IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction - Full Text View

Sponsor:	Ikaria Holdings Inc.
Information provided by (Responsible Party):	Ikaria Holdings Inc.
ClinicalTrials.gov Identifier:	NCT01226563

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	Phase
Acute Myocardial Infarction Congestive Heart Failure ST-Elevation Myocardial Infarction	Device: Sodium Alginate and Calcium Gluconate Device: Saline Solution	Phase 2

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:

MedlinePlus related topics: Calcium Heart Attack Heart Failure

Drug Information available for: Calcium Gluconate Manganese gluconate

U.S. FDA Resources

Further study details as provided by Ikaria Holdings Inc.:

Primary Outcome Measures:

Left ventricular end diastolic volume index [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
Anatomic measurement of left ventricular end diastolic volume index will be assessed through echocardiogram.
Kansas City Cardiomyopathy Questionaire score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The Kansas City Cardiomyopathy Questionaire (KCCQ) score is 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: 6 months ] [ Designated as safety issue: No ]
The six minute walk test (6MWT) will be performed and used to measure response to treatment in subjects with moderate to severe heart disease

Secondary Outcome Measures:

New York Heart Association classification [ Time Frame: 12 months ] [ Designated as safety issue: No ]
New York Heart Association (NYHA) classification assessed by physician will be categorized by Class (Class I - IV)
NT-pro-brain natriuretic peptide (NT-proBNP) levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
NT-pro-BNP levels will be measured through blood draws.
Cardiovascular death and non-fatal heart failure events [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
CV death or non-fatal heart failure events; time to first re-hospitalization due to CV event
Measurement of alginate in plasma and urine [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Measurement of alginate in plasma and urine will be assessed through hematology and urinalysis
Clinical chemistry panel [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Chemistry panel (collected at baseline, 8 hours (± 2 hours) post-deployment will include levels of albumin, alkaline phosphatase, ALT, AST, blood urea nitrogen, calcium, serum chloride, bicarbonate, direct bilirubin, creatinine, γ-GT, glucose, lactate dehydrogenase, potassium, sodium, and total bilirubin.
Healthcare Utilization and Questionaire [ Time Frame: 6 months and 12 months ] [ 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.

Estimated Enrollment:	306
Study Start Date:	December 2011
Estimated Study Completion Date:	November 2013
Estimated Primary Completion Date:	November 2012 (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 slow bolus, intracoronary injection of IK-5001 will be administered over 15 to 30 seconds	Device: Sodium Alginate and Calcium Gluconate 4 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 Name: IK-5001
Placebo Comparator: Saline Solution A 4 mL slow bolus intracoronary injection of saline solution will be administered over 15 to 30 seconds	Device: Saline Solution 4 mL slow bolus, intracoronary injection of saline solution will be administered over 15 to 30 seconds at least 2 days after 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:

The subject is ≥ 18 years of age
The subject has given informed consent
The subject has experienced a large ST segment elevation MI defined by the following criteria:

a. 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 3 of the following 5 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
- 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% at baseline echocardiogram with wall motion abnormality in the appropriate distribution
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 TIMI 2 flow. Subjects undergoing rescue PCI after thrombolysis or delayed presentation with ongoing ischemia may be enrolled.

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

Any subject with cardiogenic shock requiring mechanical ventilation or mechanical support at the time of deployment. Transient need for mechanical ventilation or circulatory support will not exclude a subject.
Need for urgent coronary artery bypass graft (CABG)
Clinically significant valvular heart disease with planned surgical correction
History of CHF prior to MI
Uncontrolled ventricular arrhythmias
Renal insufficiency with a calculated creatinine clearance of less than 30 mL/ minute)
Renal insufficiency with a calculated creatinine clearance of less than 60 mL/ minute)(FOR ISRAEL ONLY)
Clinically significant hepatic insufficiency
Inadequate imaging windows (defined as the inability to visualize the endocardial border all 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
Non-ambulatory prior to the index MI
Subject has participated in another investigational trial within 30 days prior to randomization
Subject has received resorbable stent as part of PCI
Subject is pregnant or breastfeeding. Women of child-bearing potential will have a negative urine pregnancy test prior to randomization
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.
Subject has a history of diabetes mellitus (FOR ISRAEL ONLY)

Contacts and Locations

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

Contacts

Contact: Catherine Pelc

908-238-6636

catherine.pelc@ikaria.com

Locations

Australia
Flinders Medical Centre	Recruiting
Bedford Park, Australia, 5042
Principal Investigator: Derek Chew, MD
Alfred Hospital	Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Susie Cartledge +61-3-9076-2902 scartledge@alfred.org.au
Principal Investigator: Henry Krum, MD
The Northern Hospital	Recruiting
Melbourne, Victoria, Australia, 3076
Contact: Mary Park 61-3-8405-8996 Mary.park@nh.org.au
Principal Investigator: William vanGaal, MD
Israel
Barzilai Medical Center	Recruiting
Ashkelon, Israel, 78278
Contact: Irena Greenshtein 972-8-6745870 irenag@barzi.health.gov.il
Principal Investigator: Amos Katz, MD
B'nai Zion Medical Center	Recruiting
Haifa, Israel
Contact: Smader Harel 972-526060524 Smader.harel@b-zion.org.il
Principal Investigator: Uri Rosenschein, MD
Kaplan Medical Center	Recruiting
Rehovot, Israel
Contact: Suzi Trepp 972-8-9441069 suzitr@clalit.org.il
Contact: Nina Roitberg 972-8-8609567 ninaro@clalit.org.il
Principal Investigator: Oscar Kracoff, MD

Sponsors and Collaborators

Ikaria Holdings Inc.

Investigators

Study Director:

James Baldassarre, MD

Ikaria Holdings Inc.

More Information

No publications provided

Responsible Party:	Ikaria Holdings Inc.
ClinicalTrials.gov Identifier:	NCT01226563 History of Changes
Other Study ID Numbers:	IK-5001-VENREM-201
Study First Received:	October 20, 2010
Last Updated:	May 16, 2012
Health Authority:	Australia: Human Research Ethics Committee Israel: Ministry of Health United States: Food and Drug Administration

Keywords provided by Ikaria Holdings Inc.:

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 May 24, 2012