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

Evaluation of Dexamethasone in Cardiac Surgery Using a Novel Trial Design

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Response
• Intervention / Treatment: Drug: Dexamethasone

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".

• Study Type: Interventional
• Enrollment (Actual): 1956
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
days at home up to 30 days after 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).	30 days from Start of Surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
respiratory failure	Uninterrupted postoperative mechanical ventilation for more than 48 hours from admission to ICU	30 days from Start of Surgery
Infection	Surgical site infection, pneumonia, or documented positive microbial culture from any site (including blood).	30 days from Start of Surgery
Myocardial Infarction	Postoperative myocardial infarction will be defined according to the third universal definition	30 days from Start of Surgery
Stroke	A new neurological deficit lasting more than 24 hours or leading to earlier death, and confirmed by medical imaging.	30 days from Start of Surgery
Peak blood glucose	The highest blood glucose measured in this same period	30 days from Start of Surgery
Length of stay	Time from postoperative ICU admission to ICU discharge (hours) and hospital discharge (days).	30 days from Start of Surgery
Quick SOFA score	Tachypnoea, altered mentation and/or hypotension	Each evening on days 1-3 after surgery

Collaborators and Investigators

• Sponsor: Bayside Health
• Collaborators: UMC Utrecht
• Investigators: Principal Investigator: Paul S Myles, MBBS, MD, Alfred Hospital, Monash University

Publications and helpful links

General Publications

• Myles PS, Dieleman JM, Forbes A, Heritier S, Smith JA. Dexamethasone for Cardiac Surgery trial (DECS-II): Rationale and a novel, practice preference-randomized consent design. Am Heart J. 2018 Oct;204:52-57. doi: 10.1016/j.ahj.2018.06.008. Epub 2018 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: December 21, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: cardiac surgery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 69

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