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

This study is not yet open for participant recruitment.
Verified October 2017 by Nantes University Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT03218553
First Posted: July 14, 2017
Last Update Posted: October 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Nantes University Hospital
  Purpose

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.

Hypothesis Patients treated with early continuous hyperosmolar therapy have reduced morbidity and mortality rates compared to those receiving standard care alone after traumatic brain injury.

Perioperative administration of moderate dose of dexamethasone reduces postoperative morbidity and mortality after major non-cardiac surgery.


Condition Intervention Phase
Major Non-cardiac Surgery Drug: Dexamethasone Drug: Placebos Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery : a Randomized, Multicentre, Double Blind, Study

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • 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 [ Time Frame: 14 days ]

Secondary Outcome Measures:
  • All cause mortality [ Time Frame: 28 days ]
  • Hospital free days [ Time Frame: 28 days ]
  • Rate of patients with post operative sepsis [ Time Frame: 28 days ]
  • Postoperative intubation rate for respiratory failure [ Time Frame: 28 days ]
    Postoperative respiratory failure requiring invasive ventilation

  • Rate of patients with postoperative respiratory failure requiring non-invasive ventilation [ Time Frame: 28 days ]
  • Surgical complications [ Time Frame: 28 days ]
    The Clavien-Dindo classification

  • Duration of hospitalization [ Time Frame: 28 days ]
  • Rate of unplanned hospitalization in intensive care unit [ Time Frame: 28 days ]
  • Rate of patients developing postoperative organ failures [ Time Frame: 28 days ]
  • Blood level of marker of inflammation (C Reactive protein) [ Time Frame: 28 days ]
  • Delayed healing defined as non hermetic scar at day 7. [ Time Frame: 28 days ]

Estimated Enrollment: 1222
Anticipated Study Start Date: November 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexamethasone
Standard cares plus postoperative administrations of glucocorticoid
Drug: Dexamethasone
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 Comparator: placebo
Standard cares plus postoperative administrations of placebo
Drug: Placebos
placebo : first infusion at the end of the surgical procedure, second 24 hours after the surgery

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. 1022 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.

Discussion :

The PACMAN trial is the first randomized controlled trial powered to investigate whether perioperative administration of dexamethasone in high risk patients improve outcomes.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03218553


Contacts
Contact: Karim ASEHNOUNE, Pr +33 2 44 76 68 90 karim.asehnoune@chu-nantes.fr
Contact: Antoine ROQUILLY, Dr +33 2 44 78 22 30 antoine.roquilly@chu-nantes.fr

Locations
France
CHU Angers Not yet recruiting
Angers, France, 49933
Contact: Sigismond LASOCKI       silasocki@chu-angers.fr   
Hôpital Jean Verdier Not yet recruiting
Bondy, France, 93140
Contact: Roland Amathieu       roland.amathieu@aphp.fr   
CHU La Cavale Blanche Not yet recruiting
Brest, France, 29609
Contact: Olivier Huet       olivier.huet@chu-brest.fr   
Hôpital Estaing, CHU de Clermont Ferrand Not yet recruiting
Clermont Ferrand, France, 63000
Contact: Emmanuel FUTIER       efutier@chu-clermontferrand.fr   
Hôpital Gabriel Montpied Not yet recruiting
Clermont-Ferrand, France, 63000
Contact: Jean-Etienne BAZIN       jebazin@chu_clermontferrand.fr   
Hôpital Beaujon Not yet recruiting
Clichy, France, 92110
Contact: Catherine Paugram       catherine.paugam@bjn.aphp.fr   
CHD Vendée Not yet recruiting
La Roche-sur-Yon, France, 85000
Contact: Mathieu Oudot       mathieu.oudot@chd-vendee.fr   
Centre Hospitalier Du Mans Not yet recruiting
Le Mans, France, 72037
Contact: Charlene Le Moal       charlene.lemoal@orange.fr   
Hôpital Claude Huriez Not yet recruiting
Lille, France, 59037
Contact: Gilles Lebuffe       gilles.lebuffe@chru-lille.fr   
Hopital Edouard Herriot Not yet recruiting
Lyon, France, 69003
Contact: Thomas Rimmele       thomas.rimmele@chu-lyon.fr   
Institut Paoli Calmettes Not yet recruiting
Marseille, France, 13009
Contact: Marion Faucher         
Hôpital Timone Not yet recruiting
Marseille, France, 13385
Contact: Nicolas Bruder       nicolas.bruder@ap-hm.fr   
Hôpital Nord Not yet recruiting
Marseille, France, 13975
Contact: Marc Leone       marc.leone@ap-hm.fr   
Hôpital Saint-Eloi Not yet recruiting
Montpellier, France, 34295
Contact: Samir Jaber       s-jaber@chu-montpellier.fr   
Clinique Jules Verne Not yet recruiting
Nantes, France, 44000
Contact: Florent Capron       florent.capron@mla.fr   
Le Confluent Not yet recruiting
Nantes, France, 44000
Contact: Jerome Paulus         
Hotel Dieu Nantes Not yet recruiting
Nantes, France, 44093
Contact: karim ASHENOUNE, Pr       karim.asehnoune@chu-nantes.fr   
Contact: Antoine ROQUILLY, Dr       antoine.roquilly@chu-nantes.fr   
Hôpital Laennec Not yet recruiting
Nantes, France, 44093
Contact: Bertrand Rozec       bertrand.rozec@chu-nantes.fr   
C.R.L.C.C. Nantes Atlantique Not yet recruiting
Nantes, France, 44805
Contact: Frederic Simmoneau       Frederic.simmoneau@ico.unicancer.fr   
CHU Carémeau Not yet recruiting
Nîmes, France, 30 000
Contact: Philippe Cuvillon       philippe.cuvillon@chu-nimes.fr   
Hôpital Saint Antoine Not yet recruiting
Paris, France, 75000
Contact: Thomas LESCOT       thomas.lescot@aphp.fr   
Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand Widal Not yet recruiting
Paris, France, 75475
Contact: Benoit Plaud       benoit.plaud@aphp.fr   
CHU Lyon Sud Not yet recruiting
Pierre-Bénite, France, 69310
Contact: Vincent Piriou       vincent.piriou@chu-lyon.fr   
CHU de Poitiers Not yet recruiting
Poitiers, France, 86021
Contact: Bertrand Debaene       b.debaene@chu-poitiers.fr   
Hôpital Robert Debré Not yet recruiting
Reims, France, 51100
Contact: Benny Charbit       bcharbit@chu-reims.fr   
Hôpital Pontchaillou Not yet recruiting
Rennes, France, 35033
Contact: Hélène BELOEIL       helene.beloeil@chu-rennes.fr   
CHU de Rouen Not yet recruiting
Rouen, France, 76031
Contact: Bertrand Dureuil       bertrand.dureuil@chu-rouen.fr   
CHU Saint Etienne Not yet recruiting
Saint-Étienne, France, 42055
Contact: Serge Molliex       serge.molliex@chu-st-etienne.fr   
Nouvel Hôpital Civil Not yet recruiting
Strasbourg, France, 67098
Contact: Julien Pottecher       julien.pottecher@chru-strasbourg.fr   
CHU de Toulouse Not yet recruiting
Toulouse, France, 31059
Contact: Vincent Minville         
Hôpital Pierre-Paul RIQUET Not yet recruiting
Toulouse, France, 31059
Contact: Thomas Geeraerts       geeraerts.t@chu-toulouse.fr   
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Cyrus Motamed       Cyrus.MOTAMED@gustaveroussy.fr   
Sponsors and Collaborators
Nantes University Hospital
  More Information

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT03218553     History of Changes
Other Study ID Numbers: RC17_0029
First Submitted: July 10, 2017
First Posted: July 14, 2017
Last Update Posted: October 23, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Postoperative Complications
Pathologic Processes
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action