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Dexamethasone for Cardiac Surgery-II Trial (DECS-II)

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ClinicalTrials.gov Identifier: NCT03002259
Recruitment Status : Recruiting
First Posted : December 23, 2016
Last Update Posted : October 12, 2020
Sponsor:
Collaborator:
UMC Utrecht
Information provided by (Responsible Party):
Bayside Health

Brief Summary:

Background. Numerous studies have investigated high-dose corticosteroids in cardiac surgery, but with mixed results leading to ongoing variations in practice around the world. The Dexamethasone for Cardiac Surgery-II Trial (DECS-II) is a study comparing high-dose dexamethasone with placebo in patients undergoing cardiac surgery.

Methods. We discuss the rationale for conducting DECS-II, a 2800-patient, pragmatic, multicenter, assessor-blinded, randomized trial in cardiac surgery, and the features of the DECS-II study design (objectives, end points, target population, balanced clusters based on practice preference with post-randomization consent, treatments, patient follow-up and analysis).

Conclusions. The DECS-II Trial will use a novel, efficient trial design to evaluate whether high-dose dexamethasone has a patient-centered benefit of enhancing recovery and increasing the number of days at home after cardiac surgery.


Condition or disease Intervention/treatment Phase
Inflammatory Response Drug: Dexamethasone Phase 4

Detailed Description:

High-dose corticosteroids attenuate the inflammatory response to surgery with CPB and are commonly used in some countries,but uncommonly in the US, Canada and Australia. Steroids can reliably attenuate activation of the complement pathways associated with cardiac surgery, but clinical trials have had mixed results. The current evidence is dominated by the results of two recent large randomized trials: DECS (n=4,494)6 and SIRS (n=7,507).

Both DECS and SIRS assigned patients undergoing cardiac surgery with CPB to receive either a high intraoperative dose of steroids (dexamethasone 1 mg/kg, or methylprednisolone 500 mg, respectively) or placebo. The point estimates of both trials suggested a possible reduction in serious complications and mortality. Planned subgroup analyses in the DECS trial steroids reduced the incidence of respiratory failure (3.0 % vs. 4.3%, P=0.02), infection (9.5% vs. 14.8%, P=0.009), and shortened hospital stay (median 8 [7-13] vs. 9 [7-13] days, P=0.009).6 Severe renal failure (need for RRT) was reduced, 0.4% vs. 1.0%, P=0.04.8 But SIRS found methylprednisolone was associated with a higher incidence of myocardial injury (as measured by elevation of CK-MB enzyme). Nether trial identified a higher risk of myocardial infarction (MI). The methylprednisolone-induced elevation of CK-MB may therefore be a class effect.

Another compelling finding in pre-planned subgroup analysis of patient age groups is that when limiting analysis to those aged less than 75 years in the DECS trial, dexamethasone reduced the risk of the primary composite endpoint, RR 0.74 (95% CI: 0.58-0.95), P=0.017; as well as respiratory failure RR 0.62 (95% CI: 0.42-0.91), P=0.014; and possibly mortality RR 0.53 (95% CI: 0.26-1.10), P=0.08.6 This age-interaction effect is supported by the demonstration of increased C-reactive protein concentrations in younger patients enrolled in the DECS trial.

Therefore, it is highly plausible that prophylactic steroids can suppress deregulated inflammation and thus improve outcomes in cardiac surgery, but only when used in a less elderly (i.e. <75 years) patient population.

In retrospect, the primary endpoints of both DECS and SIRS trials can be challenged, in that they used composites heavily weighted by thrombotic events (MI, stroke) and not specific to inflammation (respiratory failure, kidney injury, sepsis, prolonged ICU and hospital stay, mortality). We thus plan to re-evaluate dexamethasone in cardiac surgery, using a patient-centred, clinically important endpoint focused on enhanced recovery and earlier hospital discharge: "days alive and at home up to 30 days after surgery".

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Dexamethasone in Cardiac Surgery Using a Novel Trial Design
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
No Intervention: Control
No placebo required
Active Comparator: Dexamethasone
Dexamethasone, 1 mg/kg (maximal dose 100 mg), single dose administration before cardiopulmonary bypass
Drug: Dexamethasone
Dexamethasone administered as a single IV injection after induction of anaesthesia, but before initiation of CPB. Prepare as a 20 mg/mL dexamethasone solution, made up with 0.9% saline to 10 ml.




Primary Outcome Measures :
  1. days at home up to 30 days after surgery [ Time Frame: 30 days from Start of Surgery ]
    Home is defined as a person's usual abode or that of a close relative, excluding any nursing facility (rehabilitation center or nursing home).


Secondary Outcome Measures :
  1. respiratory failure [ Time Frame: 30 days from Start of Surgery ]
    Uninterrupted postoperative mechanical ventilation for more than 48 hours from admission to ICU

  2. Infection [ Time Frame: 30 days from Start of Surgery ]
    Surgical site infection, pneumonia, or documented positive microbial culture from any site (including blood).

  3. Myocardial Infarction [ Time Frame: 30 days from Start of Surgery ]
    Postoperative myocardial infarction will be defined according to the third universal definition

  4. Stroke [ Time Frame: 30 days from Start of Surgery ]
    A new neurological deficit lasting more than 24 hours or leading to earlier death, and confirmed by medical imaging.

  5. Peak blood glucose [ Time Frame: 30 days from Start of Surgery ]
    The highest blood glucose measured in this same period

  6. Length of stay [ Time Frame: 30 days from Start of Surgery ]
    Time from postoperative ICU admission to ICU discharge (hours) and hospital discharge (days).

  7. Quick SOFA score [ Time Frame: Each evening on days 1-3 after surgery ]
    Tachypnoea, altered mentation and/or hypotension



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females, age 18 to 75 years undergoing elective cardiac surgery with cardiopulmonary bypass
  2. EuroScore-II estimated risk of 1.5% or higher

Exclusion Criteria:

  1. Poor language (English or Dutch) comprehension
  2. Type I diabetes
  3. Endocarditis or other evidence of sepsis
  4. Preoperative steroid therapy

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): NCT03002259


Contacts
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Contact: Paul S Myles, MBBS, MD +61390762000 p.myles@alfred.org.au
Contact: Sophie K Wallace, MPH =61390762651 ext 2651 s.wallace@alfred.org.au

Locations
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Australia, Victoria
Alfred Health Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Paul S Myles, MD    61390763176    p.myles@alfred.org.au   
Contact: Sophie K Wallace, MPH    61390762651    s.wallace@alfred.org.au   
Sponsors and Collaborators
Bayside Health
UMC Utrecht
Investigators
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Principal Investigator: Paul S Myles, MBBS, MD Alfred Hospital, Monash University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bayside Health
ClinicalTrials.gov Identifier: NCT03002259    
Other Study ID Numbers: 69
First Posted: December 23, 2016    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayside Health:
cardiac surgery
Additional relevant MeSH terms:
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Dexamethasone
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