ANZCTR - Registration

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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

28/07/2020

Date data sharing statement initially provided

4/06/2019

Date results provided

28/07/2020

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]

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

Perioperative Infective Complications

Surgery

Condition category

Condition code

Anaesthesiology

Anaesthetics

Metabolic and Endocrine

Diabetes

Infection

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]

Treatment: Drugs

Intervention code [2]

Prevention

Comparator / control treatment

Placebo (intravenous saline)

Control group

Placebo

Outcomes

Primary outcome [1]

Surgical Site Infection- CDC definitions

Timepoint [1]

30 days postoperatively

Secondary outcome [1]

1.Deep and organ space infections to 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 [1]

90 days postoperatively

Secondary outcome [2]

2. Superficial, deep and organ space infections to 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 [2]

30 days postoperatively

Secondary outcome [3]

3. Other infections up to 30 days after the index procedure (i.e.urinary tract infections, pneumonia, catheter-related infections and sepsis), considered separately and together . (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]

30 days postoperatively

Secondary outcome [4]

4. Quality of recovery: QoR-15 score on days 1 and 30

Timepoint [4]

Post-op Day 1 and Day 30

Secondary outcome [5]

5. Chronic Post-Surgical Pain (CPSP) at 6 months after surgery using the following metrics:
(a) The presence of CPSP, defined as pain reported by the patient at the 6 months follow-up, in the area of the index surgery which was not present prior to surgery
(b) The presence of Pain at 6 months in the area of the index surgery, regardless of presence prior to surgery
(c) Severity of CPSP (using the adapted mBPI-sf).
(d) Incidence and severity of neuropathic symptoms and pain (incidence examined as a binary outcome using the Neuropathic Pain Questionnaire, severity quantified using the adapted mBPI-sf).
Patient reported outcome based on validated questionnaires - Neuropathic Pain Questionnaire and the mBPI Modified Brief Pain Inventory..

Timepoint [5]

6 Months postoperatively

Secondary outcome [6]

6. Death or persistent new onset disability for 6 months following surgery. Persistent new onset disability is defined as a 4-point (8%) or greater increase in the 12-item WHODAS 2.0 score compared with baseline (preoperative) score at both 30 days and 6 months.

Timepoint [6]

Day 30 and 6 month postoperatively

Secondary outcome [7]

T1. Any nausea or vomiting postoperatively to 24 hours post-surgery. This is based on the numerical rating scale of nausea as asked of the patient and documented evidence of vomiting events.
The patient will be asked at Day 1 review and if they are unable to answer, Medical record charts will be reviewed such as observation charts, medication charts, pain infusion charts and daily medical notes by a member of the research team

Timepoint [7]

24 hours postoperatively

Secondary outcome [8]

T2. Any antiemetic usage postoperatively to 24 hours post-surgery. This is based on documented evidence of antiemetic usage in the patient's medical records in accordance with the study visit schedule.

Timepoint [8]

24 hours postoperatively

Secondary outcome [9]

T3. Nausea (Up to Day 3) –
(a) 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, on day 3.
(b) Antiemetic usage in each of these periods.

a) The patient's medical record charts will be reviewed such as PACU chart, observation charts, medication charts, pain infusion charts and daily medical notes by a member of the research team
b) The patient's medication chart will be reviewed for the use of any antiemetics in these time frames

Timepoint [9]

Post op Day 1, 2 and 3

Secondary outcome [10]

T4. Vomiting (Up to Day 3) –
Number of vomiting events in PACU, within first 24 hours following surgery post PACU, on day 2 and on day 3.
The patient's medical record charts will be reviewed such as PACU chart, observation charts, medication charts, pain infusion charts and daily medical notes by a member of the research team

Timepoint [10]

Post op Day 1, 2 and 3

Secondary outcome [11]

T5. Highest pain score (NRS, 0–10) at rest and on movement in PACU and in the first 24 hours post-PACU

Timepoint [11]

24 hours post PACU

Secondary outcome [12]

T6. Hospital stay: from the start (date, time) of surgery until discharge from acute care facility.

The patient's electronic medical record will be reviewed by a member of the research team

Timepoint [12]

Up to 6 months postoperative

Secondary outcome [13]

T7. CRP concentration – measured on Day 2 postoperatively through serum assay.

Timepoint [13]

Day 2 postoperative

Secondary outcome [14]

T8. Glycaemic control, defined as the maximal changes in perioperative blood glucose from baseline up to day 2 postoperatively,

Duration of Hospital stay: from the start (date, time) of surgery until 48 hours post op, where blood glucose monitoring has been undertaken during this time frame. The patient's medical record charts will be reviewed such as PACU chart, observation charts and daily medical notes by a member of the research team

Timepoint [14]

postoperative up to Day 2

Secondary outcome [15]

T9. Hypoglycaemic event rates - a hypoglycaemic event being defined as a blood glucose recording less than 4.0 mmol/L.

Timepoint [15]

Postoperative up to Day of Discharge

Secondary outcome [16]

T10. Hyperglycaemic event rates in patients without diabetes - a hyperglycaemic event being defined as a blood glucose recording greater than 10 mmol/L.

Timepoint [16]

Postoperative up to Day of Discharge

Secondary outcome [17]

T11. Rate of insulin use in patients without diabetes. This is based on data collected of insulin use outside of 'usual' treatment.
The patient's medical record charts will be reviewed such as PACU chart, Medication charts, insulin infusion charts and daily medical notes by a member of the research team

Timepoint [17]

Postoperative up to Day of Discharge

Secondary outcome [18]

T12. Lymphocyte and neutrophil levels - Change in neutrophil-to-lymphocyte ratios from baseline to Days 1 and 2. This outcome is based on the patient's pathology results.

Timepoint [18]

Postoperative to day 1 and day 2

Secondary outcome [19]

T13. Mortality at 6 months

Timepoint [19]

Postoperative up to 6 months

Secondary outcome [20]

T14. Unexpected reoperation to 30 days

Duration of Hospital stay: from the start (date, time) of surgery until 30 days post op. This will be reviewed from patients electronic medical records

Timepoint [20]

Postoperative up to 30 days

Secondary outcome [21]

T15. Unexpected readmission to hospital to 30 days

Duration of Hospital stay: from the start (date, time) of surgery until 30 days post op. This will be reviewed from patients electronic medical records

Timepoint [21]

Postoperative up to 30 days

Eligibility

Key inclusion criteria

Adult patients 18 years or older
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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

16/12/2015

Actual

10/03/2016

Date of last participant enrolment

Anticipated

6/06/2019

Actual

29/07/2019

Date of last data collection

Anticipated

31/12/2019

Actual

23/02/2020

Sample size

Target

8880

Accrual to date

Final

8880

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

Royal Perth Hospital - Perth

Recruitment hospital [2]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [3]

The Alfred - Prahran

Recruitment hospital [4]

Dandenong Hospital - Dandenong

Recruitment hospital [5]

St John of God Hospital, Subiaco - Subiaco

Recruitment hospital [6]

John Hunter Hospital Royal Newcastle Centre - New Lambton

Recruitment hospital [7]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [8]

Cabrini Hospital - Malvern - Malvern

Recruitment hospital [9]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [10]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [11]

Blacktown Hospital - Blacktown

Recruitment hospital [12]

Westmead Hospital - Westmead

Recruitment hospital [13]

Epworth Richmond - Richmond

Recruitment hospital [14]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [15]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [16]

Western Hospital - Footscray - Footscray

Recruitment hospital [17]

Gold Coast University Hospital - Southport

Recruitment hospital [18]

Concord Repatriation Hospital - Concord

Recruitment hospital [19]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [20]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [21]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [22]

The Northern Hospital - Epping

Recruitment hospital [23]

Ballarat Health Services (Base Hospital) - Ballarat Central

Recruitment hospital [24]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [25]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment hospital [26]

Royal Hobart Hospital - Hobart

Recruitment hospital [27]

Wollongong Hospital - Wollongong

Recruitment hospital [28]

St John of God Hospital, Ballarat - Ballarat

Recruitment hospital [29]

Macquarie University Hospital - Macquarie Park

Recruitment hospital [30]

Rockingham General Hospital - Cooloongup

Recruitment hospital [31]

Wagga Wagga Base Hospital - Wagga Wagga

Recruitment hospital [32]

Canterbury Hospital - Campsie

Recruitment hospital [33]

Royal North Shore Hospital - St Leonards

Recruitment hospital [34]

Sunshine Coast University Hospital - Birtinya

Recruitment hospital [35]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [36]

Box Hill Hospital - Box Hill

Recruitment hospital [37]

Maroondah Hospital - Ringwood East

Recruitment hospital [38]

Prince of Wales Hospital - Randwick

Recruitment hospital [39]

The Tweed Hospital - Tweed Heads

Recruitment hospital [40]

The Canberra Hospital - Garran

Recruitment hospital [41]

Flinders Medical Centre - Bedford Park

Recruitment hospital [42]

King Edward Memorial Hospital - Subiaco

Recruitment hospital [43]

Redcliffe Hospital - Redcliffe

Recruitment hospital [44]

Mackay Base Hospital - Mackay

Recruitment hospital [45]

Royal Darwin Hospital - Tiwi

Recruitment hospital [46]

Gosford Hospital - Gosford

Recruitment postcode(s) [1]

6000 - Perth

Recruitment postcode(s) [2]

3050 - Parkville

Recruitment postcode(s) [3]

3004 - Prahran

Recruitment postcode(s) [4]

3175 - Dandenong

Recruitment postcode(s) [5]

6008 - Subiaco

Recruitment postcode(s) [6]

2305 - New Lambton

Recruitment postcode(s) [7]

3220 - Geelong

Recruitment postcode(s) [8]

3144 - Malvern

Recruitment postcode(s) [9]

3168 - Clayton

Recruitment postcode(s) [10]

4102 - Woolloongabba

Recruitment postcode(s) [11]

2148 - Blacktown

Recruitment postcode(s) [12]

2145 - Westmead

Recruitment postcode(s) [13]

3121 - Richmond

Recruitment postcode(s) [14]

5000 - Adelaide

Recruitment postcode(s) [15]

3000 - Melbourne

Recruitment postcode(s) [16]

3011 - Footscray

Recruitment postcode(s) [17]

4215 - Southport

Recruitment postcode(s) [18]

2139 - Concord

Recruitment postcode(s) [19]

6150 - Murdoch

Recruitment postcode(s) [20]

2050 - Camperdown

Recruitment postcode(s) [21]

3084 - Heidelberg

Recruitment postcode(s) [22]

3076 - Epping

Recruitment postcode(s) [23]

3350 - Ballarat Central

Recruitment postcode(s) [24]

4029 - Herston

Recruitment postcode(s) [25]

3065 - Fitzroy

Recruitment postcode(s) [26]

7000 - Hobart

Recruitment postcode(s) [27]

2500 - Wollongong

Recruitment postcode(s) [28]

3350 - Ballarat

Recruitment postcode(s) [29]

2109 - Macquarie University

Recruitment postcode(s) [30]

6168 - Rockingham

Recruitment postcode(s) [31]

2650 - Wagga Wagga South

Recruitment postcode(s) [32]

2193 - Canterbury

Recruitment postcode(s) [33]

2065 - Crows Nest

Recruitment postcode(s) [34]

4575 - Wurtulla

Recruitment postcode(s) [35]

6009 - Broadway Nedlands

Recruitment postcode(s) [36]

3128 - Box Hill Central

Recruitment postcode(s) [37]

3135 - Heathmont

Recruitment postcode(s) [38]

2031 - Clovelly West

Recruitment postcode(s) [39]

2485 - Tweed Heads West

Recruitment postcode(s) [40]

2605 - Curtin

Recruitment postcode(s) [41]

5042 - Flinders University

Recruitment postcode(s) [42]

6008 - Subiaco East

Recruitment postcode(s) [43]

4020 - Redcliffe North

Recruitment postcode(s) [44]

4740 - Mackay West

Recruitment postcode(s) [45]

0810 - Muirhead

Recruitment postcode(s) [46]

2250 - Gosford

Recruitment outside Australia

Country [1]

Hong Kong

State/province [1]

Hong Kong

Country [2]

South Africa

State/province [2]

Cape Town

Country [3]

New Zealand

State/province [3]

North Island and South Island

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Alfred Health, Melbourne

Address

55 Commercial Rd, Prahran VIC 3181

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital

Ethics committee address [1]

OFFICE OF ETHICS & RESEARCH GOVERNANCE - Ground Floor, Linay Pavilion, The Alfred Hospital,  55 Commercial Road, Melbourne, Victoria 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/07/2015

Approval date [1]

03/09/2015

Ethics approval number [1]

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, 2019

Public notes

Contacts

Principal investigator

Name

Prof Tomas Corcoran

Address

Department of Anaesthesia and Pain Medicine
Level 4, North Block
Royal Perth Hospital
Wellington Street
Perth
Western Australia
6000

Country

Australia

Phone

+61892241038

Fax

[email protected]

Contact person for public queries

Name

Pauline Coutts

Address

ANZCA Clinical Trials Network
Central Clinical School
Monash University
The Alfred Centre
99 Commercial Road
Melbourne VIC 3004

Country

Australia

Phone

+61 438931818

Fax

[email protected]

Contact person for scientific queries

Name

Tomas Corcoran

Address

Department of Anaesthesia and Pain Medicine
Level 4, North Block
Royal Perth Hospital
Wellington Street
Perth
Western Australia
6000

Country

Australia

Phone

+61892241038

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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 Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Dexamethasone and Surgical-Site Infection; May 6... [More Details]	367381-(Uploaded-02-06-2021-14-54-33)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The perioperative administration of dexamethasone and infection (PADDI) trial protocol: Rationale and design of a pragmatic multicentre non-inferiority study.	2019	https://dx.doi.org/10.1136/bmjopen-2019-030402
Embase	Dexamethasone and surgical-site infection.	2021	https://dx.doi.org/10.1056/NEJMoa2028982
Embase	Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.	2022	https://dx.doi.org/10.1016/j.bja.2022.05.018
Embase	Dexamethasone and persistent wound pain: a prespecified analysis of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial.	2023	https://dx.doi.org/10.1016/j.bja.2023.03.031

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically