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

Sponsor

Bellerophon BCM LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01226563

Collaborator

(none)

303

Enrollment

Locations

Arms

Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	N/A

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.

Study Design

Study Type:

Interventional

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 placeboMulticenter, 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 :

Apr 1, 2012

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

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 BIOABSORBABLE CARDIAC MATRIX (BCM)
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.

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

BIOABSORBABLE CARDIAC MATRIX (BCM)

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Kansas City Cardiomyopathy Questionaire [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.
Six minute walk test [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
New York Heart Association (NYHA) functional classification (Physician reported) [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)
Cardiovascular death, non-fatal heart failure events or cardiovascular hospitalizations [5 Years]
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 [5 Years]
Time to re-hospitalization due to any cardiovascular event

Other Outcome Measures

NT-pro-brain natriuretic peptide (NT-proBNP) levels [Baseline, discharge, 1, 3, and 6 month follow-up visits.]
NT-pro-brain natriuretic peptide (NT-proBNP) levels
Short Form 12 (SF-12) Questionnaire [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.
Measurement of alginate in plasma and urine [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.
Healthcare utilization [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.
Anatomic endpoints [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.
Primary Safety Evaluation [1 Year]
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
Long-term Safety Evaluation [1 year to 5 years after device deployment]
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
Continuous Electrocardiogram Cardiac Safety Endpoints [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.
Clinical Chemistry, Hematology, and Urinalysis panel [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
Performance Goal and Study Success [Baseline to 6 months]
5 mL/m2 change or greater in LVEDVI in IK-5001 group vs. placebo

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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

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.
For Germany only: Patients determined to have Killip class 4 at time of device deployment are not eligible for randomization.
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:

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.
Need for urgent coronary artery bypass graft (CABG)
Clinically significant valvular heart disease with planned surgical correction or transcatheter aortic valve implantation (TAVI)
Uncontrolled ventricular arrhythmias
Renal insufficiency with a calculated creatinine clearance of less than 30 mL/ minute. See Appendix A for determining estimated creatinine clearance.
Clinically significant hepatic insufficiency
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
Non-ambulatory prior to the index MI
The subject has participated in another trial of an investigational agent within 30 days prior to randomization.
Subject has received resorbable stent as part of PCI.
The 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.
For Germany only: In the investigator's opinion, the patient is not expected to survive ≥12 months.
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

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Harbor - UCLA Medical Center	Torrance	California	United States	90509
3	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
4	University of Florida	Gainesville	Florida	United States	32610
5	University of Miami Hospital	Miami	Florida	United States	33136
6	St. Vincent Medical Group Inc.	Indianapolis	Indiana	United States	46290
7	Henry Ford Health System	Detroit	Michigan	United States	48202
8	Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
9	Montefiore Medical Center Weiler Division	Bronx	New York	United States	10461
10	Stony Brook Medicine	Stony Brook	New York	United States	11794
11	East Carolina Heart Institute - ECHI	Greenville	North Carolina	United States	27834
12	Carl and Edyth Lindner Center for Research and Education @ Christ Hospital	Cincinnati	Ohio	United States	45219
13	Ohio Health Research Institute	Columbus	Ohio	United States	43214
14	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
15	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
16	Rhode Island Hospital	Providence	Rhode Island	United States	02903
17	Princess Alexandra Hospital	Woolloongabba	Brisbane	Australia	4102
18	Gold Coast Hospital	Southport	Queensland	Australia	4215
19	The Queen Elisabeth Hospital	Woodville South	South Australia	Australia	5011
20	Alfred Hospital	Melbourne	Victoria	Australia	3004
21	The Northern Hospital	Melbourne	Victoria	Australia	3076
22	Flinders Medical Centre	Bedford Park		Australia	5042
23	Royal Perth Hospital - Dept. of Cardiology	Perth		Australia	6000
24	ZNA Middelheim	Antwerpen		Belgium	2020
25	Universitair Ziekenhuis Brussel	Brussel		Belgium	1090
26	Ziekenhuis Oost-Limburg (ZOL)	Genk		Belgium	3600
27	CHU du Sart Tilman	Liege		Belgium
28	Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
29	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia	Canada	B3H 3A7
30	York PCI Research	Newmarket	Ontario	Canada	L3Y 2P7
31	St. Michael's Hospital	Toronto	Ontario	Canada	M5B-1W8
32	Montreal Heart Institute	Montreal		Canada	QC H1T 1C8
33	Centre Hospitalier de l'Universite de Montreal (CHUM)	Quebec		Canada	3840
34	Centre Hospitalier Universitaire de Sherbrooke	Quebec		Canada	J1H 5N4
35	Hopital de Brive Service de Cardiologie	Brive la Gaillarde		France	19312
36	Hopital Henri Mondor	Creteil Cedex		France	94010
37	Hopital du Bocage Central	Dijon Cedex		France	21079
38	CHU Grenoble - Hopital Michallon	Grenoble Cedex 09		France
39	Centre Hospitalier Regional Universitaire de Lille	Lille		France	59037
40	Centre Hospitalier Universitaire de Nice Hopital Pasteur	Nice Cedex 1		France	06002
41	Hopital Lariboisiere	Paris		France	75010
42	Nouvel Hopital Civil	Strasbourg Cedex		France	67091
43	CHU de Toulouse - Hopital Rangueil	Toulouse		France	31059
44	Vivantes Netzwerk fur Gesundheit GmbH, Kinikum Neukolln	Berlin		Germany	12351
45	Vivantes Humboldt-Klinikum	Berlin		Germany	13509
46	Helios Klinikum Erfurt	Erfurt		Germany	99089
47	Elisabeth-Krankenhaus	Essen		Germany	45138
48	Universitatsklinikum Heidelberg	Heidelberg		Germany	69120
49	Universitatsklinikum Jena, Klinik fur Innere Medizin, Kardiologie	Jena		Germany	07747
50	Klinik fur Kardiologie and Angiologie Universitatsklinikum	Kiel		Germany	24105
51	University of Leipzig	Leipzig		Germany	D-04289
52	Universitatsklinikum Schleswig-Holstein	Lubeck		Germany	23538
53	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen		Germany	D-67063
54	Universitatsmedizin Mannheim	Mannheim		Germany	D-68167
55	Klinikum der Universitat Munchen LMU	Munchen		Germany	81377
56	Stadtische Kliniken Neuss - Lukaskrankenhaus	Neuss		Germany	41464
57	Klinikum Oldenburg gGmbH	Oldenburg		Germany	26133
58	St. Marien-Krankenhaus Siegen gem. GMbH	Siegen		Germany	57072
59	Krankenhaus Barmherzige Brüder Abt.Kardiologie und Pneumologie	Trier		Germany	54292
60	Helios Klinikum Wuppertal	Wuppertal		Germany	42117
61	The Edith Wolfson Medical Center	Holon	Tel Aviv	Israel	58100
62	HaEmek Medical Center	Afula		Israel	18101
63	Barzilai Medical Center	Ashkelon		Israel	78278
64	Rambam Medical Center	Haifa		Israel	31096
65	The Lady Davis Carmel Medical Center	Haifa		Israel	34362
66	B'nai Zion Medical Center	Haifa		Israel
67	Hadassah University Medical Center Jerusalem-Cardiology	Jerusalem		Israel	91120
68	Kaplan Medical Center	Rehovot		Israel
69	Sheba Medical Center - Tel Hashomer	Tel Hashomer		Israel	52621
70	UCK, Kliniczne Centrum Kardiologii	Gdańsk		Poland	80-952
71	Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kardiologii Interwencyjnej	Krakow		Poland	31-202
72	I Klinika Kardiologii i Elektrokardiologii lnterwencyjnej oraz Nadcisnienia Tetniczego CM UJ	Kraków		Poland	31-501
73	Oddzial Kardiologiczny Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi	Lodz		Poland	91-347
74	Samodzileny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin		Poland	20-954
75	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie	Szczecin		Poland	70-111
76	Pracownia Kardiologii Inwazyjnej	Warsaw		Poland	02-097
77	Cetrainy Szpital Kliniczny MSWIA	Warszawa		Poland	02-507
78	Hospital del Mar/Passeig Maritim 25-29	Barcelona		Spain	08003
79	Hospital Juan Ramon Jimenez	Huelva		Spain	21005
80	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
81	Hospital Universitario La Paz	Madrid		Spain	28046
82	Hospital Clinico de Santiago de Compostela	Santiago		Spain	15706