About the ANZCA Clinical Trials Network

Our purpose

Our purpose, as a college, is "to serve our communities by leading high quality care in anaesthesia, perioperative and pain medicine, optimising health and reducing the burden of pain". From this flow three major objectives:

1. To promote professional standards and patient safety in anaesthesia, perioperative medicine and pain medicine. 
2. To promote education in anaesthesia, perioperative medicine and pain medicine.
3. To advance the science and practice of anaesthesia, perioperative medicine and pain medicine.

Our vision

Our vision, as a college, is "to be a recognised world leader in training, education, research, and in setting standards for anaesthesia and pain medicine". The ANZCA CTN has also developed its own vision, "to be a world leader in delivering high quality trial evidence that translates into safe and effective clinical practice in anaesthesia, perioperative and pain medicine.”

Our strategic priorities

In 2021-24, the strategic priorities for the ANZCA CTN will be to deliver:

• High quality evidence through clinical trials to guide safe and effective practice
• A diverse network of outstanding clinical trial leaders, coordinators, investigators and sites
• Engagement with our stakeholders and collaborators
• A sustainable Clinical Trials Network

The ANZCA Clinical Trials Network was born out of the successful collaboration of investigators of the MASTER and the B-Aware trials. The MASTER Anaesthesia Study, led by Associated Professor John Rigg from Western Australia, was the first multicentre randomised controlled trial in anasethesia in Australia to be funded by the National Health and Medical Research Council (NHRMC) in 1997. The trial was published in 2002 in the Lancet which is a testament to the rigour in study design, research quality and scientific merit of the trial. The MASTER trial paved the way for a long successful history in running investigator-led trials in anasethesia, pain and perioperative medicine. 

The ANZCA Trials Group was established in 2003 through a formal collaboration with Monash University's School of Public Health and Epidemiology and ANZCA. The ANZCA Trials Group was the first trials group in Australia established by a medical college. The ANZCA Trials Group changed its name to ANZCA Clinical Trials Network in 2016. The CTN team is now located at the School of Translational Medicine at Monash University within a stone's throw of ANZCA head office in Melbourne. 

More than 57,000 participants have been recruited to our CTN trials since the MASTER trial. We are very grateful for the patients, their relatives and hospital staff for supporting our trials.

Clinical Trials Network investigators are world leaders in clinical trial methodology and delivery, and have been awarded more than $A73 million in competitive research grants. 

The network facilitates large multicentre clinical trials which have been prodominantly funded by the Australian National Health and Medical Research Council (NHMRC), Health Research Council of New Zealand (HRC) and Research Grant Council of Hong Kong, by bringing together experienced trialists, providing infrastructure, and importantly, directly supporting research coordinators at many sites.
 

​The network is supported by the ANZCA Foundation, which has funded many of the exploratory studies through the pilot grants and project grants schemes that have subequently led to investigators securing competitive government grants to run the larger scale clinical trials. These grants have been made possible through the generosity of donors and fellows and we kindly thank all supporters and donors of the ANZCA Foundation. 
 

The MASTER Anaesthesia trial
Epidural anaesthesia and analgesia in major abdominal surgery

Epidural analgesia was widely suggested to improve patient safety in major surgery. 915 high risk non-cardiac surgery patients were randomised to epidural or intravenous analgesia in major abdominal surgery. Epidurals improved quality of analgesia but did not reduce postoperative complications or affect long term cancer surgery outcomes. This led to the much more selective use of epidural analgesia. 

Rigg JR et al. Lancet. 2002.
Number of citations at 14 March 2024: 1390
Funders:  The Australian National Health and Medical Research Council (primary) and the Australian and New Zealand College of Anaesthetists Foundation. 

B-Aware trial
Bispectral index monitoring to prevent awareness during anaesthesia

2,463 non-cardiac surgery patients at risk of awareness randomised to bispectral index monitoring or routine care. Bispectral index monitoring resulted in a reduction in the incidence of awareness compared with routine care. This led to widespread use of this monitoring technology in patients undergoing high risk surgery.

