Dexamethasone for Cardiac Surgery-II Trial

Inflammatory Response Clinical Trial

— DECS-II  

Official title:

Evaluation of Dexamethasone in Cardiac Surgery Using a Novel Trial Design

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03002259
• Other study ID #: 69
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 1, 2018
• Est. completion date: January 31, 2023

Study information

• Verified date: January 2023
• Source: Bayside Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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".

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1956
• Est. completion date: January 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Response

Intervention

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.

Locations

Country	Name	City	State
Australia	Alfred Health	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Bayside Health	UMC Utrecht

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	respiratory failure	Uninterrupted postoperative mechanical ventilation for more than 48 hours from admission to ICU	30 days from Start of Surgery
Secondary	Infection	Surgical site infection, pneumonia, or documented positive microbial culture from any site (including blood).	30 days from Start of Surgery
Secondary	Myocardial Infarction	Postoperative myocardial infarction will be defined according to the third universal definition	30 days from Start of Surgery
Secondary	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
Secondary	Peak blood glucose	The highest blood glucose measured in this same period	30 days from Start of Surgery
Secondary	Length of stay	Time from postoperative ICU admission to ICU discharge (hours) and hospital discharge (days).	30 days from Start of Surgery
Secondary	Quick SOFA score	Tachypnoea, altered mentation and/or hypotension	Each evening on days 1-3 after surgery