Bone marrow transfer to enhance ST-elevation infarct regeneration-2

ISRCTN	ISRCTN17457407
DOI	https://doi.org/10.1186/ISRCTN17457407
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	2005-000774-46
Protocol serial number	Nil known
Sponsor	Individual Sponsor (Germany)
Funder	German Research Foundation (Deutsche Forschungsgemeinschaft) (ref: DR 148/13-1)

Submission date: 06/10/2005
Registration date: 04/11/2005
Last edited: 29/05/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Kai Wollert
Scientific

Department of Cardiology and Angiology
Hannover Medical School
Carl-Neuberg Str. 1
Hannover
30625
Germany

Phone	+49 (0)511 5324055
Email	wollert.kai@mh-hannover.de

Study information

Primary study design	Interventional
Study design	Randomized-controlled double-blind multicenter clinical trial
Secondary study design	Randomised controlled trial
Scientific title	BOne marrOw transfer to enhance ST-elevation infarct regeneration-2 (BOOST-2)
Study acronym	BOOST-2
Study objectives	BOOST-2 examines three principle hypotheses: 1st hypothesis: An intracoronary infusion of high-dose, non-irradiated Bone Marrow Cells (BMCs) is superior to an intracoronary infusion of control cells 2nd set of hypotheses: 1. An intracoronary infusion of high-dose BMCs (irradiated and non-irradiated) is superior to an intracoronary infusion of control cells 2. An intracoronary infusion of low-dose BMCs (irradiated and non-irradiated) is superior to an intracoronary infusion of control cells 3. Low-dose BMC-transfer (irradiated and non-irradiated) is not inferior to high-dose BMC-transfer (irradiated and non-irradiated) 3rd set of hypotheses: 1. An intracoronary infusion of non-irradiated BMCs (low-dose and high-dose) is superior to an intracoronary infusion of control cells 2. An intracoronary infusion of irradiated BMCs (low-dose and high-dose) is superior to an intracoronary infusion of control cells 3. Irradiated BMC-transfer (low-dose and high-dose) is not inferior to non-irradiated BMC-transfer (low-dose and high-dose)
Ethics approval(s)	Added as of 03/08/2007: The final study protocol (version 7), has been approved by the Ethics Committee of Hannover Medical School in Hannover, Germany on 03/02/2006 (No. 3812M)
Health condition(s) or problem(s) studied	Acute ST-Elevation Myocardial Infarction (STEMI)
Intervention	BOOST-2 is a randomized-controlled, double-blind, multicenter clinical trial investigating the effects of intracoronary nucleated BMC-transfer in patients after Acute Myocardial Infarction (AMI). BOOST-2 will investigate whether intracoronary BMC-transfer will have an effect on Left Ventricular (LV) functional and structural regeneration and have an impact on clinical endpoints as compared to a placebo cell infusion (erythrocytes only). BOOST-2 will address a number of biological and procedural issues. Irradiation of BMCs will be performed in two groups of patients just prior to intracoronary transfer. This study arm will reveal whether replication-competent cells (non-irradiated cells) are required for regeneration after AMI. In addition, BOOST-2 will address the question whether dose matters in BMC-therapy for AMI. BOOST-2 has six groups of patients: 1. Low dose, placebo cell infusion (20 patients) 2. High dose, placebo cell infusion (20 patients) 3. Low dose, non-irradiated BMC infusion (40 patients) 4. High dose, non-irradiated BMC infusion (40 patients) 5. Low dose, irradiated BMC infusion (40 patients) 6. High dose, irradiated BMC infusion (40 patients)
Intervention type	Biological/Vaccine
Phase	Not Applicable
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	Change in LV Ejection Fraction (LVEF) from baseline to 6 months follow-up (assessed by MRI). The primary endpoint will be analyzed separately in four subgroups: 1. Patients with a baseline LVEF smaller/larger than the median of the study population (assessed by MRI) 2. Patients undergoing PCI/stenting earlier/later than the median in the study population 3. Patients with an infarct size smaller/larger than the median of the study population (assessed by late contrast enhancement MRI) 4. Patients with a functional regenerative capacity of the infused bone marrow cells smaller/larger than the median of the study population Additional subgroups will be analyzed in an exploratory manner.
Key secondary outcome measure(s)	1. Change in LVEF from baseline to 18 months follow-up (assessed by MRI) 2. Changes in LV end-diastolic volume index, LV end-systolic volume index, infarct size (late enhancement), regional LV function, and myocardial perfusion from baseline to 6 and 18 months follow-up (assessed by MRI) 3. Changes in LV diastolic function from baseline to 6 and 18 months follow-up (echocardiography) 4. Exercise capacity at 6 and 18 months follow-up (cardiopulmonary exercise testing) 5. Quality of life (Minnesota Living with Heart Failure Questionnaire) and New York Heart Association (NYHA) class at 6 and 18 months follow-up 6. Combined clinical endpoint of death and hospitalization with heart failure
Completion date	01/01/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	200
Total final enrolment	153
Key inclusion criteria	Inclusion criteria amended as of 03/08/2007: The following is the new definition of inclusion criteria that has been effective since July 4th, 2007: 1. Age 30 years or older 2. First time STEMI 3. Time from symptom onset to reperfusion of >3 hours and baseline LV ejection fraction <57% as assessed by Magnetic Resonance Imaging (MRI) OR time from symptom onset to reperfusion between 1.5 and 3 hours and baseline LV ejection fraction <52% as assessed by MRI 4. Successful Percutaneous Coronary Intervention (PCI) and stent implantation of the infarct vessel (TIMI 2 or 3) 5. Severe hypokinesia or akinesia of >2/3 of the Left Ventricular (LV) anteroseptal, lateral, and/or inferior wall, as shown by LV angiography immediately after PCI/Stent 6. No previous infarction (late enhancement) in another territory as assessed by MRI 7.Written informed consent Inclusion criteria provided at time of registration: 1. Age 30 years or older 2. First time STEMI 3. Time from symptom onset to reperfusion of >3 hours 4. Successful Percutaneous Coronary Intervention (PCI) and stent implantation of the infarct vessel (TIMI 2 or 3) 5. Severe hypokinesia or akinesia of >2/3 of the Left Ventricular (LV) anteroseptal, lateral, and/or inferior wall, as shown by LV angiography immediately after PCI/Stent 6. Baseline LV ejection fraction <57% as assessed by Magnetic Resonance Imaging (MRI) 7. No previous infarction (late enhancement) in another territory as assessed by MRI 8. Written informed consent
Key exclusion criteria	1. Multi-vessel coronary artery disease requiring repeat PCI or coronary bypass 2. Pulmonary edema requiring intubation, cardiogenic shock 3. Pregnancy or unreliable contraception 4. Terminal illness or cancer 5. Advanced hepatic or renal disease, acute or chronic hepatitis, or Human Immunodeficiency Virus (HIV) infection 6. Acute systemic infection/inflammation or fever 7. Severe thrombocytopenia or anemia, coagulopathy 8. Known hypersensitivity or allergy to parts of the cell preparation reagents or other applied medicinal products (e.g. midazolam, etomidate) 9. Cardiac pacemaker or implantable cardioverter-defibrillator, claustrophobia and severe obesity 10. Patients participating in another investigational trial within the last 30 days 11. Any other condition which, in the judgement of the investigator, might increase the risk to the patient or preclude the satisfactory ability to collect trial relevant experimental or clinical data 12. Patients who were exposed to ionizing radiation within the last 10 years
Date of first enrolment	06/02/2006
Date of final enrolment	01/01/2015

Locations

Countries of recruitment

Bulgaria
Germany
Norway

Study participating centre

Hannover Medical School

Hannover
30625
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	14/10/2017	29/05/2020	Yes	No

Editorial Notes

29/05/2020: Publication reference and total final enrolment number added.
07/01/2014: Patient recruitment has been completed. The overall trial end date was changed from 13/12/2013 to 01/01/2015.
13/08/2010: The overall trial end date was changed from 31/12/09 to 13/12/2013.