NCT03218553: PACMAN

Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery

Completed Phase 3 Last updated 1 June 2020

What this trial tests

Phase 3 trial testing Dexamethasone in Major Non-cardiac Surgery in 1,222 participants. Completed in 16 April 2019.

Timeline

13 December 2017

Primary endpoint
16 April 2019

16 April 2019

Quick facts

Lead sponsor	Nantes University Hospital
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	1,222
Start date	13 December 2017
Primary completion	16 April 2019
Estimated completion	16 April 2019
Sites	29 locations across France

Drugs / interventions tested

• Dexamethasone (dexamethasone) — full drug profile →
• Placebos — full drug profile →

Conditions studied

• Major Non-cardiac Surgery — all drugs for Major Non-cardiac Surgery →

Sponsor

Nantes University Hospital

Who can join

Adults 50 to 90, any sex, with Major Non-cardiac Surgery. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.
   Weibel S, Rücker G, Eberhart LH, Pace NL, et al · · 2020 · cited 125× · PMID 33075160 · DOI 10.1002/14651858.cd012859.pub2
2. Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial.
   Asehnoune K, Le Moal C, Lebuffe G, Le Penndu M, et al · · 2021 · cited 26× · PMID 34078591 · DOI 10.1136/bmj.n1162
3. ESICM LIVES 2020.
   · 2020 · cited 13× · PMID 33313986 · DOI 10.1186/s40635-020-00354-8
4. PACMAN trial protocol, Perioperative Administration of Corticotherapy on Morbidity and mortality After Non-cardiac major surgery: a randomised, multicentre, double-blind, superiority study.
   Asehnoune K, Futier E, Feuillet F, Roquilly A, et al · · 2019 · cited 6× · PMID 30904834 · DOI 10.1136/bmjopen-2017-021262