Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery
Condition: Major Non-cardiac Surgery
MeSH terms: Postoperative Complications
Study type: Interventional
Phase: Phase 3

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): Dexamethasone; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): Dexamethasone : first dose : 0,2mg.kg-1 at the end of the surgical procedure, second dose (0,2 mg.kg-1) 24 hours after the surgery; placebo : first infusion at the end of the surgical procedure, second 24 hours after the surgery
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment