title: Cellular therapy with Ixmyelocel-T to treat critical limb ischemia: the randomized, double-blind, placebo-controlled RESTORE-CLI trial.
abstract: Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adverse events. Efficacy assessments included time to first occurrence of treatment failure (TTF; major amputation of injected leg; all-cause mortality; doubling of total wound surface area from baseline; de novo gangrene) and amputation-free survival (AFS; major amputation of injected leg; all-cause mortality). A total of 77 patients underwent bone marrow or sham aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24 patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically meaningful 32% reduction in event rate that was not statistically significant (P = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank test). Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. Richard.Powell@hitchcock.org
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Powell
authors.forename: William A
authors.initials: WA
authors.lastname: Marston
authors.forename: Scott A
authors.initials: SA
authors.lastname: Berceli
authors.forename: Raul
authors.initials: R
authors.lastname: Guzman
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: Amy T
authors.initials: AT
authors.lastname: Longcore
authors.forename: Theresa P
authors.initials: TP
authors.lastname: Stern
authors.forename: Sharon
authors.initials: S
authors.lastname: Watling
authors.forename: Ronnda L
authors.initials: RL
authors.lastname: Bartel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D017690:Cell Transplantation / Q000009:adverse effects; D005260:Female; D006801:Humans; D007511:Ischemia / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D035002:Lower Extremity / Q000098:blood supply*; D008264:Macrophages / Q000637:transplantation*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome