Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study

Abstract

Objectives: We present here a sub-study of our prospective, randomized, double-blinded trial of bone marrow mononuclear cell (BMMC) transplantation with coronary artery bypass surgery (CABG) (ClinicalTrials.gov Identifier: NCT00418418), evaluating our secondary end-point concerning hospital stay as well as perioperative morbidity. Injecting a substantial amount of biologically active cells into a diseased myocardium inspires concerns for safety, a concern overlooked in previous trials.

Methods: We evaluated the immediate perioperative effects of intramyocardial injection of autologous BMMCs combined with CABG. In a randomized double-blinded manner, 39 patients received injections either of BMMCs (n = 20) or of vehicle medium (n = 19). The patients' haemodynamics, arterial blood gases, systemic vein oxygen level, blood glucose, acid-base balance, lactate, haemoglobin, body temperature and diuresis, as well as medications needed, were recorded in the operating theatre and in the intensive care unit (ICU) every 4 h throughout the first postoperative 24 h.

Results: No dissimilarities in these parameters were detectable. In the ICU, the median need for adrenaline was 0.0086 µg/kg/min (first quartile 0.0000, third quartile 0.0204) for controls and 0.0090 µg/kg/min (0.0000, 0.0353) for BMMC patients (P = 0.757); for noradrenaline, 0.0586 µg/kg/min (0.0180, 0.0888) for controls and 0.0279 µg/kg/min (0.0145, 0.0780) for BMMC patients (P = 0.405). The median stay at the ICU was 2 days for both groups (1, 2 for controls; 1, 3 for BMMCs; P = 0.967). Within the first postoperative day, one control patient had an elevated level of creatine kinase-myocardial band fraction mass (CK-MBm) up to >100 µg/l; no BMMC patient showed elevated CK-MBm levels (P = 0.474).

Conclusions: Both intramyocardial BMMC and placebo injections appear safe during surgery and immediate ICU stay after treatment of heart failure.

Keywords: Bone marrow cell; Clinical trial; Coronary artery bypass; Heart failure; Myocardial infarction; Patient safety.