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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01226563
Recruitment Status : Completed
First Posted : October 22, 2010
Last Update Posted : August 11, 2022
Information provided by (Responsible Party):
Bellerophon ( Bellerophon BCM LLC )

Brief Summary:
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 or disease Intervention/treatment Phase
Acute Myocardial Infarction Congestive Heart Failure ST-Elevation Myocardial Infarction Device: IK-5001 Device: Saline Solution Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 303 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effects of IK-5001. 306 trials randomized 2:1 active vs placebo
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: randomized 2:1 active vs placebo
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
Study Start Date : April 2012
Actual Primary Completion Date : August 2015
Actual Study Completion Date : December 2015

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

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.

Primary Outcome Measures :
  1. Left Ventricular End Diastolic Volume Index [ Time Frame: Baseline, 6 Months ]
    Anatomic measurement of left ventricular end diastolic volume index (LVEDVI) assessed through echocardiogram.

Secondary Outcome Measures :
  1. Kansas City Cardiomyopathy Questionaire [ Time Frame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits ]
    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.

  2. Six minute walk test [ Time Frame: Baseline (prior to discharge STEMI), 1, 3, 6 and 12 month follow-up visits ]
    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

  3. 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 ]
    New York Heart Association (NYHA) classification assessed by physician will be categorized by Class (Class I - IV)

  4. Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations [ Time Frame: 5 Years ]
    Time to cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations adjudicated by a Clinical Events Committee

  5. Re-hospitalization due to any cardiovascular event [ Time Frame: 5 Years ]
    Time to re-hospitalization due to any cardiovascular event

Other Outcome Measures:
  1. NT-pro-brain natriuretic peptide (NT-proBNP) levels [ Time Frame: Baseline, discharge, 1, 3, and 6 month follow-up visits. ]
    NT-pro-brain natriuretic peptide (NT-proBNP) levels

  2. Short Form 12 (SF-12) Questionnaire [ Time Frame: Baseline (prior to the index STEMI), 1, 3, 6 and 12 month follow-up visits ]
    The SF-12 is a validated general quality of life self-administered instrument that has been used in various disease states.

  3. Measurement of alginate in plasma and urine [ Time Frame: Baseline, 5, 30 min, 1, 3, 8, 24, 48 hrs, 1, 3 month ]

    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.

  4. Healthcare utilization [ Time Frame: 6 and 12 month follow-up visits. ]
    The healthcare utilization and questionnaire consists of subject responses to questions regarding mobility, self-care, usual activities, pain, discomfort, anxiety and depression.

  5. Anatomic endpoints [ Time Frame: 4 to 6 hours following deployment, 1, 3 and 12 month follow-up visits ]
    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.

  6. Primary Safety Evaluation [ Time Frame: 1 Year ]

    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

  7. Long-term Safety Evaluation [ Time Frame: 1 year to 5 years after device deployment ]
    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

  8. Continuous Electrocardiogram Cardiac Safety Endpoints [ Time Frame: Baseline, prior to discharge, 1, 3 and 6 month follow-up visits ]
    • 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.

  9. 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 ]

    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

  10. Performance Goal and Study Success [ Time Frame: Baseline to 6 months ]
    5 mL/m2 change or greater in LVEDVI in IK-5001 group vs. placebo

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01226563

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Sponsors and Collaborators
Bellerophon BCM LLC
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Study Director: Ed Parsley, DO Bellerophon Therapeutics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bellerophon BCM LLC
ClinicalTrials.gov Identifier: NCT01226563    
Other Study ID Numbers: IK-5001-VENREM-201
First Posted: October 22, 2010    Key Record Dates
Last Update Posted: August 11, 2022
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Bellerophon ( Bellerophon BCM LLC ):
Acute Myocardial Infarction
Congestive Heart Failure
Left Ventricular Remodeling
Devices, Medical
Additional relevant MeSH terms:
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Heart Failure
Myocardial Infarction
ST Elevation Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Myocardial Ischemia
Vascular Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs