Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery
- Registration Number
- NCT03218553
- Lead Sponsor
- Nantes University Hospital
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1222
Major surgery (> 90 minutes and realized under general anesthesia) of the abdomen, pelvis, thorax, face/neck, vascular surgery in a patient older than 65 years Or Major surgery (> 90 minutes and realized under general anesthesia) of the abdomen, pelvis, thorax, face/neck, vascular surgery in a patient older than 50 years and presenting one of the following criteria
- Presence of a defined risk factor for cardiac or respiratory disease (exercise tolerance equivalent to 6 metabolic equivalents or less)
- Medical history of stroke
- Moderate to severe renal impairment (clearance of creatinine ≤ 30 mll/L)
- Active smoking
- Averaged observed blood losses over 500 ml
- Emergency surgery
- Pregnant women, Minors, Adults under guardianship or trusteeship
- Treatment with systemic corticosteroids at a dose > 5 mg.day-1 of equivalent prednisolone in the previous 3 months
- Patients with chronic renal failure (clearance of creatinine < 10 ml/min)
- Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 1 month
- Patient with preoperative shock (defined by the need for vasoactive drugs before surgery)
- Acute Pulmonary edema in the last 7 days
- Active bacterial or viral infection
- Allergy to the intravenous formulation of dexamethasone
- Uncontrolled psychotic disorder (acute or chronical)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo Placebos Standard cares plus postoperative administrations of placebo Dexamethasone Dexamethasone Standard cares plus postoperative administrations of glucocorticoid
- Primary Outcome Measures
Name Time Method Composite outcome at least one item among the following:-Postoperative sepsis, severe sepsis, septic shock-Postoperative pulmonary complication: pneumonia, need for invasive and/or noninvasive ventilation for respiratory failure-All-cause mortality 14 days
- Secondary Outcome Measures
Name Time Method Rate of patients developing postoperative organ failures 28 days Rate of patients with postoperative respiratory failure requiring non-invasive ventilation 28 days All cause mortality 28 days Postoperative intubation rate for respiratory failure 28 days Postoperative respiratory failure requiring invasive ventilation
Hospital free days 28 days Rate of patients with post operative sepsis 28 days Blood level of marker of inflammation (C Reactive protein) 28 days Delayed healing defined as non hermetic scar 28 days ICU length of stay 28 days Rate of patients with Gastric ulcer 28 days Rate of patients with Digestive bleeding 28 days Rate of patients with Anastomotic leakage 28 days Dose of insulin 3 days Surgical complications 28 days The Clavien-Dindo classification
Duration of hospitalization 28 days Rate of unplanned hospitalization in intensive care unit 28 days Rate of patients with Hypokaliemia (< 4 mmol/l) 28 days Rate of patients with Dysnatremia (<139 mmol/l or > 145 mmol/l) 28 days Rate of patients with Hypocalcemia (<2.2 mmol/l) 28 days Rate of patients with Cardiac events (Atrial fibrillation / cardiac flutter, Acute coronary syndrome or Cardiac failure) 28 days
Trial Locations
- Locations (29)
Hôpital Beaujon
🇫🇷Clichy, France
CHU La Cavale Blanche
🇫🇷Brest, France
Hôpital Claude Huriez
🇫🇷Lille, France
CHU de Poitiers
🇫🇷Poitiers, France
Ch Quimper
🇫🇷Quimper, France
CHU Saint Etienne
🇫🇷Saint-Étienne, France
CHU de Toulouse
🇫🇷Toulouse, France
CH Valenciennes
🇫🇷Valenciennes, France
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU Angers
🇫🇷Angers, France
Hôpital Estaing, CHU de Clermont Ferrand
🇫🇷Clermont Ferrand, France
Centre Hospitalier Du Mans
🇫🇷Le Mans, France
CHD Vendée
🇫🇷La Roche-sur-Yon, France
Hopital Edouard Herriot
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Hôpital Timone
🇫🇷Marseille, France
Clinique Jules Verne
🇫🇷Nantes, France
Hôpital Nord
🇫🇷Marseille, France
Hôpital Saint-Eloi
🇫🇷Montpellier, France
Le Confluent
🇫🇷Nantes, France
C.R.L.C.C. Nantes Atlantique
🇫🇷Nantes, France
Hotel Dieu Nantes
🇫🇷Nantes, France
Hôpital Laennec
🇫🇷Nantes, France
Hôpital Saint Antoine
🇫🇷Paris, France
CHU Lyon Sud
🇫🇷Pierre-Bénite, France
Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand Widal
🇫🇷Paris, France
Hôpital Pontchaillou
🇫🇷Rennes, France
CHU de Rouen
🇫🇷Rouen, France
Nouvel Hôpital Civil
🇫🇷Strasbourg, France