We plan to conduct a large, pragmatic, multicentre, randomised non-inferiority trial to determine whether the use of intraoperative dexamethasone, a widely used antiemetic in perioperative medicine, is associated with an unacceptable increased risk…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Surgical Site Infection at 30 days
Secondary outcome
PONV OUTCOMES
1. Nausea (0-24 hours)- Nausea as measured on a numerical rating scale (NRS) in
the first 24 hours following surgery
2. Vomiting (0-24 hours)- Vomiting (occurrence and number of events) within
first 24hours following surgery
PAIN OUTCOMES
3. Highest pain score (NRS) at rest and on movement in the first 24 hours
4. Chronic Post-Surgical Pain (at 6 months)- defined as pain over the surgical
site, for at least three months after surgery, that cannot be explained by
other causes, such as disease recurrence or a pre-existing pain syndrome.
OTHER OUTCOMES
5. Hospital stay: from the start (date, time) of surgery until actual hospital
discharge.
6. Quality of recovery: QoR-15 score on days 1, and 30
7. C-reactive protein (CRP) concentration- Days 1 and 2 postop.
8. Proportion of patients requiring insulin
9. Hypoglycaemia rates
10. Hyperglycaemic rates
11. Other infections (i.e. non-SSI) at 30 days - see *Infections Diagnostic
Definitions*
12. Sepsis- see *Infections Diagnostic Definitions*
13. Wound Dehiscence- partial or total disruption of any or all layers of the
operative wound.
14. The relationship between diabetic status, glycaemic parameters
(preoperative blood glucose, glycated haemoglobin (HbA1c)) and infective
outcomes
Background summary
Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory and
metabolic effects. It is frequently administered in the perioperative period,
most commonly for prophylaxis and treatment of postoperative nausea and
vomiting (PONV). The growing concern about the routine administration of
dexamethasone in the perioperative period is due to a lack of safety data in
relation to infection risk, particularly in vulnerable populations such as
patients with diabetes and children. Proposed mechanisms of infective risk
include a) the potential for immunosuppression, b) the theoretical impairment
of wound healing and c) induced hyperglycaemia. Any or all of these may
contribute to an increased risk of perioperative infection.
Study objective
We plan to conduct a large, pragmatic, multicentre, randomised non-inferiority
trial to determine whether the use of intraoperative dexamethasone, a widely
used antiemetic in perioperative medicine, is associated with an unacceptable
increased risk (2%) of postoperative infection in 8880 adult surgical
patients. There is biological plausibility that dexamethasone may alter our
defined primary and secondary outcomes (see below). The trial has been endorsed
by the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical
Trials Network and the Australian Society for Infectious Diseases Clinical
Research Network, representing the first collaboration between these two
organizations
Study design
International, multicentre, prospective, randomised, double blind,
placebo-control, parallel assessment, stratified, non-inferiority safety and
effectiveness study.
Intervention
Patients will be randomised to receive dexamethasone 8 mg or saline placebo,
administered intravenously within 5 minutes after induction of anaesthesia.
Study burden and risks
The intervention in this trial is a common prophylactic intervention to prevent
postoperative nausea and vomiting following general anaesthesia. In daily
clinical practice, whether or not this intervention is used depends on the
attending anaesthetist, and varies between anaesthetists. The risks of
participation in this trial is therefore not different from that of other
patients undergoing a surgical procedure.
The burden for the participants consists of 4 blood samples (most of these are
taken regardless within the context of routine care), and the completion of a
number of short questionnaires: once before the operation, and on 2 occasions
in the 6 months following the operation.
Commercial Road 55
Melbourne 3004
AU
Commercial Road 55
Melbourne 3004
AU
Listed location countries
Age
Inclusion criteria
* Adult patients *18 years of age
* American Society of Anesthesiologists (ASA) physical status 1-4
* Elective or Expedited non-cardiac surgery of at least 2 hours duration under general anaesthesia (± regional block)
* At least two hours* duration
* Requiring a hospital stay of at least one postoperative night
* A surgical skin incision > 5 cm in length or multiple incisions with a total incision length of 5 cm.
Exclusion criteria
* Poorly controlled type 1 diabetes (HbA1c > 9.0%)
* Endovascular procedure with a small (< 5 cm length) skin incision
* Ophthalmic surgery
* Planned dexamethasone (or other corticosteroid) therapy ( e.g. history of intractable PONV, maxillofacial surgery, intracranial neurosurgery)
* Recent (< 2 weeks since end of treatment) infective episode requiring treatment with antibiotics
* Chronic antibiotic therapy (e.g. for bronchiectasis, cystic fibrosis etc)
* When surgery is indicated for an infective process (e.g. infected joint prosthesis)
* A history of allergy or adverse reaction to glucocorticoids
* Planned postoperative intubation or ventilation
* Concurrent immunosuppressive therapies
* Current or recent (within preceding 1 month) systemic use of glucocorticoids
* Surgical procedures within the preceding 2 months
* Known immunosuppressed state
* Known moderate or severe liver disease (Hepatitis A, B, C, with cirrhotic liver states, primary biliary cirrhosis, sclerosing cholangitis - any of these with portal hypertension and/or variceal bleeding)
* Dialysis-dependent renal failure
* When the index surgical procedure is expected to require a further surgical procedure within the subsequent 30 days.
* Metastatic cancer
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | ACTRN12614001226695 |
| EudraCT | EUCTR2016-003431-37-NL |
| CCMO | NL58984.041.17 |