Clinical trial NCT01226563: IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myocardial Infarction
Congestive Heart Failure
ST-Elevation Myocardial Infarction
Keywords: STEMI
Acute Myocardial Infarction
Congestive Heart Failure
Left Ventricular Remodeling
Devices, Medical
Lead sponsor: Bellerophon
Sponsor class: INDUSTRY
First posted: 2010-10-22
Enrollment: 303
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: PREVENTION

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).

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 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.

Primary outcomes:
measure: Left Ventricular End Diastolic Volume Index
timeFrame: Baseline, 6 Months
Secondary outcomes:
measure: Kansas City Cardiomyopathy Questionaire
timeFrame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits
measure: Six minute walk test
timeFrame: Baseline (prior to discharge STEMI), 1, 3, 6 and 12 month follow-up visits
measure: New York Heart Association (NYHA) functional classification (Physician reported)
timeFrame: Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits
measure: Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations
timeFrame: 5 Years
measure: Re-hospitalization due to any cardiovascular event
timeFrame: 5 Years
Other outcomes:
measure: NT-pro-brain natriuretic peptide (NT-proBNP) levels
timeFrame: Baseline, discharge, 1, 3, and 6 month follow-up visits.
measure: Short Form 12 (SF-12) Questionnaire
timeFrame: Baseline (prior to the index STEMI), 1, 3, 6 and 12 month follow-up visits
measure: Measurement of alginate in plasma and urine
timeFrame: Baseline, 5, 30 min, 1, 3, 8, 24, 48 hrs, 1, 3 month
measure: Healthcare utilization
timeFrame: 6 and 12 month follow-up visits.
measure: Anatomic endpoints
timeFrame: 4 to 6 hours following deployment, 1, 3 and 12 month follow-up visits
measure: Primary Safety Evaluation
timeFrame: 1 Year
measure: Long-term Safety Evaluation
timeFrame: 1 year to 5 years after device deployment
measure: Continuous Electrocardiogram Cardiac Safety Endpoints
timeFrame: Baseline, prior to discharge, 1, 3 and 6 month follow-up visits
measure: Clinical Chemistry, Hematology, and Urinalysis panel
timeFrame: Clinical Chemistry, Hematology: Baseline, 8 hours (± 2 hours) post-deployment, 1, 3, and 6 month follow-up visits. Urinalysis : Baseline and discharge
measure: Performance Goal and Study Success
timeFrame: Baseline to 6 months
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Torrance
country: United States
facility: Harbor - UCLA Medical Center
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Indianapolis
country: United States
facility: St. Vincent Medical Group Inc.
state: Indiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center Weiler Division
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
city: Greenville
country: United States
facility: East Carolina Heart Institute - ECHI
state: North Carolina
city: Cincinnati
country: United States
facility: Carl and Edyth Lindner Center for Research and Education @ Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Brisbane
city: Southport
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elisabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Northern Hospital
state: Victoria
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Perth
country: Australia
facility: Royal Perth Hospital - Dept. of Cardiology
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg (ZOL)
city: Liege
country: Belgium
facility: CHU du Sart Tilman
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Newmarket
country: Canada
facility: York PCI Research
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
city: Quebec
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
city: Brive la Gaillarde
country: France
facility: Hopital de Brive Service de Cardiologie
city: Creteil Cedex
country: France
facility: Hopital Henri Mondor
city: Dijon Cedex
country: France
facility: Hopital du Bocage Central
city: Grenoble Cedex 09
country: France
facility: CHU Grenoble - Hopital Michallon
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille
city: Nice Cedex 1
country: France
facility: Centre Hospitalier Universitaire de Nice Hopital Pasteur
city: Paris
country: France
facility: Hopital Lariboisiere
city: Strasbourg Cedex
country: France
facility: Nouvel Hopital Civil
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Rangueil
city: Berlin
country: Germany
facility: Vivantes Netzwerk fur Gesundheit GmbH, Kinikum Neukolln
city: Berlin
country: Germany
facility: Vivantes Humboldt-Klinikum
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitatsklinikum Jena, Klinik fur Innere Medizin, Kardiologie
city: Kiel
country: Germany
facility: Klinik fur Kardiologie and Angiologie Universitatsklinikum
city: Leipzig
country: Germany
facility: University of Leipzig
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: Mannheim
country: Germany
facility: Universitatsmedizin Mannheim
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen LMU
city: Neuss
country: Germany
facility: Stadtische Kliniken Neuss - Lukaskrankenhaus
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH
city: Siegen
country: Germany
facility: St. Marien-Krankenhaus Siegen gem. GMbH
city: Trier
country: Germany
facility: Krankenhaus Barmherzige Brüder Abt.Kardiologie und Pneumologie
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
city: Holon
country: Israel
facility: The Edith Wolfson Medical Center
state: Tel Aviv
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Haifa
country: Israel
facility: B'nai Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center Jerusalem-Cardiology
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center - Tel Hashomer
city: Gdańsk
country: Poland
facility: UCK, Kliniczne Centrum Kardiologii
city: Krakow
country: Poland
facility: Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kardiologii Interwencyjnej
city: Kraków
country: Poland
facility: I Klinika Kardiologii i Elektrokardiologii lnterwencyjnej oraz Nadcisnienia Tetniczego CM UJ
city: Lodz
country: Poland
facility: Oddzial Kardiologiczny Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi
city: Lublin
country: Poland
facility: Samodzileny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie
city: Warsaw
country: Poland
facility: Pracownia Kardiologii Inwazyjnej
city: Warszawa
country: Poland
facility: Cetrainy Szpital Kliniczny MSWIA
city: Barcelona
country: Spain
facility: Hospital del Mar/Passeig Maritim 25-29
city: Huelva
country: Spain
facility: Hospital Juan Ramon Jimenez
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santiago
country: Spain
facility: Hospital Clinico de Santiago de Compostela
Study officials:
affiliation: Bellerophon Therapeutics
name: Ashika Ahmed, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.