thorn
30.01.2006, 16:46
Недавно в рассылке MedScape получил информацию по досрочно остановленному исследованию RESOLVE: Drotrecogin alfa неэффективен у детей при тяжелом сепсисе и увеличивает количество геморрагических осложнений в ЦНС.
SAN FRANCISCO (Reuters Health) Jan 12 - Results of the RESOLVE trial were announced here this week during a late-breaking clinical trials session at the 35th Critical Care Congress of the Society of Critical Care Medicine. The major finding was that drotrecogin alfa (Xigris; Eli Lilly) has no effect on reducing severe sepsis in children and increases the incidence of central nervous system (CNS) bleeding in infants. The trial has been halted early due to non-futility.
Drotrecogin significantly improved survival in adults with severe sepsis in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Trial. There was a 29% reduction in relative risk of death compared with placebo. The trial was halted early because of the strong positive result and the FDA granted approval of Xigris for this indication in November 2001.
In the FDA-mandated RESOLVE trial, researchers led by Dr. Brett Giroir of the Defense Advanced Research Projects Agency (DARPA) in Arlington, Virginia, tested the efficacy of drotrecogin in a pediatric population with severe sepsis.
The international trial involved 477 children randomized to either active drug or placebo. Co-investigator Dr. Brahm Goldstein of Oregon Health and Sciences University in Portland reported there was "a similar incidence of serious adverse events" in the two arms of the trial, occurring in 10.4% of children on drotrecogin and 11% on placebo during drug infusion. During 28 days of follow-up, the incidence was 18.3% in the study group and 19.0% in placebo patients.
Bleeding events were also similar in the two groups during infusion and follow-up, at 3.8% and 3.4% for drotrecogin and placebo, respectively, during infusion, and 6.7% and 6.8%, respectively, during follow-up.
"That was quite a surprise, actually," Dr. Mark Williams of Eli Lilly told Reuters Health. However, the incidence of CNS bleeding was higher with drotrecogin at 2.1% versus 0.4% with placebo. The higher incidence of CNS bleeding was confined to children less than two months of age. "The vasculature of the brain may be different in very young children," Dr. Williams speculated.
Similarly, Dr. Giroir reported, the efficacy of the drug was no higher than that of placebo in children with severe sepsis. The primary endpoint, Composite Time to Complete Organ Failure Resolution (CTCOFR) score, was 9.7 in the placebo group and 9.8 in the drotrecogin group. "There were no significant differences in resolution of individual organ dysfunction, Pediatric Overall Performance Category Scale and major amputations" in the two arms of the study, Dr. Giroir said.
Twenty-eight-day all-cause mortality was 17.45% in placebo patients and 17.15% in the study group.
Dr. Williams noted that the trial was not powered to completely evaluate efficacy. There is some indication that drotrecogin confers benefit in the subgroup of children with disseminated intravascular coagulopathy (DIC), but he pointed out that the FDA has not fully evaluated all of the data.
Xigris labeling has been changed from indicating that the safety and efficacy of the drug had not been evaluated in children to stating that Xigris is contraindicated for pediatric use.
Сначала было негативное ADDRESS ([Ссылки могут видеть только зарегистрированные и активированные пользователи]) у взрослых и вот опять неудача… :cool:
SAN FRANCISCO (Reuters Health) Jan 12 - Results of the RESOLVE trial were announced here this week during a late-breaking clinical trials session at the 35th Critical Care Congress of the Society of Critical Care Medicine. The major finding was that drotrecogin alfa (Xigris; Eli Lilly) has no effect on reducing severe sepsis in children and increases the incidence of central nervous system (CNS) bleeding in infants. The trial has been halted early due to non-futility.
Drotrecogin significantly improved survival in adults with severe sepsis in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Trial. There was a 29% reduction in relative risk of death compared with placebo. The trial was halted early because of the strong positive result and the FDA granted approval of Xigris for this indication in November 2001.
In the FDA-mandated RESOLVE trial, researchers led by Dr. Brett Giroir of the Defense Advanced Research Projects Agency (DARPA) in Arlington, Virginia, tested the efficacy of drotrecogin in a pediatric population with severe sepsis.
The international trial involved 477 children randomized to either active drug or placebo. Co-investigator Dr. Brahm Goldstein of Oregon Health and Sciences University in Portland reported there was "a similar incidence of serious adverse events" in the two arms of the trial, occurring in 10.4% of children on drotrecogin and 11% on placebo during drug infusion. During 28 days of follow-up, the incidence was 18.3% in the study group and 19.0% in placebo patients.
Bleeding events were also similar in the two groups during infusion and follow-up, at 3.8% and 3.4% for drotrecogin and placebo, respectively, during infusion, and 6.7% and 6.8%, respectively, during follow-up.
"That was quite a surprise, actually," Dr. Mark Williams of Eli Lilly told Reuters Health. However, the incidence of CNS bleeding was higher with drotrecogin at 2.1% versus 0.4% with placebo. The higher incidence of CNS bleeding was confined to children less than two months of age. "The vasculature of the brain may be different in very young children," Dr. Williams speculated.
Similarly, Dr. Giroir reported, the efficacy of the drug was no higher than that of placebo in children with severe sepsis. The primary endpoint, Composite Time to Complete Organ Failure Resolution (CTCOFR) score, was 9.7 in the placebo group and 9.8 in the drotrecogin group. "There were no significant differences in resolution of individual organ dysfunction, Pediatric Overall Performance Category Scale and major amputations" in the two arms of the study, Dr. Giroir said.
Twenty-eight-day all-cause mortality was 17.45% in placebo patients and 17.15% in the study group.
Dr. Williams noted that the trial was not powered to completely evaluate efficacy. There is some indication that drotrecogin confers benefit in the subgroup of children with disseminated intravascular coagulopathy (DIC), but he pointed out that the FDA has not fully evaluated all of the data.
Xigris labeling has been changed from indicating that the safety and efficacy of the drug had not been evaluated in children to stating that Xigris is contraindicated for pediatric use.
Сначала было негативное ADDRESS ([Ссылки могут видеть только зарегистрированные и активированные пользователи]) у взрослых и вот опять неудача… :cool: