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

Acute Myocardial Infarction Clinical Trial

— PRESERVATION-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01226563
• Other study ID #: IK-5001-VENREM-201
• Status: Completed
• Phase: N/A
• Start date: April 2012
• Est. completion date: December 2015

Study information

• Verified date: July 2018
• Source: Bellerophon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: December 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Congestive Heart Failure
• Heart Failure
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• ST-Elevation Myocardial Infarction

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Alfred Hospital	Melbourne	Victoria
Australia	The Northern Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital - Dept. of Cardiology	Perth
Australia	Gold Coast Hospital	Southport	Queensland
Australia	The Queen Elisabeth Hospital	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Brisbane
Belgium	ZNA Middelheim	Antwerpen
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Ziekenhuis Oost-Limburg (ZOL)	Genk
Belgium	CHU du Sart Tilman	Liege
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	Montreal Heart Institute	Montreal
Canada	York PCI Research	Newmarket	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
France	Hopital de Brive Service de Cardiologie	Brive la Gaillarde
France	Hopital Henri Mondor	Creteil Cedex
France	Hopital du Bocage Central	Dijon Cedex
France	CHU Grenoble - Hopital Michallon	Grenoble Cedex 09
France	Centre Hospitalier Regional Universitaire de Lille	Lille
France	Centre Hospitalier Universitaire de Nice Hopital Pasteur	Nice Cedex 1
France	Hopital Lariboisiere	Paris
France	Nouvel Hopital Civil	Strasbourg Cedex
France	CHU de Toulouse - Hopital Rangueil	Toulouse
Germany	Vivantes Humboldt-Klinikum	Berlin
Germany	Vivantes Netzwerk fur Gesundheit GmbH, Kinikum Neukolln	Berlin
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Elisabeth-Krankenhaus	Essen
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Jena, Klinik fur Innere Medizin, Kardiologie	Jena
Germany	Klinik fur Kardiologie and Angiologie Universitatsklinikum	Kiel
Germany	University of Leipzig	Leipzig
Germany	Universitatsklinikum Schleswig-Holstein	Lubeck
Germany	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen
Germany	Universitatsmedizin Mannheim	Mannheim
Germany	Klinikum der Universitat Munchen LMU	Munchen
Germany	Stadtische Kliniken Neuss - Lukaskrankenhaus	Neuss
Germany	Klinikum Oldenburg gGmbH	Oldenburg
Germany	St. Marien-Krankenhaus Siegen gem. GMbH	Siegen
Germany	Krankenhaus Barmherzige Brüder Abt.Kardiologie und Pneumologie	Trier
Germany	Helios Klinikum Wuppertal	Wuppertal
Israel	HaEmek Medical Center	Afula
Israel	Barzilai Medical Center	Ashkelon
Israel	B'nai Zion Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	The Lady Davis Carmel Medical Center	Haifa
Israel	The Edith Wolfson Medical Center	Holon	Tel Aviv
Israel	Hadassah University Medical Center Jerusalem-Cardiology	Jerusalem
Israel	Kaplan Medical Center	Rehovot
Israel	Sheba Medical Center - Tel Hashomer	Tel Hashomer
Poland	UCK, Kliniczne Centrum Kardiologii	Gdansk
Poland	Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kardiologii Interwencyjnej	Krakow
Poland	I Klinika Kardiologii i Elektrokardiologii lnterwencyjnej oraz Nadcisnienia Tetniczego CM UJ	Kraków
Poland	Oddzial Kardiologiczny Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi	Lodz
Poland	Samodzileny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin
Poland	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie	Szczecin
Poland	Pracownia Kardiologii Inwazyjnej	Warsaw
Poland	Cetrainy Szpital Kliniczny MSWIA	Warszawa
Spain	Hospital del Mar/Passeig Maritim 25-29	Barcelona
Spain	Hospital Juan Ramon Jimenez	Huelva
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Clinico de Santiago de Compostela	Santiago
United States	Cardiology, P.C.	Birmingham	Alabama
United States	Montefiore Medical Center Weiler Division	Bronx	New York
United States	Carl and Edyth Lindner Center for Research and Education @ Christ Hospital	Cincinnati	Ohio
United States	Ohio Health Research Institute	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	East Carolina Heart Institute - ECHI	Greenville	North Carolina
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	St. Vincent Medical Group Inc.	Indianapolis	Indiana
United States	University of Miami Hospital	Miami	Florida
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Stony Brook Medicine	Stony Brook	New York
United States	Harbor - UCLA Medical Center	Torrance	California
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bellerophon BCM LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	NT-pro-brain natriuretic peptide (NT-proBNP) levels	NT-pro-brain natriuretic peptide (NT-proBNP) levels	Baseline, discharge, 1, 3, and 6 month follow-up visits.
Other	Short Form 12 (SF-12) Questionnaire	The SF-12 is a validated general quality of life self-administered instrument that has been used in various disease states.	Baseline (prior to the index STEMI), 1, 3, 6 and 12 month follow-up visits
Other	Measurement of alginate in plasma and urine	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.	Baseline, 5, 30 min, 1, 3, 8, 24, 48 hrs, 1, 3 month
Other	Healthcare utilization	The healthcare utilization and questionnaire consists of subject responses to questions regarding mobility, self-care, usual activities, pain, discomfort, anxiety and depression.	6 and 12 month follow-up visits.
Other	Anatomic endpoints	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.	4 to 6 hours following deployment, 1, 3 and 12 month follow-up visits
Other	Primary Safety Evaluation	The following safety endpoints will be adjudicated by a Clinical Events Classification Committee: Death; Recurrent myocardial infarction (MI) or target vessel revascularization or stent thrombosis; Significant arrhythmia requiring therapy; Myocardial rupture	1 Year
Other	Long-term Safety Evaluation	Death; Need for devices for the management of congestive heart failure (CHF); automated implantable cardiac defibrillator (AICD); cardiac resynchronization therapy; left ventricular assist device (LVAD); Heart transplant	1 year to 5 years after device deployment
Other	Continuous Electrocardiogram Cardiac Safety Endpoints	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.	Baseline, prior to discharge, 1, 3 and 6 month follow-up visits
Other	Clinical Chemistry, Hematology, and Urinalysis panel	Chemistry panel - levels of albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, calcium, serum chloride, bicarbonate, direct bilirubin, creatinine, ?-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	Clinical Chemistry, Hematology: Baseline, 8 hours (± 2 hours) post-deployment, 1, 3, and 6 month follow-up visits. Urinalysis : Baseline and discharge
Other	Performance Goal and Study Success	5 mL/m2 change or greater in LVEDVI in IK-5001 group vs. placebo	Baseline to 6 months
Primary	Left Ventricular End Diastolic Volume Index	Anatomic measurement of left ventricular end diastolic volume index (LVEDVI) assessed through echocardiogram.	Baseline, 6 Months
Secondary	Kansas City Cardiomyopathy Questionaire	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.	Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits
Secondary	Six minute walk test	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	Baseline (prior to discharge STEMI), 1, 3, 6 and 12 month follow-up visits
Secondary	New York Heart Association (NYHA) functional classification (Physician reported)	New York Heart Association (NYHA) classification assessed by physician will be categorized by Class (Class I - IV)	Baseline (prior to index STEMI), 1, 3, 6 and 12 month follow-up visits
Secondary	Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations	Time to cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations adjudicated by a Clinical Events Committee	5 Years
Secondary	Re-hospitalization due to any cardiovascular event	Time to re-hospitalization due to any cardiovascular event	5 Years