research Institute
Columbus, Ohio, United States, 43214
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Australia, Queensland
Gold Coast Hospital
Southport, Queensland, Australia, 4215
Princess Alexandra Hospital
Woolloongabba, Brisbane, Queensland, Australia, 4102
Australia, South Australia
The Queen Elisabeth Hospital
Woodville South, South Australia, Australia, 5011
Australia
Flinders Medical Centre
Bedford Park, Australia, 5042
Alfred Hospital
Melbourne, Victoria, Australia, 3004
The Northern Hospital
Melbourne, Victoria, Australia, 3076
Royal Perth Hospital - Dept. of Cardiology
Perth, Australia, 6000
Belgium
ZNA Middelheim
Antwerpen, Belgium, 2020
Universitair Ziekenhuis Brussel
Brussel, Belgium, 1090
Ziekenhuis Oost-Limburg (ZOL)
Genk, Belgium, 3600
CHU du Sart Tilman
Liege, Belgium
Canada, Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
Canada, Nova Scotia
Queen Elizabeth II Health Science Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
York PCI Research
Newmarket, Ontario, Canada, L3Y 2P7
Canada
Montreal Heart Institute
Montreal, Canada, QC H1T 1C8
Centre Hospitalier Universitaire de Sherbrooke
Quebec, Canada, J1H 5N4
Centre Hospitalier de l'Universite de Montreal (CHUM)
Quebec, Canada, 3840
St. Michael's Hospital
Toronto, Ontario, Canada, M5B-1W8
France
Hopital de Brive Service de Cardiologie
Brive la Gaillarde, France, 19312
Hopital Henri Mondor
Creteil Cedex, France, 94010
Hopital du Bocage Central
Dijon Cedex, France, 21079
CHU Grenoble - Hopital Michallon
Grenoble Cedex 09, France
Hopital Charles Nicolle
Haute Normandie, France, 7601
Centre Hospitalier Regional Universitaire de Lille
Lille, France, 59037
Centre Hospitalier Universitaire de Nice Hopital Pasteur
Nice Cedex 1, France, 06002
Hopital Lariboisiere
Paris, France, 75010
Nouvel Hopital Civil
Strasbourg Cedex, France, 67091
CHU de Toulouse - Hopital Rangueil
Toulouse, France, 31059
Germany
Vivantes Humboldt-Klinikum
Berlin, Germany, 13509
Vivantes Netzwerk fur Gesundheit GmbH, Kinikum Neukolln
Berlin, Germany, 12351
Helios Klinikum Erfurt
Erfurt, Germany, 99089
Elisabeth-Krankenhaus
Essen, Germany, 45138
Universitatsklinikum Heidelberg
Heidelberg, Germany, 69120
Universitatsklinikum Jena, Klinik fur Innere Medizin, Kardiologie
Jena, Germany, 07747
Klinik fur Kardiologie and Angiologie Universitatsklinikum
Kiel, Germany, 24105
University of Leipzig
Leipzig, Germany, D-04289
Universitatsklinikum Schleswig-Holstein
Lubeck, Germany, 23538
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
Ludwigshafen, Germany, D-67063
Universitatsmedizin Mannheim
Mannheim, Germany, D-68167
Klinikum der Universitat Munchen LMU
Munchen, Germany, 81377
Stadtische Kliniken Neuss - Lukaskrankenhaus
Neuss, Germany, 41464
Klinikum Oldenburg gGmbH
Oldenburg, Germany, 26133
St. Marien-Krankenhaus Siegen gem. GMbH
Siegen, Germany, 57072
Krankenhaus Barmherzige Brüder Abt.Kardiologie und Pneumologie
Trier, Germany, 54292
Helios Klinikum Wuppertal
Wuppertal, Germany, 42117
Israel
The Edith Wolfson Medical Center
Holon, Tel Aviv, Israel, 58100
HaEmek Medical Center
Afula, Israel, 18101
Barzilai Medical Center
Ashkelon, Israel, 78278
B'nai Zion Medical Center
Haifa, Israel
Rambam Medical Center
Haifa, Israel, 31096
The Lady Davis Carmel Medical Center
Haifa, Israel, 34362
Hadassah University Medical Center Jerusalem-Cardiology
Jerusalem, Israel, 91120
Kaplan Medical Center
Rehovot, Israel
Sheba Medical Center - Tel Hashomer
Tel Hashomer, Israel, 52621
Poland
UCK, Kliniczne Centrum Kardiologii
Gdnask, Poland, 80-952
Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kardiologii Interwencyjnej
Krakow, Poland, 31-202
I Klinika Kardiologii i Elektrokardiologii lnterwencyjnej oraz Nadcisnienia Tetniczego CM UJ
Kraków, Poland, 31-501
Oddzial Kardiologiczny Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi
Lodz, Poland, 91-347
Samodzileny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, Poland, 20-954
Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie
Szczecin, Poland, 70-111
Pracownia Kardiologii Inwazyjnej
Warsaw, Poland, 02-097
Cetrainy Szpital Kliniczny MSWIA
Warszawa, Poland, 02-507
Spain
Hospital del Mar/Passeig Maritim 25-29
Barcelona, Spain, 08003
Hospital Juan Ramon Jimenez
Huelva, Spain, 21005
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034
Hospital Clinico de Santiago de Compostela
Santiago, Spain, 15706
Sponsors and Collaborators
Bellerophon BCM LLC
Investigators
Study Director: Reinilde Heyrman, M.D. Bellerophon BCM LLC
  More Information

No publications provided by Bellerophon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bellerophon ( Bellerophon BCM LLC )
ClinicalTrials.gov Identifier: NCT01226563     History of Changes
Other Study ID Numbers: IK-5001-VENREM-201
Study First Received: October 20, 2010
Last Updated: January 14, 2015
Health Authority: Israel: Ministry of Health
United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Poland: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Bellerophon:
STEMI
Acute Myocardial Infarction
Congestive Heart Failure
Left Ventricular Remodeling
Devices, Medical

Additional relevant MeSH terms:
Heart Failure
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Alginic acid
Pharmaceutical Solutions
Coagulants
Hematologic Agents
Hemostatics
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2015