Gao 2013.

Methods	Type of study: parallel RCT Type of publication: full Source of funding: grant of the National Advanced Technology Development Plan of China Country of origin: China Number of centres: 4 Dates of trial enrolment: 05/08 to 11/09 Length of follow‐up: 24 months Number (N) of participants randomised to each arm: 21 in the treatment arm, 22 in the control arm Number (N) of participants analysed (primary outcome) in each arm: 19 in the treatment arm, 20 in the control arm
Participants	Population: acute STEMI reperfused within 12 hours by PCI Age, mean (SD) each arm: 55 (SEM 1.6) years in treatment arm, 58.6 (SEM 2.5) years in control arm Sex, % male in each arm: 100% in treatment arm, 86.4% in control arm Number of diseased vessels: 1 (42.9%), 2 (19.0%), 3(38.1%) in treatment arm, 1 (50%), 2 (18.2%), 3 (31.8%) in control arm Number of stunned hyperkinetic, etc segments: not reported Time from symptom onset to initial treatment: 17.1 (SEM 0.6) days from reperfusion to infusion of cells Statistically significant baseline imbalances between the groups?: none
Interventions	Intervention arm: BM‐MSC Type of stem cells: bone marrow‐derived mesenchymal stromal cells (MSC) Summary of how stem cells were isolated and type and route of delivery: bone marrow (80 mL in 2000 IU of heparin) was harvested from each patient in the treatment group from the posterior iliac crest under local anaesthesia by a haematologist 2 to 3 days after primary PCI. The bone marrow aspirate was shipped at room temperature to the central cell‐processing laboratory. The mononuclear cell fraction was isolated using a density gradient with Lymphocyte Separation Medium (Biowhittaker) and then the low‐density cells were washed and viable cells were counted. The BM‐MCs were seeded into 75 cm² tissue culture flasks in MSCs medium consisting of Dulbecco's modified Eagle's medium containing 4.5% glucose (DMEM‐4.5, HyClone), supplemented with 10% fetal bovine serum (GIBCO) and 1% antibiotic‐antimycotic solution (Lift Technologies). The cell suspension was removed after 72 hours and the adherent cells were cultured in at 37 °C with 5% CO2. The culture medium was changed every 3 to 4 days until colonies were formed. After 14.6 ± 0.7 days of culture, passage 2 (P2) cells were harvested by trypsin treatment. Cells were washed, and viability was tested by trypan blue exclusion. Cell counts were performed, and the cells at 4 °C were delivered to the catheterisation laboratory. Cell were re‐suspended in heparinised saline Dose of stem cells: 3.08 (± 0.52) x 106 cells Timing of stem cell procedure: 16 to 17 days after PCI. Time from reperfusion to infusion of study therapy = 17.1 (SEM 0.6) days Comparator arm: no additional therapy (control)
Outcomes	Primary outcomes: absolute changes in myocardial viability and perfusion in the infarcted region measured by F‐18‐FDGi SPECT at 6 months, and in global LVEF measured by 2D echocardiogram at 6, 12 and 24 months after cell infusion Secondary outcomes: incidence of cardiovascular events, total mortality and adverse events at 12 and 24 months follow‐up Outcome assessment points:6, 12, 24 months Method(s): echocardiography, F‐18‐FDG SPECT
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised 1:1 to treatment or control using sequential numbers
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported
Blinding (performance bias and detection bias) All outcomes	High risk	The trial was described as "open label". Controls did not undergo bone marrow aspiration; no placebo was administered to controls. Echocardiography data were analysed independently by 2 experienced observers who were unaware of patients' treatment assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 participant (1/22) in the control arm was lost to follow‐up at 6 months and 1 patient (1/21) in the BMSC arm had died at 6 months follow‐up; all other randomised participants were included in the analysis of clinical and scientific outcomes at 6 months. 2 further participants (1 in each treatment group) were lost to follow‐up at 12 and 24 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