Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial  

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Nadel, Simon ; Goldstein, Brahm ; Williams, Mark D. ; Dalton, Heidi ; Peters, Mark J. ; Macias, William L. ; Abd-Allah, Shamel A. ; Levy, Howard B. ; Angle, Robinette ; Wang, Dazhe ; Sundin, David P.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The Lancet (keterangan: ada di Proquest) vol. 369 no. 9564 (Mar. 2007), page 836.

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Perpustakaan FK Nomor Panggil: L01.K.2007.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Background Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. Methods Children aged between 38 weeks' corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 J1g/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov, number NCTOO049764. : Findings 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Our results showed no significant ; difference between groups in CTCOFR score (p=0.72) orin 28-daymortality (placebo 17.5%; DrotAA, 17 .2%; p=0.93). , Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6.8%; ; DrotAA 6.7%; p=0.97), there were numerically more instances ofCNS bleeding in the DrotAA group (11 [4.6%], ~ vs 5 [2.1%] in placebo, p=O.13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation c coefficient was -0.016 (95% CI -0.106 to 0.74); relative risk for 28-day mortality was 1.06 (95% CI 0.66 to 1.46) for " DrotAA compared with placebo. Interpretation Although we did not record any efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days. IS However, we gained important insights into clinical and laboratory characteristics of childhood severe sepsis, and have identified issues that need to be addressed in future trials in critically ill children.

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