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Trial registered on ANZCTR


Registration number
ACTRN12614001226695
Ethics application status
Approved
Date submitted
7/11/2014
Date registered
21/11/2014
Date last updated
4/06/2019
Date data sharing statement initially provided
4/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Perioperative ADministration of Dexamethasone and Infection - The PADDI Trial
Scientific title
The effect in diabetic and non-diabetic surgical patients of the administration of dexamethasone on surgical site infections
Secondary ID [1] 285611 0
Nil
Universal Trial Number (UTN)
U1111-1163-8271
Trial acronym
PADDI Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus 293461 0
Perioperative Infective Complications 293462 0
Surgery 293463 0
Condition category
Condition code
Anaesthesiology 293741 293741 0 0
Anaesthetics
Metabolic and Endocrine 293830 293830 0 0
Diabetes
Infection 293831 293831 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dexamethasone 8mg intravenously administered immediately following the induction of anaesthesia
Intervention code [1] 290567 0
Treatment: Drugs
Intervention code [2] 290635 0
Prevention
Comparator / control treatment
Placebo (intravenous saline)
Control group
Placebo

Outcomes
Primary outcome [1] 293542 0
Surgical Site Infection- CDC definitions
Timepoint [1] 293542 0
30 days postoperatively
Secondary outcome [1] 371153 0
1. Superficial, deep and organ space infections within 30 days, considered separately. This endpoint is assessed through phone follow up with patient regarding signs and symptoms followed by medical record review / surgical review notes/ GP review.
Timepoint [1] 371153 0
30 days postoperatively
Secondary outcome [2] 371154 0
2. Surgical site infection (as per the primary endpoint definition) including deep and organ space infections occurring within 90 days in patients receiving prosthetic material during surgery. This endpoint is assessed through phone follow up with patient regarding signs and symptoms followed by medical record review / surgical review notes/ GP review.
Timepoint [2] 371154 0
90 days postoperatively
Secondary outcome [3] 371155 0
3. Other infections (composite including urinary tract infections, pneumonia and catheter related infections) and sepsis (All of these will comply with CDC criteria for definition of infections at each site).
This endpoint is assessed through phone follow up with patient regarding signs and symptoms followed by medical record review / surgical review notes/ GP review.
Timepoint [3] 371155 0
30 days postoperatively
Secondary outcome [4] 371156 0
4. Quality of recovery: QoR-15 score on days 1 and 30
Timepoint [4] 371156 0
Post-op Day 1 and Day 30
Secondary outcome [5] 371157 0
5. Chronic Post-Surgical Pain (CPSP) (at 6 months) - will be defined as pain reported by the patient at the six month follow up, in the area of the index surgery which was not present prior to surgery.
Patient reported outcome based on validated questionnaires - Neuropathic Pain Questionnaire and the mBPI Modified Brief Pain Inventory..
Timepoint [5] 371157 0
6 Months postoperatively
Secondary outcome [6] 371158 0
6. Death or new onset disability within 6 months following surgery. Defined as a 4-point (8%) or greater increase in the 12-item WHODAS 2.0 score at both 30 days and 6 months compared with baseline (preoperative) score.
Timepoint [6] 371158 0
Day 30 and 6 month postoperatively
Secondary outcome [7] 371159 0
T1. Nausea (0-24 hours) - Worst nausea as measured on a numerical rating scale (numerical rating scale[NRS], 0-10) in PACU; in the first 24 hours following surgery and post-PACU, on day 2, and on day 3. Antiemetic usage in each of these periods.
Timepoint [7] 371159 0
Postoperative Days 1, 2, 3
Secondary outcome [8] 371160 0
T2. Vomiting (0-24 hours)- Vomiting (occurrence and number of events) in PACU and within first 24hours following surgery post-PACU, on day 2 and on day 3. Antiemetic usage in each of these periods - this is composite.
This is assessed by medical record review as well as face-to-face patient follow up by research staff at hospitals.
Timepoint [8] 371160 0
Postoperative Days 1, 2, 3
Secondary outcome [9] 371161 0
T3. Highest pain score (NRS, 0-10) at rest and on movement in PACU and in the first 24 hours post-PACU
Timepoint [9] 371161 0
Postoperative Day 1
Secondary outcome [10] 371162 0
T4. Hospital stay: from the start (date, time) of surgery until hospital discharge.
Based on medical record review.
Timepoint [10] 371162 0
Postoperative Day 30 / 6 Months
Secondary outcome [11] 371163 0
T5. CRP concentration - day 2 postop.
Based on pathology test results of serum assay - if patient is still in hospital.
Timepoint [11] 371163 0
Postoperative Day 2
Secondary outcome [12] 371164 0
T6. Glycemic control (defined as the maximal changes in perioperative blood glucose from baseline up to day 2 postoperatively, and the influence of HbA1c value on this change in both strata)
Timepoint [12] 371164 0
Postoperative Day 2 / Day of discharge
Secondary outcome [13] 371165 0
T7. Hypoglycaemic event rates- a hypoglycaemic event being defined as a blood glucose recording less than 4.0 mmol / L.
Timepoint [13] 371165 0
Postoperative up to Day of Discharge
Secondary outcome [14] 371166 0
T8. Hyperglycaemic event rates in patients without diabetes- a hyperglycaemic event being defined as a blood glucose recording greater than 10 mmol / L.
Timepoint [14] 371166 0
Postoperative up to Day of Discharge
Secondary outcome [15] 371167 0
T9. Insulin use rates in patients without diabetes
Based on medical record review of medication administration charts.
Timepoint [15] 371167 0
Postoperative up to Day of Discharge
Secondary outcome [16] 371168 0
T10. Lymphocyte and neutrophil levels- Change in neutrophil-to-lymphocyte ratios from baseline to days 1 and 2
Based on pathology tests - serum assay - conducted whilst patient in hospital
Timepoint [16] 371168 0
Baseline to Postoperative Day 1 and Day 2
Secondary outcome [17] 371169 0
T11. Rates of safety outcomes (unexpected reoperation, unplanned readmission to hospital, myocardial infarction, cerebrovascular accident, deep venous thrombosis, pulmonary embolism, mortality at 30 days and mortality at 6 months), serious adverse events, and severity of adverse events (mild, moderate, severe), classified by organ system
Timepoint [17] 371169 0
Postoperative Day 30 and 6 Months

Eligibility
Key inclusion criteria
Adult patients >18 years of age
ASA grade 1-4 (changed to 2-4 in December 2018)
Elective or expedited non-cardiac surgery of at least 2 hours duration under general anaesthesia +/- regional block
Requiring a hospital stay of at least one postoperative night
Surgical skin incision of >5 cm in length or multiple incisions with a total incision length of >5cm
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Poorly controlled 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
• Pregnant and lactating women

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Online randomisation through database
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomisation according to research centre (hospital) and diabetic status ( diabetic and non-diabetic)
Block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Non-inferiority
Phase
Phase 4
Type of endpoint(s)
Safety
Statistical methods / analysis
For this non-inferiority trial, the null hypothesis is stated as- HO: p2 - p1 > delta (inferior); where p1 is the overall proportion of participants expected to experience the outcome if the treatments are non-inferior, and delta is the smallest change in proportions between groups (p2 - p1) which would still be clinically important (delta = 2%)- non-inferiority limit. The maximum size of delta of 2% was agreed adopting the Delphic principle of agreement amongst clinical experts. An absolute increase in risk of infection of 2% produces a number needed to harm (NNH) of 50. This was considered the maximum acceptable increase in infection that could be permitted to conclude non-inferiority. The sample size calculation is based primarily on our own data and other published studies. With an infection rate of 9%, 4303 patients per intervention arm are required to detect the non-inferiority margin of 2% with 90% probability (power), where non-inferiority is concluded if the upper endpoint of the two-sided 95% confidence interval for the difference in infection rates is less than 2%. As recommended, intention to treat (ITT), per protocol (PP) and as treated (AT) analyses will be performed as ITT analysis is typically anticonservative in non-inferiority trials. Target recruitment will be set at 8880 to account for 2% losses to follow up.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 3128 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 11865 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 11866 0
The Alfred - Prahran
Recruitment hospital [4] 11867 0
Dandenong Hospital - Dandenong
Recruitment hospital [5] 11868 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [6] 11869 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [7] 11870 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [8] 11871 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [9] 11872 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [10] 11873 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [11] 11874 0
Blacktown Hospital - Blacktown
Recruitment hospital [12] 11875 0
Westmead Hospital - Westmead
Recruitment hospital [13] 11876 0
Epworth Richmond - Richmond
Recruitment hospital [14] 11877 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [15] 11878 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [16] 11879 0
Western Hospital - Footscray - Footscray
Recruitment hospital [17] 11880 0
Gold Coast University Hospital - Southport
Recruitment hospital [18] 11881 0
Concord Repatriation Hospital - Concord
Recruitment hospital [19] 11882 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [20] 11883 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [21] 11884 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [22] 11885 0
The Northern Hospital - Epping
Recruitment hospital [23] 11886 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [24] 11887 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [25] 11888 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [26] 11889 0
Royal Hobart Hospital - Hobart
Recruitment hospital [27] 11890 0
Wollongong Hospital - Wollongong
Recruitment hospital [28] 11891 0
St John of God Hospital, Ballarat - Ballarat
Recruitment hospital [29] 11892 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [30] 11893 0
Rockingham General Hospital - Cooloongup
Recruitment hospital [31] 11894 0
Wagga Wagga Base Hospital - Wagga Wagga
Recruitment hospital [32] 11895 0
Canterbury Hospital - Campsie
Recruitment hospital [33] 11896 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [34] 11897 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [35] 11898 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [36] 11899 0
Box Hill Hospital - Box Hill
Recruitment hospital [37] 11900 0
Maroondah Hospital - Ringwood East
Recruitment hospital [38] 11901 0
Prince of Wales Hospital - Randwick
Recruitment hospital [39] 11902 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [40] 11903 0
The Canberra Hospital - Garran
Recruitment hospital [41] 11904 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [42] 11905 0
King Edward Memorial Hospital - Subiaco
Recruitment hospital [43] 11906 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [44] 11907 0
Mackay Base Hospital - Mackay
Recruitment hospital [45] 11908 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 8880 0
6000 - Perth
Recruitment postcode(s) [2] 24003 0
3050 - Parkville
Recruitment postcode(s) [3] 24004 0
3004 - Prahran
Recruitment postcode(s) [4] 24005 0
3175 - Dandenong
Recruitment postcode(s) [5] 24006 0
6008 - Subiaco
Recruitment postcode(s) [6] 24007 0
2305 - New Lambton
Recruitment postcode(s) [7] 24008 0
3220 - Geelong
Recruitment postcode(s) [8] 24009 0
3144 - Malvern
Recruitment postcode(s) [9] 24010 0
3168 - Clayton
Recruitment postcode(s) [10] 24011 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 24012 0
2148 - Blacktown
Recruitment postcode(s) [12] 24013 0
2145 - Westmead
Recruitment postcode(s) [13] 24014 0
3121 - Richmond
Recruitment postcode(s) [14] 24015 0
5000 - Adelaide
Recruitment postcode(s) [15] 24016 0
3000 - Melbourne
Recruitment postcode(s) [16] 24017 0
3011 - Footscray
Recruitment postcode(s) [17] 24018 0
4215 - Southport
Recruitment postcode(s) [18] 24019 0
2139 - Concord
Recruitment postcode(s) [19] 24020 0
6150 - Murdoch
Recruitment postcode(s) [20] 24021 0
2050 - Camperdown
Recruitment postcode(s) [21] 24022 0
3084 - Heidelberg
Recruitment postcode(s) [22] 24023 0
3076 - Epping
Recruitment postcode(s) [23] 24024 0
3350 - Ballarat Central
Recruitment postcode(s) [24] 24025 0
4029 - Herston
Recruitment postcode(s) [25] 24026 0
3065 - Fitzroy
Recruitment postcode(s) [26] 24027 0
7000 - Hobart
Recruitment postcode(s) [27] 24028 0
2500 - Wollongong
Recruitment postcode(s) [28] 24029 0
2109 - Macquarie Park
Recruitment postcode(s) [29] 24030 0
6168 - Cooloongup
Recruitment postcode(s) [30] 24031 0
2650 - Wagga Wagga
Recruitment postcode(s) [31] 24032 0
2194 - Campsie
Recruitment postcode(s) [32] 24033 0
2065 - St Leonards
Recruitment postcode(s) [33] 24034 0
4575 - Birtinya
Recruitment postcode(s) [34] 24035 0
6009 - Nedlands
Recruitment postcode(s) [35] 24036 0
3128 - Box Hill
Recruitment postcode(s) [36] 24037 0
3135 - Ringwood East
Recruitment postcode(s) [37] 24038 0
2031 - Randwick
Recruitment postcode(s) [38] 24039 0
2485 - Tweed Heads
Recruitment postcode(s) [39] 24040 0
2605 - Garran
Recruitment postcode(s) [40] 24041 0
5042 - Bedford Park
Recruitment postcode(s) [41] 24042 0
4020 - Redcliffe
Recruitment postcode(s) [42] 24043 0
4740 - Mackay
Recruitment postcode(s) [43] 24044 0
0810 - Tiwi
Recruitment outside Australia
Country [1] 20844 0
Hong Kong
State/province [1] 20844 0
Hong Kong
Country [2] 20845 0
South Africa
State/province [2] 20845 0
Cape Town
Country [3] 20846 0
Netherlands
State/province [3] 20846 0
Utrecht
Country [4] 20847 0
New Zealand
State/province [4] 20847 0
North Island and South Island

