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

NCT03218553 | Completed Phase 3 DMC

• 1 other identifier: RC17_0029
• Study Type: interventional
• Target: 1,222
• Locations: 1 country
• Sites: 29

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

Conditions

Major Non-cardiac Surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• All cause mortality

  28 days

• Hospital free days

  28 days

• Rate of patients with post operative sepsis

  28 days

• Postoperative intubation rate for respiratory failure

  28 days

• Rate of patients with postoperative respiratory failure requiring non-invasive ventilation

  28 days

Study Arms (2)

Dexamethasone

EXPERIMENTAL

Standard cares plus postoperative administrations of glucocorticoid

Drug: Dexamethasone

placebo

PLACEBO COMPARATOR

Standard cares plus postoperative administrations of placebo

Drug: Placebos

Interventions

Dexamethasone DRUG

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

Dexamethasone

Placebos DRUG

placebo : first infusion at the end of the surgical procedure, second 24 hours after the surgery

placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (29)

CHU Angers

Angers, 49933, France

Location

CHU La Cavale Blanche

Brest, 29609, France

Location

Hôpital Estaing, CHU de Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hôpital Beaujon

Clichy, 92110, France

Location

CHD Vendée

La Roche-sur-Yon, 85000, France

Location

Centre Hospitalier Du Mans

Le Mans, 72037, France

Location

Hôpital Claude Huriez

Lille, 59037, France

Location

Hopital Edouard Herriot

Lyon, 69003, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Hôpital Timone

Marseille, 13385, France

Location

Hôpital Nord

Marseille, 13975, France

Location

Hôpital Saint-Eloi

Montpellier, 34295, France

Location

Clinique Jules Verne

Nantes, 44000, France

Location

Le Confluent

Nantes, 44000, France

Location

Hotel Dieu Nantes

Nantes, 44093, France

Location

Hôpital Laennec

Nantes, 44093, France

Location

C.R.L.C.C. Nantes Atlantique

Nantes, 44805, France

Location

Hôpital Saint Antoine

Paris, 75000, France

Location

Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand Widal

Paris, 75475, France

Location

CHU Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

Ch Quimper

Quimper, 29107, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

CHU de Rouen

Rouen, 76031, France

Location

CHU Saint Etienne

Saint-Etienne, 42055, France

Location

Nouvel Hôpital Civil

Strasbourg, 67098, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

CH Valenciennes

Valenciennes, 59300, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (2)

• Asehnoune K, Le Moal C, Lebuffe G, Le Penndu M, Josse NC, Boisson M, Lescot T, Faucher M, Jaber S, Godet T, Leone M, Motamed C, David JS, Cinotti R, El Amine Y, Liutkus D, Garot M, Marc A, Le Corre A, Thomasseau A, Jobert A, Flet L, Feuillet F, Pere M, Futier E, Roquilly A; PACMAN study group. Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial. BMJ. 2021 Jun 2;373:n1162. doi: 10.1136/bmj.n1162.

  PMID: 34078591 DERIVED

• Asehnoune K, Futier E, Feuillet F, Roquilly A; PACMAN group. PACMAN trial protocol, Perioperative Administration of Corticotherapy on Morbidity and mortality After Non-cardiac major surgery: a randomised, multicentre, double-blind, superiority study. BMJ Open. 2019 Mar 23;9(3):e021262. doi: 10.1136/bmjopen-2017-021262.

  PMID: 30904834 DERIVED

MeSH Terms

Interventions

Dexamethasone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 14, 2017
• Study Start: December 13, 2017
• Primary Completion: April 16, 2019
• Study Completion: April 16, 2019
• Last Updated: June 1, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (29)