Schachinger 2006.

Methods	Type of study: parallel RCT Type of publication: full Source of funding: research grant from Guidant and support from Eli Lilly Country of origin: Germany and Switzerland Number of centres: 17 (16 in Germany + 1 in Switzerland) Dates of trial enrolment: 04/04 to 04/05 Length of follow‐up: 5 years Number (N) of participants randomised to each arm: 101 in the treatment arm/103 in control arm Number (N) of participants analysed (primary outcome) in each arm: 95 in treatment arm/92 in control arm
Participants	Population: AMI, within 5 days Age, mean (SD) each arm: 55 (11) years in treatment arm, 57 (11) years in control arm Sex, % male in each arm: 82% in treatment arm, 82% in control arm Number of diseased vessels: 1:61; 2:24; 3:16 in treatment arm/1:60; 2:32; 3:11 in control arm Number of stunned hyperkinetic, etc segments: not reported Time from symptom onset to initial treatment: 7.5 (8.0) hours to PCI in treatment arm/7.0(6.5) hours to PCI 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 aspirates 3 to 6 days after PCI, cells were separated by Ficoll gradient centrifugation and re‐suspended in 10 mL of X‐VIVO medium containing 20% autologous serum. Intracoronary infusion using an inflated balloon catheter. 3 portions of 3.3 mL cell suspension were infused in 3‐minute occlusion time for each portion and 3‐minute intervals Dose of stem cells: 10 mL of a single dose containing 2.36 (1.74) x 108 mononuclear cells Timing of stem cell procedure: PCI within 12 hrs of AMI symptoms, harvest 3 to 6 days after PCI, randomisation and transport prior to infusion 3 to 6 days Comparator arm: placebo consisting of 10 mL X‐VIVO medium with 20% autologous serum
Outcomes	Primary outcomes: changes in LVEF Secondary outcomes: 1. Improvement of global LVEF, 2. Reduction of LVESV, 3. Improvement of regional wall motion and myocardial contractility, 4. Assessment of major adverse events, such as revascularisation, death and hospitalisation due to heart failure Outcome assessment points: baseline, 4, 12, 24 months, 5 years Method(s): LV angiography
Notes	3 patients randomised to the placebo arm did not receive placebo medium but were included in the analysis: 1 patient in placebo group had angiographic evidence of a thrombus in a non‐infarct‐related artery, 1 patient had an air embolism during initial angiography before the guidewire could be advanced and in 1 patient the guidewire could not be advanced into the infarct‐related artery
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was carried out using computer‐generated randomised lists maintained at a site external to the trial
Allocation concealment (selection bias)	Low risk	Bone marrow aspirates were sent to the cell processing centre (centralisation)
Blinding (performance bias and detection bias) All outcomes	Low risk	All patients underwent bone marrow aspiration and control group patients were given an intracoronary injection of placebo medium. Bone marrow aspirates were then sent to a central cell processing centre; participants and clinicians were therefore blinded to treatment. LV angiography was performed by an experienced investigator in a central core laboratory who was unaware of the patient's treatment assignment until after analysis of 4‐month data was complete. Study centres and investigators and those entering the data into databases remained blinded until 12‐month follow‐up was complete.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised patients were included in the analysis of clinical outcomes at 4 months follow‐up; 3 and 2 patients in the control group were lost to follow‐up at 12 months and 2 years respectively. In the analysis of scientific outcomes, 6/101 in the BMSC group and 11/103 in the placebo group were missing from LV angiography analysis at 4 months (2 had poor quality results on angiography, 4 deaths before 4 months, 5 declined and 6 did not undergo angiography). A subset of 59 patients were included in a sub‐study of MRI 2 years
Selective reporting (reporting bias)	Low risk	All outcomes described in the trial protocol (www.clinicaltrials.gov: NCT00279175) were reported, with the exception of NYHA class, although all other pre‐specified morbidity outcomes were reported
Other bias	High risk	This is a commercially funded trial