Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: The G-CSF in Angina patients with IHD to stimulate Neovascularization (GAIN I) trial
Received 18 September 2007; accepted 14 April 2008.
Background
Preclinical studies suggest granulocyte-colony stimulating factor (G-CSF) holds promise for treating ischemic heart disease; however; its clinical safety and efficacy in this setting remain unclear. We elected to evaluate the safety and efficacy of G-CSF administration in patients with refractory “no-option” ischemic heart disease.
Methods
Twenty patients (18 males, 2 females, mean age 62.4 years) were enrolled and underwent baseline cardiac ischemia assessment (CA) (angina questionnaire, exercise stress test [EST], technetium Tc 99m sestamibi and dobutamine-stress echocardiographic imaging). Patients then received open-label G-CSF commencing at 10 μg/kg SC for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF + ESTs were repeated but, in addition, leukapheresis and a randomized double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final CA occurred 3 months thereafter.
Results
There were no deaths, but only 16 patients were permitted to complete the study. Eight events fulfilled prespecified “adverse event” criteria, including 4 troponin I–positive events and 2 episodes of thrombocytopenia. Also, frequent minor troponin I–positive events (troponin I <0.9 μg/L) were observed, which did not meet adverse event criteria. The administration of consecutive cycles of G-CSF resulted in stepwise improvements in anginal frequency, EST performance, and Duke treadmill scores (all P < .005). However, from baseline to final follow-up, technetium Tc 99m sestamibi and dobutamine-stress echocardiographic results were unchanged.
Conclusions
Granulocyte-colony stimulating factor administration was associated with improvement in a range of subjective outcomes. However, adverse events were common, and objective measures of cardiac perfusion/ischemia were unchanged.
aVictor Chang Cardiac Research Institute, University of New South Wales, Sydney, New South Wales, Australia
bSt Vincent's Hospital, University of New South Wales, Sydney, New South Wales, Australia
cFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
eCurrent appointment: Translational Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD
Reprint requests: Robert Graham, FRACP, MD, Victor Chang Cardiac Research Institute, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
The study was approved by the St Vincent's Hospital human research ethics committee, registered with the Australian Clinical Trials Registry (no. 12605000050651), supervised by an independent data and safety monitoring board (DSMB), and conducted with the informed consent of all subjects. Enrollment commenced January 2004, with the final follow-up scan performed July 2006.
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