title: Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia.
abstract: BACKGROUND
  Patients with critical limb ischaemia (CLI) unsuitable for revascularisation have a high rate of amputation and mortality (30% and 25% at 1 year, respectively). Localised gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pecaplasmid) has showed an increased amputation-free survival in a phase II trial. This article provides the rationale, design and baseline characteristics of CLI patients enrolled in the pivotal phase III trial (EFC6145/TAMARIS).
  
  
  METHODS
  An international, double-blind, placebo-controlled, randomised study composed of 525 CLI patients recruited from 170 sites worldwide who were unsuitable for revascularisation and had non-healing skin lesions was carried out to evaluate the potential benefit of repeated intramuscular administration of NV1FGF. Randomisation was stratified by country and by diabetic status.
  
  
  RESULTS
  The mean age of the study cohort was 70 ± 10 years, and included 70% males and 53% diabetic patients. Fifty-four percent of the patients had previous lower-extremity revascularisation and 22% had previous minor amputation of the index leg. In 94% of the patients, the index leg had distal occlusive disease affecting arteries below the knee. Statins were prescribed for 54% of the patients, and anti-platelet drugs for 80%. Variation in region of origin resulted in only minor demographic imbalance. Similarly, while diabetic status was associated with a frequent history of coronary artery disease, it had little impact on limb haemodynamics and vascular lesions.
  
  
  CONCLUSIONS
  Clinical characteristics and vascular anatomy of CLI patients with ischaemic skin lesions who were unsuitable for revascularisation therapy show little variations by region of origin and diabetic status. The findings from this large CLI cohort will contribute to our understanding of this disease process. This study is registered with ClinicalTrials.gov, number NCT00566657.
authors.affiliation: Department of Cardiology, CHRU de Lille and EA 2693, University Lille-Nord de France, 59037 Lille Cedex, France. ericvanbelle@aol.com
authors.forename: E
authors.initials: E
authors.lastname: Van Belle
authors.forename: S
authors.initials: S
authors.lastname: Nikol
authors.forename: L
authors.initials: L
authors.lastname: Norgren
authors.forename: I
authors.initials: I
authors.lastname: Baumgartner
authors.forename: V
authors.initials: V
authors.lastname: Driver
authors.forename: W R
authors.initials: WR
authors.lastname: Hiatt
authors.forename: J
authors.initials: J
authors.lastname: Belch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000150:complications / Q000188:drug therapy*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000627:therapeutic use*; D006801:Humans; D038622:Internationality; D007511:Ischemia / Q000209:etiology*; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D012107:Research Design
chemical_list: D043925:Angiogenesis Inducing Agents; C554637:riferminogene pecaplasmide; D016220:Fibroblast Growth Factor 1