Wollert 2004.

Methods	Type of study: parallel RCT Type of publication: full Source of funding: Department of Cardiology, Hannover Medical School, Hannover Country of origin: Germany Number of centres: 1 Dates of trial enrolment: 01/02 to 05/03 Length of follow‐up: 60 months Number (N) of participants randomised to each arm: 33 in treatment arm/32 in control arm Number (N) of participants analysed (primary outcome) in each arm: 30 in treatment arm/30 in control arm
Participants	Population: AMI, within 5 days Age, mean (SD) each arm: 53.4 (14.8) years in treatment arm, 59.2 (13.5) years in control arm Sex, % male in each arm: 67% in treatment arm, 73% in control arm Number of diseased vessels: 1 in both arms (23% right artery/77% left artery) Number of stunned hyperkinetic, etc segments: >2/3 LV anteroseptal, lateral or inferior wall in both arms Time from symptom onset to initial treatment: median 9.8 days (range 2 to 22 days) in treatment arm/median 8.0 days (range 3 to 12 days) in control arm 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 aspirate (128 +/‐ 33 mL) post baseline cardiac MRI Separation of MNC using a 4% gelatin‐polysuccinate density gradient, under GMP regulations. Cells re‐suspended in saline with 10,000 U/L of heparin. Between 6 and 8 hours after isolation, cells were infused. Intracoronary infusion using a balloon catheter carried out as 4 to 5 coronary occlusions each lasting 2.6 to 4 minutes Dose of stem cells: a single dose of 2.46 +/‐ 0.94 x 109 MNC, of which 9.5 +/‐ 6.3 x 106 CD34+ and 3.6 +/‐ 3.4 x 06 form colonies in CFU assays Timing of stem cell procedure: PCI within 5 days of MI onset. 4.8 +/‐ 1.3 days after PCI the BMSC were infused G‐CSF details: no G‐CSF Comparator arm: no additional therapy (control)
Outcomes	Primary outcomes: changes in global LVEF Secondary outcomes: changes in: 1. LVEF (%), 2. LVEDV (mL), 3. LVESV (mL), 4. LV mass index (g/m²), 5. Wall thickening: infarct region (%), 6. wall thickening: border zone (%), 7. wall motion: infract region (mm), 8. wall motion: border zone (mm), 9. late contract enhancement volume (LE, mL) Outcome assessment points: baseline, 6, 18, 60 months Method(s): MRI
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Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised to treatment or control in a 1:1 ratio using sequentially numbered, sealed envelopes provided by an institute external to the trials
Allocation concealment (selection bias)	Low risk	Sequentially numbered, sealed envelopes were provided by another institute
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. Echocardiography and MRI analyses were performed by 2 investigators blinded to treatment assignments
Incomplete outcome data (attrition bias) All outcomes	Low risk	5 patients (BMSC: 3/33 versus control: 2/32) were withdrawn at the start of the study as "not been able to undergo MRI because of severe obesity or claustrophobia". All other patients were included in analysis of clinical and scientific outcomes
Selective reporting (reporting bias)	Low risk	All outcomes described in the trial protocol (www.clinicaltrials.gov: NCT00224536) were reported
Other bias	Low risk	None reported or identified