Meluzin 2008.

Methods	Type of study: parallel RCT Type of publication: full Source of funding: Ministry of Health, Czech Republic Country of origin: Czech Republic Number of centres: 1 Dates of trial enrolment: 11/03 to 08/05 Length of follow‐up: 12 months Number (N) of participants randomised to each arm: not reported (73 in total across both intervention arms and the control group) Number (N) of participants analysed (primary outcome) in each arm: 20 treatment/20 control. Extended study of high‐dose cell therapy versus controls: 37 in the treatment group and 36 in the control group
Participants	Population: AMI, within 24 hours Age, mean (SD) each arm: 54 (SEM 2) years in the high cell dose group, 54 (SEM 2) years in the low cell dose group, and 55 (SEM 2) years in control Sex, % male in each arm: 90% in the high cell dose group, 95% in the low dose group, and 90% in controls Number of diseased vessels: 1:14, 2:6, 3:0 (high dose); 1:11, 2:8, 3:1 (low dose); 1:14, 2:6, 3:0 in control Number of stunned hyperkinetic, etc segments: 0.4 (0.2) (high dose), 0.5 (0.2) (low dose), 0.4 (0.2) (controls). Irreversibly damaged segments: 6.2 (SEM 0.6) (high dose), 5.9 (SEM 0.5) (low dose), 6.1 (SEM 0.5) (controls) Time from symptom onset to initial treatment: 444 minutes (SEM 163 minutes) (high dose), 401 minutes (SEM 133 minutes) (low dose), 552 minutes (SEM 204 minutes) (controls) Statistically significant baseline imbalances between the groups?: none
Interventions	Intervention arm: BMMNC Type of stem cells: bone marrow‐derived stem cells (mononuclear cells‐MNC) Summary of how stem cells were isolated and type and route of delivery: BM aspirates after PCI. Cells were separated by density centrifugation. Cells cultivated overnight and re‐suspended in 22 mL prior to transplantation. Intracoronary infusion using an inflated balloon catheter. 7 balloon inflations for 3 minutes each, separated by 3‐minute intervals of balloon deflation. 3 mL BM cell suspension injected at each balloon deflation Dose of stem cells: 1 x 108 MNC (range 0.9 to 2 x 108 cells) (high dose) or 1 x 107 MNC (range 0.9 to 2 x 107 cells) (low dose) Timing of stem cell procedure: PCI within 24 hour of AMI symptoms, 3 to 7 days for randomisation, 5 to 9 days BM aspiration and infusion. Time from onset to cell transplantation: 6.8 (0.3) days (high dose) and 6.9 (0.3) days (low dose) Comparator arm: no additional therapy (control)
Outcomes	Primary outcomes: change in regional systolic function of the infarcted wall Secondary outcomes: changes in 1. LVEF, 2. LV volumes, 3. Perfusion defect size Outcome assessment points: baseline and 3, 6 and 12 months Method(s): SPECT and Echo
Notes	Data from the 2 active intervention arms of the trial are pooled in this review. 2 patients had fever and 1 patient had brachycardia, all within 20 hours prior to cells; these 3 patients were randomised to cell therapy (unclear whether high or low dose) but they did not receive cell therapy as randomised
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The trial was described as randomised but the method of randomisation was not reported
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported
Blinding (performance bias and detection bias) All outcomes	High risk	Blinding of participants and clinicians was not reported although controls did not undergo bone marrow aspiration and no placebo was administered. Echocardiographers were blinded to treatment assignment
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	From a total of 73 patients randomised to 1 of 3 treatment arms, 7 withdrew or were excluded from the analysis of all outcomes: 1 control patient was excluded because PET did not confirm the irreversibility of the myocardial damage and 2 controls underwent repeat MI 2 days after the hospital discharge due to in‐stent thrombosis. 3 patients randomised to BMSC were not transplanted because of complications within 20 hours before the procedure and a 4th patient was excluded because of an inadequate amount of implanted MBM cells; it was unclear whether these patients were randomised to high or low‐dose BMSC. 4 patients (cells: 2/22 versus no cells: 2/22) were missing from SPECT analysis at 3 and 12 months follow‐up; reasons for missing data were not reported. In separate publications, an expanded cohort of up to 73 patients (37 high dose cells and 36 controls) were included in SPECT analysis at 3, 6 and 12 months; the number of randomised patients was unclear
Selective reporting (reporting bias)	Unclear risk	All outcomes mentioned in the methods were reported in the results, although it would be difficult to rule out selective reporting
Other bias	Low risk	None reported or identified