Myles PS et al. Lancet. 2004 
Number of citations at 14 March 2024: 1596

Funders: The Australian and New Zealand College of Anaesthetists Foundation and others. 

ENIGMA trial
Nitrous oxide in patients undergoing major surgery

2,050 non-cardiac surgery patients randomised to nitrous oxide-based or nitrous oxide-free anaesthesia. There was no difference in hospital length of stay in the two groups, but the use of nitrous oxide was associated with more nausea and vomiting, and more pulmonary complications. To definitively investigate the findings further, the ENIGMA-II trial was designed. 

Myles PS et al. Anesthesiology. 2007 
Number of citations at 14 March 2024: 471

Funders: Australian National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists Foundation, and the Health and Health Services Research Fund, Hong Kong, China

POISE trial
Beta blockers in patients undergoing non-cardiac surgery

8,351 non-cardiac surgery patients at risk of perioperative cardiovascular events randomised to metoprolol or placebo (collaboration with the Population Health Research Institute, McMaster University, Canada). Metoprolol reduced the incidence of myocardial infarction but increased the incidence of death and stroke. This led to much more selective use of beta-blockers for cardioprotection by anaesthetists and cardiologists.

POISE Study Group et al. Lancet. 2008.
Number of citations at 14 March 2024: 2547
Funders: The Australian National Health and Medical Research Council, Canadian Institutes of Health Research and others.

The REASON study
Complications and mortality in older surgical patients in Australia and New Zealand

This prospective, observational study of 4158 older patients undergoing non-cardiac surgery found that 20 per cent of patients had a complication within five days of surgery and five per cent died within 30 days. Those with a complication stayed a week longer in hospital, and 14 per cent died within 30 days. This highlighted the urgent need for research into strategies to reduce surgical complications in our ageing population.

Story DA et al. Anaesthesia. 2010.
Number of citations at 14 March 2024: 217
Funder: The Australian and New Zealand College of Anaesthetists Foundation

ENIGMA-II trial
Nitrous oxide anaesthesia and cardiac morbidity after major surgery

7,112 non-cardiac surgery patients at risk of perioperative cardiovascular events randomised to nitrous oxide-based or nitrous oxide-free anaesthesia. There was no difference in the incidence of death, myocardial infarction or any other cardiovascular complication between the two groups.

Myles PS et al. Lancet. 2014
Number of citations at 14 March 2024: 197

Funders: Australian National Health and Medical Research Council (primary); The Australian and New Zealand College of Anaesthetists Foundation and others. 

POISE-II trial
Aspirin and clonidine in patients undergoing non-cardiac surgery

10,010 non-cardiac surgery patients at risk of perioperative cardiovascular events randomised to aspirin or placebo, and clonidine or placebo (collaboration with the Population Health Research Institute, McMaster University, Canada). Aspirin and clonidine did not alter the incidence of death and major cardiovascular complications, but aspirin increased the risk of bleeding and clonidine increased the risk of hypotension.

Clonidine trial
Devereaux PJ et al. N Engl J Med. 2014
Number of citations at 14 March 2024: 397

Aspirin trial
Devereaux PJ et al. N Engl J Med. 2014 
Number of citations at 14 March 2024: 978

Funders: The Australian National Health and Medical Research Council, Canadian Institutes of Health Research and others

ATACAS trial 
Aspirin and Tranexamic acid in patients undergoing coronary-artery surgery

2,100 cardiac surgery patients randomised to aspirin or placebo, and tranexamic acid or placebo. The incidences of death and major cardiovascular complications were similar in the aspirin and placebo patients. 

In 4631 patients having coronary artery surgery randomised to tranexamic acid or placebo, pre-operative tranexamic acid reduced bleeding complications without increasing the risk of death and thrombotic complications within 30 days of surgery. Tranexamic acid was associated with a small increase risk of post-operative seizures. Tranexamic acid can be safely used for coronary artery surgery.

