RT info:eu-repo/semantics/article T1 Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limbischaemia A1 Belch, Jill J.F. A1 Hiat, William R. A1 Baumgartner, Iris A1 Vickie Driver, I. A1 Nikol, Sigrid A1 Largen, Lars A1 Vaquero Puerta, Carlos K1 Isquemia articular-tratamiento AB Background Patients with critical limb ischaemia have a high rate of amputation and mortality. We tested thehypothesis that non-viral 1 fi broblast growth factor (NV1FGF) would improve amputation-free survival.Methods In this phase 3 trial (EFC6145/TAMARIS), 525 patients with critical limb ischaemia unsuitable forrevascularisation were enrolled from 171 sites in 30 countries. All had ischaemic ulcer in legs or minor skin gangreneand met haemodynamic criteria (ankle pressure <70 mm Hg or a toe pressure <50 mm Hg, or both, or atranscutaneous oxygen pressure <30 mm Hg on the treated leg). Patients were randomly assigned to either NV1FGFat 0·2 mg/mL or matching placebo (visually identical) in a 1:1 ratio. Randomisation was done with a central interactivevoice response system by block size 4 and was stratifi ed by diabetes status and country. Investigators, patients, andstudy teams were masked to treatment. Patients received eight intramuscular injections of their assigned treatmentin the index leg on days 1, 15, 29, and 43. The primary endpoint was time to major amputation or death at 1 yearanalysed by intention to treat with a log-rank test using a multivariate Cox proportional hazard model. This trial isregistered with ClinicalTrials.gov, number NCT00566657.Findings 259 patients were assigned to NV1FGF and 266 to placebo. All 525 patients were analysed. The mean agewas 70 years (range 50–92), 365 (70%) were men, 280 (53%) had diabetes, and 248 (47%) had a history of coronaryartery disease. The primary endpoint or components of the primary did not diff er between treatment groups, withmajor amputation or death in 86 patients (33%) in the placebo group, and 96 (36%) in the active group (hazardratio 1·11, 95% CI 0·83–1·49; p=0·48). No signifi cant safety issues were recorded.Interpretation TAMARIS provided no evidence that NV1FGF is eff ective in reduction of amputation or death in patientswith critical limb ischaemia. Thus, this group of patients remains a major therapeutic challenge for the clinician. PB Lancet Publishing Group YR 2011 FD 2011 LK http://uvadoc.uva.es/handle/10324/2868 UL http://uvadoc.uva.es/handle/10324/2868 LA eng NO Lancet, June, vol.377, june 4 p.1929-37 DS UVaDOC RD 29-mar-2024