Funding & Sponsors
Funding source category [1] 290210 0
Government body
Name [1] 290210 0
National Health and Medical Research Council
Address [1] 290210 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 290210 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Alfred Health, Melbourne
Address
55 Commercial Rd, Prahran VIC 3181
Country
Australia
Secondary sponsor category [1] 288917 0
None
Name [1] 288917 0
Address [1] 288917 0
Country [1] 288917 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291917 0
Alfred Hospital
Ethics committee address [1] 291917 0
OFFICE OF ETHICS & RESEARCH GOVERNANCE - Ground Floor, Linay Pavilion, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004
Ethics committee country [1] 291917 0
Australia
Date submitted for ethics approval [1] 291917 0
16/07/2015
Approval date [1] 291917 0
03/09/2015
Ethics approval number [1] 291917 0

Summary
Brief summary
The PADDI Trial is a large (8,880 patients) international, multicentre, prospective, randomised, double blind, placebo-controlled, parallel assessment, stratified, non-inferiority safety and effectiveness study. It’s purpose is to establish the safety of the administration of 8mg of dexamethasone to adult patients undergoing non-urgent surgical procedures under general anaesthesia of at least two hours duration and requiring at least one night’s stay in hospital postoperatively. Patients will be stratified according to whether or not they are known to have diabetes. The primary outcome is the incidence of surgical site infection at 30 days postoperatively. Secondary outcomes include infection at other sites, and the incidence of chronic post-surgical pain at one year postoperatively. The influence of diabetic status and the quality of control of diabetes on all outcomes will be specifically explored.
Trial website
https://www.paddi.org.au/
Trial related presentations / publications
Recruitment updates at ANZCA CTN Research Workshop 2016, 2017, 2018
Public notes

Contacts
Principal investigator
Name 52582 0
Prof Tomas Corcoran
Address 52582 0
Department of Anaesthesia and Pain Medicine
Level 4, North Block
Royal Perth Hospital
Wellington Street
Perth
Western Australia
6000
Country 52582 0
Australia
Phone 52582 0
+61892241038
Fax 52582 0
Email 52582 0
mascor@bigpond.net.au
Contact person for public queries
Name 52583 0
Ms Jaspreet Sidhu
Address 52583 0
ANZCA Clinical Trials Network
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University
The Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 52583 0
Australia
Phone 52583 0
+61 438931818
Fax 52583 0
Email 52583 0
jaspreet.sidhu@monash.edu
Contact person for scientific queries
Name 52584 0
Prof Tomas Corcoran
Address 52584 0
Department of Anaesthesia and Pain Medicine
Level 4, North Block
Royal Perth Hospital
Wellington Street
Perth
Western Australia
6000
Country 52584 0
Australia
Phone 52584 0
+61892241038
Fax 52584 0
Email 52584 0
mascor@bigpond.net.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We receive de-identified patient data therefore cannot make this available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results