Yao 2009.

Methods	Type of study: parallel RCT Type of publication: full Source of funding: Shanghai Scientific Research Fund (06DJ14001), Program for Shanghai Outstanding Medical Academic Leader (LJ06008), National Basic Research Program of China (2006CB943704), and Science Foundation for Youth of Shanghai Medical Administrative Bureau (2008Y044) Country of origin: Italy Number of centres: 1 Dates of trial enrolment: 03/04 to 02/06 Length of follow‐up: 12 months Number (N) of participants randomised to each arm: 15 in single cell transfer arm (ST), 15 in repeated cell transfer arm (RT) and 15 in control arm Number (N) of participants analysed (primary outcome) in each arm: 12 (ST), 15 (RT), 12 (controls)
Participants	Population: AMI, within 12 hours. Age, mean (SD) each arm: 52.1 (6.3) years in ST arm, 51.3 (7.4) years in RT arm, 52.7 (7.8) years in control arm Sex, % male in each arm: 83.3% in ST arm, 80.0% in RT arm, 91.7% control arm Number of diseased vessels: ST arm: 1 vessel disease = 4/12 (33.33%), 2 vessel disease 5/12 (41.67%), 3 vessel disease 3/12 (25.00%) RT arm: 1 vessel disease = 5/15 (33.33%), 2 vessel disease 6/15 (40.00%), 3 vessel disease 4/15 (26.67%) Controls: 1 vessel disease = 3/12 (25.00%), 2 vessel disease 6/12 (50.00%), 3 vessel disease 3/12 (25.00%) Number of stunned hyperkinetic, etc segments: not reported Time from symptom onset to initial treatment: from AMI to PCI: 4.9 (2.9) hours (ST), 4.7(2.9) hours (RT), 6.0 (2.8) hours (controls) Statistically significant baseline imbalances between the groups?: none
Interventions	Intervention arm: single BMMNC dose (SD) or repeated BMMNC dose (DD) 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: 90 ± 18 mL bone marrow was aspirated from the posterior superior iliac spine under local anaesthesia. Bone marrow aspirates were diluted with 0.9% NaCl (1:5) and mononuclear cells were isolated by density gradient centrifugation, washed 3 times with PBS and then suspended in 16 mL heparin‐treated plasma at a density of (1.3 ± 1.0) x 107 cells/mL at room temperature. Cell transplantation via intracoronary route using an over‐the‐wire balloon catheter inserted into the stent that was implanted during primary PCI. Procedure repeated at 3 months in repeated cell dose arm Dose of stem cells: mean 1.9 (SE 1.2) x 108 BMC (ST), 2.0 (SE 1.4) x 108 (RT, first delivery), 2.1 (SE 1.7) x 108 (RT, second delivery at 3 months) Timing of stem cell procedure: BMC infusion 3 to 7 days after PCI, and 3 hours after BMC collection, followed by saline infusion (ST group) or second infusion (RT group) 3 months after PCI Comparator arm: saline infusion 3 to 7 days after PCI (no secondary infusion at 3 months)
Outcomes	Primary outcomes: LVEF, LVEDV, LVESV Secondary outcomes: myocardial infarct area, myocardial perfusion defect, survival, re‐hospitalisation for congestive heart failure, serious adverse events Outcome assessment points: baseline, 6 and 12 months Method(s): MRI, SPECT, LV angiography
Notes	Data from the 2 active intervention arms of the trial are pooled in this review. 3 patients randomised to single dose BMSC were not transplanted as follows: 1 patient could not undergo MRI due to pacemaker implantation following development of bradycardia, 1 patient developed a fever 12 hours prior to the procedure, and in 1 patient an inadequate amount of cells was acquired
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was undertaken using a computer‐generated random number sequence
Allocation concealment (selection bias)	Low risk	Sequentially numbered, sealed, opaque envelopes were used
Blinding (performance bias and detection bias) All outcomes	High risk	Although the control group received a placebo, only the active treatment groups (single or double dose) underwent BM aspiration. Further, the active treatment groups were recalled for the second infusion of cells or placebo whereas the control group was not recalled for further treatment. Participants were therefore not appropriately blinded. Blinding of clinicians was not reported. MRI and SPECT studies were processed and evaluated at the MRI and scintigraphy core laboratories respectively by experienced operators who were blinded to the assigned therapy
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients in the repeat BMSC arm were included in the analysis of all outcomes. 3 patients in the single BMSC arm and 3 patients in the control arm (3/15) were withdrawn or excluded from the analysis of all outcomes. In the BMSC arm, 1 patient developed a fever 12 hours prior to the procedure, for one patient an inadequate amount of cells was acquired and one patient could not undergo MRI due to pacemaker implantation following development of bradycardia. In the control arm, 1 patient had a reinfarction 5 days after discharge due to in‐stent thrombosis, 1 patient was excluded due to diagnosis of liver cancer at 4 months, and 1 patient could not be contacted at 3 months follow‐up. One additional patient in the control group was missing from MRI analysis at 12 months follow‐up.
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