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

This study is currently recruiting participants.
Verified April 2014 by Bellerophon
Sponsor:
Information provided by (Responsible Party):
Bellerophon ( Bellerophon BCM, LLC )
ClinicalTrials.gov Identifier:
NCT01226563
First received: October 20, 2010
Last updated: April 2, 2014
Last verified: April 2014
  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 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


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.


  • 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:

    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: Up to 5 years after device deployment ] [ Designated as safety issue: Yes ]
    1. Death

      • If death: adjudicate for "cardiovascular" or "non-cardiovascular" or "cannot be determined"

    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 change or greater in LVEDVI in IK-5001 group vs. placebo


Estimated Enrollment: 306
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)
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01226563

Contacts
Contact: Diane Stebbins 908-238-6647 diane.stebbins@ikaria.com

  Show 79 Study Locations
Sponsors and Collaborators
Bellerophon BCM, LLC
Investigators
Study Director: Reinilde Heyrman, M.D. Bellerophon BCM, LLC
  More Information

No publications provided

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: April 2, 2014
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

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

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

ClinicalTrials.gov processed this record on April 22, 2014