PADDI trial: Perioperative ADministration of Dexamethasone and Infection trial

The Perioperative ADministration of Dexamethasone and Infection (PADDI) trial recruited 8880 patients from March 2016 to July 2019 from 55 sites across Australia, New Zealand, Hong Kong and South Africa. The manuscript detailing the trial results is now published in the New England Journal of Medicine. 

We thank all our PADDI trial committee members, site investigators, fellows, trainees, research coordinators and the thousands of patients who were involved in the trial. Their efforts ultimately improve safety and care in the perioperative setting. The PADDI trial was the brainchild of Professor Tomás Corcoran and brings to fruition more than 10 years of concept development and preliminary research in the lead up to the major funding announcement in 2014, when it was awarded the highest valued National Health and Medical Research Council (NHMRC) project grant at that point of time in the history of the scheme.

Every year millions of patients undergo surgery worldwide. Surgical site infections (SSI) occur in up to 12 per cent of these patients. Complications resulting from SSI lead to increased morbidity and mortality, extended hospital stays, and carry an associated cost of up to US$10 billion per annum.

Dexamethasone is widely used by anaesthetists in the perioperative period, principally as an effective antiemetic to prevent postoperative nausea and vomiting (PONV). The molecular mechanisms underlying dexamethasone’s antiemetic action are not fully understood. However, because it is a potent glucocorticosteroid, it has immunosuppressive and hyperglycaemia effects. It is hypothesised that these actions may increase the risk of perioperative infections, particularly in patients with diabetes mellitus, who are already at increased risk of complications. Whether the use of dexamethasone in the perioperative period increases the risk of surgical site and other infections, has not been definitively established. This is an important health priority as in Australia alone up to one million patients will receive dexamethasone as part of their anaesthesia care annually.

This study aims to definitively address the impact of dexamethasone on surgical site infection and will be stratified according to diabetes status.

Study size
8880 adult patients

Study design
Multi-centre prospective, double blind, active control, parallel assessment, stratified, pragmatic non-inferiority safety and efficacy study.

Primary outcome
Surgical site infection within 30 days of surgery.

Secondary outcomes
Secondary outcomes include nausea and vomiting parameters, quality of perioperative analgesia, the incidence of chronic postsurgical pain, length of hospital stay, quality of recovery on days 1 and 30, inflammatory responses, glucose-related outcomes, infections at site other than the surgical site (pneumonia, bloodstream infection, urinary tract infection) up to 30 days, the incidence of sepsis and the incidence of wound dehiscence.

Study population
Adult patients, ASA physical status 1-4, undergoing elective or expedited (non-cardiac) surgery of at least two hours duration, using general anaesthesia with or without regional block, with a single (or multiple) surgical skin incision(s) of >5 cm in length, and a minimum anticipated hospital stay of at least one night.

The Australian National Health and Medical Research Council, Monash University and the Research Grant Council of Hong Kong.

Australian New Zealand Clinical Trials Registry registration number: ACTRN12614001226695

Reade MC, Marks DC, Howe B, McGuinness S, Parke R, Navarra L, Charlewood R, Johnson L, McQuilten Z; CLIP-II and CLIPNZ-II Investigators.; CLIP-II and CLIPNZ-II Investigators. Cryopreserved platelets compared with liquid-stored platelets for the treatment of surgical bleeding: protocol for two multicentre randomised controlled blinded non-inferiority trials (the CLIP-II and CLIPNZ-II trials). BMJ Open. 2022 Dec 20;12(12):e068933. doi: 10.1136/bmjopen-2022-068933. PMID: 36600425; PMCID: PMC9772641.

Flint AWJ, Bailey M, Reid CM, Smith JA, Tran L, Wood EM, McQuilten ZK, Reade MC. Preoperative identification of cardiac surgery patients at risk of receiving a platelet transfusion: The Australian Cardiac Surgery Platelet Transfusion (ACSePT) risk prediction tool. Transfusion. 2020 Oct;60(10):2272-2283. doi: 10.1111/trf.15990. Epub 2020 Aug 5. PMID: 32757209.

Reade MC, Marks DC, Bellomo R, Deans R, Faulke DJ, Fraser JF, Gattas DJ, Holley AD, Irving DO, Johnson L, Pearse BL, Royse AG, Wong J; Cryopreserved vs Liquid Platelet (CLIP) Investigators, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759). Transfusion. 2019 Sep;59(9):2794-2804. doi: 10.1111/trf.15423. Epub 2019 Jul 10. PMID: 31290573.

Reade MC, Marks DC, Johnson L, Irving DO, Holley AD. Frozen platelets for rural Australia: the CLIP trial. Anaesth Intensive Care. 2013 Nov;41(6):804-5. PMID: 24180724.

Dumont LJ, Slichter SJ, Reade MC.Cryopreserved platelets: frozen in a logjam?Transfusion. 2014 Aug;54(8):1907-10. doi: 10.1111/trf.12758. PMID: 25130330.

Johnson L, Reade MC, Hyland RA, Tan S, Marks DC. In vitro comparison of cryopreserved and liquid platelets: potential clinical implications. Transfusion. 2015 Apr;55(4):838-47. doi: 10.1111/trf.12915. Epub 2014 Nov 5. PMID: 25371169.

Marks DC, Johnson L, Reade MC. A clinical trial of frozen platelets: rationale, protocol and pilot analysis plan. Vox Sang.  First published: 22 January 2018.

McGuinness S, Charlewood R, Gilder E, Parke R, Hayes K, Morley S, Al-Ibousi A, Deans R, Howe B, Johnson L, Marks DC, Reade MC; Australian and New Zealand College of Anaesthetists Clinical Trials Network; Australian and New Zealand Intensive Care Society Clinical Trials Group. A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial. Vox Sang. 2022 Mar;117(3):337-345. doi: 10.1111/vox.13203. Epub 2021 Sep 28. PMID: 34581452.

Professor Tomás Corcoran presented the results on 6 May 2021 with panelists Professor Paul Myles, A/Professor Trisha Peel, Professor Allen Cheng and Ms Karen Goulding. The recording of the webinar is now available on YouTube.

Professor Tomás Corcoran and Professor Paul Myles feature in a podcast explaining the PADDI trial and results. Listen here.

Glycaemia substudy of PADDI RCT
PADDI sleep substudy statistical analysis plan