Major Non-cardiac Surgery Clinical Trial
Official title:
Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery : a Randomized, Multicentre, Double Blind, Study
Postoperative complications are major healthcare problems and are associated with a reduced
short-term and long-term survival after surgery. Major surgery is associated with a
predictable and usually transient Systemic Inflammatory Response (SIRS), depending on the
magnitude of the surgical trauma. An excessive SIRS syndrome participates to the development
of postoperative organ dysfunction, infection and mortality. Corticosteroids may decrease the
postsurgical SIRS in cardiac surgery: in a large multicenter randomized trial, a single
intravenous administration of high-dose dexamethasone did not reduce the incidence of a
composite endpoint of adverse events but was associated with a reduced incidence of
postoperative pulmonary complications and infections and with a reduction in hospital stay.
However, a similar study, recently published in the Lancet was negative. Evidences from one
meta-analysis, including 11 studies of moderate quality (439 patients in total), suggest that
intraoperative administration of corticosteroids during major abdominal surgery decreases
postoperative complications, including infectious complications, without significant risk of
anastomotic leakage. At present, no large randomized controlled trial has been performed in
patients undergoing major non-cardiac surgery. In acute medicine, several lines of evidence
have shown that low to moderate doses of corticosteroids decrease the excessive inflammatory
response, without inducing immuno suppression. However, despite the widespread use of
corticosteroids to reduce postoperative nausea and vomiting and to improve analgesia,
concerns continue to be raised about their safety, especially regarding an increased risk of
postoperative infection.
We hypothesize that the perioperative administration of glucocorticoids would reduce
postoperative morbidity after major non-cardiac surgery through dampening of the inflammatory
response. Given the number of surgical patients for whom the question applies, the study is
of significant clinical importance
Background :
Postoperative complications are major healthcare problems and are associated with a reduced
short-term and long-term survival after surgery. Corticosteroids may decrease the
postsurgical SIRS in cardiac surgery, but this treatment is not recommended yet. The aim of
the current study is to assess the efficiency and the safety of dexamethasone to prevent on
postoperative complications.
Methods :
The PACMAN trial is a multicenter, randomized, controlled, double-blind, two-arms study. 1222
patients undergoing major surgery (duration >90 minutes and one or more risk factor of
postoperative complication) are randomized to dexamethasone (0.2mg/kg at the end of the
surgery and at day1) or to placebo. The primary outcome is a composite outcome of major
postoperative complication during 14 days after the surgery.
Analyzes will be conducted, first, on data from the intention-to-treat (ITT) population,
second, in the modified intention-to-treat (mITT) population as well as in the per-protocol
population. All statistical analyzes will take into account stratified randomization (cancer
and type of surgery) and will be adjusted on the center as random effect as.
Discussion :
The PACMAN trial is the first randomized controlled trial powered to investigate whether
perioperative administration of dexamethasone in high risk patients improve outcomes.
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