title: All-cause mortality imbalance in the tigecycline phase 3 and 4 clinical trials.
abstract: In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality.
authors.affiliation: Pfizer Inc, Collegeville, PA 19426, USA. paul.mcgovern@pfizer.com
authors.forename: Paul C
authors.initials: PC
authors.lastname: McGovern
authors.forename: Michele
authors.initials: M
authors.lastname: Wible
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Tahtawy
authors.forename: Pinaki
authors.initials: P
authors.lastname: Biswas
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Meyer
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D000078304:Tigecycline; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline