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

May 28, 2020 updated by: Nantes University Hospital

Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery : a Randomized, Multicentre, Double Blind, Study

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1222

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933
        • CHU Angers
      • Brest, France, 29609
        • CHU La Cavale Blanche
      • Clermont Ferrand, France, 63000
        • Hôpital Estaing, CHU de Clermont Ferrand
      • Clichy, France, 92110
        • Hôpital Beaujon
      • La Roche-sur-Yon, France, 85000
        • CHD Vendée
      • Le Mans, France, 72037
        • Centre Hospitalier du Mans
      • Lille, France, 59037
        • Hôpital Claude Huriez
      • Lyon, France, 69003
        • Hôpital Edouard Herriot
      • Marseille, France, 13009
        • Institut Paoli Calmettes
      • Marseille, France, 13385
        • Hôpital Timone
      • Marseille, France, 13975
        • Hôpital Nord
      • Montpellier, France, 34295
        • Hopital Saint-Eloi
      • Nantes, France, 44000
        • Clinique Jules Verne
      • Nantes, France, 44000
        • Le Confluent
      • Nantes, France, 44093
        • Hotel Dieu Nantes
      • Nantes, France, 44093
        • Hôpital Laënnec
      • Nantes, France, 44805
        • C.R.L.C.C. Nantes Atlantique
      • Paris, France, 75000
        • Hôpital Saint Antoine
      • Paris, France, 75475
        • Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand Widal
      • Pierre-Bénite, France, 69310
        • CHU Lyon Sud
      • Poitiers, France, 86021
        • CHU de Poitiers
      • Quimper, France, 29107
        • CH Quimper
      • Rennes, France, 35033
        • Hôpital Pontchaillou
      • Rouen, France, 76031
        • CHU de Rouen
      • Saint-Étienne, France, 42055
        • CHU Saint Etienne
      • Strasbourg, France, 67098
        • Nouvel Hôpital Civil
      • Toulouse, France, 31059
        • CHU de Toulouse
      • Valenciennes, France, 59300
        • Ch Valenciennes
      • Villejuif, France, 94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
All cause mortality
Time Frame: 28 days
28 days
ICU length of stay
Time Frame: 28 days
28 days
Hospital free days
Time Frame: 28 days
28 days
Rate of patients with post operative sepsis
Time Frame: 28 days
28 days
Postoperative intubation rate for respiratory failure
Time Frame: 28 days
Postoperative respiratory failure requiring invasive ventilation
28 days
Rate of patients with postoperative respiratory failure requiring non-invasive ventilation
Time Frame: 28 days
28 days
Surgical complications
Time Frame: 28 days
The Clavien-Dindo classification
28 days
Duration of hospitalization
Time Frame: 28 days
28 days
Rate of unplanned hospitalization in intensive care unit
Time Frame: 28 days
28 days
Rate of patients developing postoperative organ failures
Time Frame: 28 days
28 days
Blood level of marker of inflammation (C Reactive protein)
Time Frame: 28 days
28 days
Delayed healing defined as non hermetic scar
Time Frame: 28 days
28 days
Rate of patients with Gastric ulcer
Time Frame: 28 days
28 days
Rate of patients with Digestive bleeding
Time Frame: 28 days
28 days
Rate of patients with Anastomotic leakage
Time Frame: 28 days
28 days
Dose of insulin
Time Frame: 3 days
3 days
Rate of patients with Hypokaliemia (< 4 mmol/l)
Time Frame: 28 days
28 days
Rate of patients with Dysnatremia (<139 mmol/l or > 145 mmol/l)
Time Frame: 28 days
28 days
Rate of patients with Hypocalcemia (<2.2 mmol/l)
Time Frame: 28 days
28 days
Rate of patients with Cardiac events (Atrial fibrillation / cardiac flutter, Acute coronary syndrome or Cardiac failure)
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nantes University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 13, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 16, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 16, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 14, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC17_0029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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