Aspirin results
Myles PS et al. N Engl J Med. 2016 
Number of citations at 14 March 2024: 169

Tranexamic results
Myles PS et al. N Engl J Med. 2017 
Number of citations at 14 March 2024: 553

Funders: The Australian National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists, and the National Institute of Health Research.

GAS trial
General Anaesthesia compared to Spinal anaesthesia trial

The safety of general anaesthesia to the developing brain has been questioned. ANZCA fellows led the GAS study, a multinational randomised controlled trial of general versus spinal anaesthesia for neonatal inguinal hernia repair. At two and five years, there was no difference in neuro-developmental outcomes between the two groups, confirming the safety of general anaesthesia in young children.

Two year outcome results
Davidson AJ et al. Lancet. 2016
Number of citations at 14 March 2024: 853

Five year outcome results
McCann ME et al. Lancet. 2019 
Number of citations at 14 March 2024: 517 (5 year outcome)

Funders: US National Institutes of Health, Australian National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists Foundation and many others.

RELIEF
Restrictive versus liberal fluid therapy in major abdominal surgery

Restrictive administration of intravenous fluids has been widely recommended to reduce complications in bowel surgery. 3000 high-risk abdominal surgery patients were randomised to restrictive or liberal intravenous fluids. Restrictive fluids led to increased rates of kidney failure postoperatively, and possibly of wound infection. This trial is dramatically altering standard anaesthesia practice. 

Myles PS et al. N Engl J Med. 2018 
Number of citations at 14 March 2024: 619

Funders: The Australian National Health and Medical Research Council (NHMRC), the Australian and New Zealand College of Anaesthetists Foundation (pilot study), Monash University,  the Health Research Council of New Zealand, and the United Kingdom National Institute of Health Research.

Balanced Anaesthesia Study
Anaesthetic depth and complications in major surgery

Deeper anaesthesia has been associated with poorer postoperative outcomes. 6500 high-risk elderly patients were randomised to deep (bispectral index = 35) or light (bispectral index = 50) general anaesthesia. There was no effect of anaesthetic depth on the primary outcome of one-year mortality, providing reassurance that deeper anaesthesia is safe.

Short TG et al. Lancet. 2019 
Number of citations at 14 March 2024: 131

Funders: Health Research Council of New Zealand, the Australian National Health and Medical Research Council, the Research Grants Council of Hong Kong, the National Institute for Health and Research in the UK (portfolio status), the National Institutes of Health in the USA, and the Australian and New Zealand College of Anaesthetists Foundation (pilot study).

PADDI
Perioperative ADministration of Dexamethasone and Infection trial

Dexamethasone is widely administered to prevent postoperative nausea and vomiting, but its potential immunosuppressive properties make its safety unclear. 8,800 non-cardiac surgery patients randomised to dexamethasone 8 mg or placebo. The results showed that administering a low-dose of dexamethasone during anaesthesia for surgical operations does not increase the risk of surgical site infections at 30 days. 

Corcoran TB et. N Engl J Med. 2021 
Number of citations at 17 March 2024: 77

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

POISE-III
Tranexamic acid and hypotension-avoidance in major noncardiac surgery

9535 noncardiac surgery patients at risk of bleeding or blood vessel complications were randomised to receive tranexamic acid or placebo. The incidence of the composite bleeding complications was significantly lower with tranexamic acid than with placebo, however, the noninferiority of tranexamic acid was not established for the cardiovascular outcome (blood clots, heart attack, stroke, or other major blood vessel complications) in the 30 days after surgery.

Devereaux PJ et al. N Engl J Med. 2022 
Number of citations at 24 March 2024: 151

Funders: Canadian Institutes of Health Research, Australian National Health and Medical Research Council and others.

DECIDE Study
Dexmedetomidine in Cardiac surgical Intraoperative Drug Evaluation (DECIDE) study is a triple blind, placebo-controlled, randomised trial (RCT) that will provide definitive, high-quality evidence on whether DEX reduces delirium, improves days alive and at home and preserves one-year cognitive outcomes in 1100 patients undergoing heart surgery.

Funder: The Australian National Health and Medical Research Council 

SNaPP Study
The Sugammadex, neostigmine and postoperative pulmonary complications 
The SNaPP Study is a large (n=3,500) four year, multicentre, double-blind, randomised clinical trial examining the effect of reversal of neuromuscular blockade on postoperative outcomes.

Adult patients having abdominal or thoracic surgery under relaxant general anaesthesia with an endotracheal tube will be randomised to sugammadex or neostigmine for reversal of neuromuscular blockade. The primary outcome is a composite of death or postoperative pulmonary complications up to hospital discharge (or postoperative day 7 if still in hospital).

Funders: Medical Research Future Fund grant and the Australian and New Zealand College of Anaesthetists Foundation (feasbility study). 


HAMSTER
High-Flow Oxygen for Children’s Airway Surgery

The HAMSTER trial is a multi-centre project investigating the role of high-flow during upper airway surgery in 530 children. The primary outcome for the study is the incidence of rescue oxygenation attempts for hypoxaemic events during tubeless airway surgery comparing high flow nasal oxygen to low flow oxygen.

Funders: Society for Paediatric Anaesthesia in New Zealand and Australia, the Australian and New Zealand College of Anaesthetists Foundation and Thrasher Research Foundation


ROCKet
Reduction Of Chronic Post-surgical Pain with Ketamine

​Chronic pain is a common and under-recognised complication of surgery. 4000 patients will be randomised to determine if intravenous ketamine, when given for up to 72 hours prior to and following surgery, reduce the incidence of chronic post-surgical pain reported at 12 months. 

Funders: The Australian National Health and Medical Research Council and the Australian and New Zealand College of Anaesthetists Foundation (pilot study)

ITACS
IV iron for Treatment of Anaemia before Cardiac Surgery

1000 high-risk cardiac surgery patients with preoperative anaemia will be randomised to IV iron infusion or placebo, to see if it reduces need for blood transfusion, complications and days alive and out of hospital up to 90 days after surgery.

Funders: The Australian National Health and Medical Research Council.

VAPOR-C
Volatile Anaesthesia and Perioperative Outcomes Related to Cancer

It is suggested that general anaesthetic gases may suppress immune response and increase risk of tumour recurrence in cancer surgery. 3500 cancer surgery patients will be randomised to intravenous or inhalational anaesthesia, as well as IV lignocaine or placebo. This trial is designed to test for superiority in disease free survival (DFS) of propofol (total intravenous anaesthesia -TIVA) over sevoflurane (inhalational volatile anaesthesia), and intravenous lidocaine over no lidocaine in patients undergoing surgery for colorectal or non small cell lung cancer (NSCLC). 

Funders: The Australian National Health and Medical Research Council, Victorian Comprehensive Cancer Centre and the Australian and the New Zealand College of Anaesthetists Foundation (feasibility study). 

DECS-II
Dexamethasone for Cardiac Surgery-II

2800 patients undergoing cardiac surgery are randomised to receive high dose Dexamethasone or placebo to assess its potential effects 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.

MASTERSTROKE

Management of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischaemic STROKE

Endovascular thrombectomy is an exciting new therapy in acute ischaemic stroke, but little is known about how these patients should best be managed physiologically during the procedure. MASTERSTROKE is a 550 patient study looking at the role of induced hypertension during the ischaemic phase of the procedure on functional recovery at three months.

Funders: Auckland District Health Board Research Trust; The Auckland Medical Research Foundation; the Neurological Foundation of New Zealand, and; the Australian and New Zealand College of Anaesthetists Foundation (pilot study). 

TRIGS
Tranexamic acid and surgical site infection in gastrointestinal surgery

Tranexamic acid (TXA) has been shown to reduce bleeding risk in surgery, but may also promote immune response and reduce infection risk. 3330 patients having gastrointestinal surgery greater than two hours will be randomised to TXA or placebo to determine its effect on risk of surgical site infection to day 30.

Funder: The Australian National Health and Medical Research Council

T-REX trial
Neurodevelopmental outcome after standard dose sevoflurane versus low-dose sevoflurane/ dexmedetomidine/remifentanil anaesthesia in young children​.

The aim of the T-REX trial is to determine if low-dose sevoflurane/dexmedetomidine/ remifentanil anaesthesia is associated with superior neurodevelopmental outcome, compared to standard-dose sevoflurane anaesthesia, in 450 children less than two years of age, having anaesthesia expected to last two hours or longer.

Funders: The Australian National Health and Medical Research Council and IARS SmartTots Research Award (US).

TRICS-IV
Liberal versus restrictive transfusion strategy for cardiac surgery

The TRICS IV trial is designed to determine whether a liberal transfusion strategy is superior to a restrictive strategy in 1440 cardiac patients < 65 years. 
Hypothesis:  A higher haemoglobin (Hb) concentration for red blood cell (RBC) transfusion (liberal transfusion strategy) will be superior to a restrictive strategy in terms of vital organ function (heart, brain and kidney) and mortality six months after cardiac surgery.

Funder: Medical Research Future Fund to run the Australian arm

NATO study
Non-Anaemic iron deficiency and Treatment Outcomes after colorectal cancer surgery

The NATO study is a prospective observational study performed in patients undergoing surgery for colorectal cancer, comparing non-anaemic patients with iron deficiency to those who are iron replete. The primary outcome is days alive and out of hospital at postoperative day 90, with important secondary outcomes examining incidence of postoperative complications, readmission and quality of life. 

Funders: A variety of government, public, private and industry funders.

Chewy study
Chewing gum versus ondansetron for post-operative nausea and vomiting in women and girls having laparoscopic or breast surgery

The Chewy Trial is a multicentre, randomised, controlled trial of chewing gum versus ondansetron for post-operative nausea and vomiting in women and girls having laparoscopic or breast surgery.
Hypothesis: Chewing gum is non inferior to ondansetron in achieving complete cessation of nausea, retching and vomiting postoperatively, within two hours of administration, with no recurrence of nausea and no need for rescue medication.

Funder: The Australian and New Zealand College of Anaesthetists Foundation.

LOLIPOP 
The Long-term Outcomes of Lidocaine Infusions for persistent PostOperative Pain in patients undergoing breast cancer surgery.

The LOLIPOP trial is a large (n=4300) pragmatic, multicentre, randomised, stratified, controlled, superiority trial evaluating the effect of lidocaine infusions in the intra- and postoperative periods on the incidence of moderate or severe chronic post-surgical pain (CPSP) at one year in patients undergoing unilateral elective breast cancer surgery.

Funders: Medical Research Future Fund grant and the Australian and New Zealand College of Anaesthetists Foundation (feasbility study). 

CALIPSO
The Duration of Cardiac Antimicrobial Prophylaxis Outcomes Study

CALIPSO is a large (n=9,180) five year, multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial examining the optimal duration of antibiotic therapy to prevent infections in patients undergoing cardiac surgery.

The trial aims to compare the incidence of surgical site infection (and other healthcare associated infections), health economic and microbiological impact after intraoperative only (Arm A), to 24 hours (Arm B) and, to 48 hours (Arm C) of IV cefazolin and placebo postoperative surgical antimicrobial prophylaxis.

Funder: Medical Research Future Fund

CLIP-II
The cryopreserved vs liquid platelets trial for surgical bleeding

This is a definitive trial to determine if cryopreserved platelets are as safe and effective as liquid-stored platelets in high-risk adult cardiac surgery patients. 808 patients will be randomised to achieve 202 patients transfused platelets (101 in each group). Primary outcome: Volume of post-surgical bleeding in the first 24 hours from the time of ICU admission.

Funder: The Australian National Health and Medical Research Council and the Australian and New Zealand College of Anaesthetists Foundation (feasbility study).