Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000364471
Ethics application status
Approved
Date submitted
15/03/2016
Date registered
21/03/2016
Date last updated
23/05/2022
Date data sharing statement initially provided
21/12/2018
Date results information initially provided
6/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
PICASSO: Prophylactic IncCsional Antibiotics in Skin Surgery trial. Can infiltrating antibiotics reduce the rate of wound infection?
Scientific title
Efficacy of incisional antibiotics to reduce wound infection and graft failure following excision of skin lesions
Secondary ID [1] 288769 0
none
Universal Trial Number (UTN)
U1111-1171-0431
Trial acronym
PICASSO
Prophylactic InCisional Antibiotics in Skin cancer Surgery
Linked study record

Health condition
Health condition(s) or problem(s) studied:
wound infection 298030 0
graft failure 298031 0
Condition category
Condition code
Surgery 298184 298184 0 0
Surgical techniques
Cancer 298197 298197 0 0
Non melanoma skin cancer
Cancer 298198 298198 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention

Arm 1: 1% LIDOCAINE plus ADRENALINE 1:100,000 buffered 1:10 with 8.4% sodium bicarbonate (50 mEq/50mL) plus FLUCLOXACILLIN 500 micrograms/mL delivered by injection into subcutaneous tissue as a field block immediately prior to skin excision as a single dose. The volume injected will vary between skin lesions according to amount deemed necessary by the operating surgeon.

Arm 2: 1% LIDOCAINE plus ADRENALINE 1:100,000 buffered 1:10 with 8.4% sodium bicarbonate (50 mEq/50mL) plus CLINDAMYCIN 408 micrograms/mL delivered by injection into subcutaneous tissue as a field block immediately prior to skin excision as a single dose. The volume injected will vary between skin lesions according to amount deemed necessary by the operating surgeon.
Intervention code [1] 294210 0
Prevention
Intervention code [2] 294221 0
Treatment: Drugs
Comparator / control treatment
Control

1% LIDOCAINE plus ADRENALINE 1:100,000 buffered 1:10 with 8.4% sodium bicarbonate (50 mEq/50mL) delivered by injection into subcutaneous tissue as a field block immediately prior to skin excision as a single dose. The volume injected will vary between skin lesions according to amount deemed necessary by the operating surgeon.
Control group
Placebo

Outcomes
Primary outcome [1] 297689 0
Wound infection: all surgical sites will be assessed at 5-10 days and 3-4 week time points postoperatively and graded for signs of infection as per the standardized scoring system adopted from Griego et al.
Griego R, Zitelli J. Intra-incisional prophylactic antibiotics for dermatologic surgery. Archives of Dermatology. 1998;134(6):688-92.
Timepoint [1] 297689 0
Once at 5 days post surgery and once at 3 weeks post surgery.
Secondary outcome [1] 321846 0
Graft take: all surgical sites closed with a skin graft will be assessed at 5-10 days and 3-4 week time points postoperatively and graded for percentage graft take. A transparent plastic film with a printed grid 1cm x 1cm will be used to estimate the total size of the graft and the percentage of graft take. Photographs will be taken for re-assessment by another observer.
Timepoint [1] 321846 0
Once at 5 days post surgery and once at 3 weeks post surgery.

Eligibility
Key inclusion criteria
All patients waitlisted for surgical management of skin lesions following specialist evaluation at the CMDHB Skin Cancer Centre and whom are able to provide consent independently.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of allergy to FLUCLOXACILLIN or CLINDAMYCIN.
Pre-operative administration of antibiotics.
Inability to return for follow up.
Inability to consent independently.

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)
Patients will be treated with de-identified injectable solutions with a unique code. The allocation to a particular group will only be known in hindsight to the study overseer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization of patient de-identified injectable will be assigned using random block sizes, stratified according to location of the surgical site (any site on a lower extremity vs. no site on a lower extremity), and will be delivered via opaque envelopes prepared by study statistician preoperatively.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
To account for the testing of two primary hypotheses, we apply a False Discovery Rate correction (equivalent in this case to a Bonferroni correction) to the nominal 5% significance level against two-sided hypotheses under which statistical inference will be effected in the intended full study. We further posit two reasonable values for expected infection rates under the hypothesis of a beneficial treatment effect, namely reductions from a 7% POWI rate to 3.5% and 2% respectively. We determine the expected study sizes required to achieve 80% power under these two scenarios: 2340 and 987 respectively.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/02/2019
Actual
18/02/2019
Date of last participant enrolment
Anticipated
31/07/2019
Actual
4/12/2019
Date of last data collection
Anticipated
1/12/2020
Actual
1/12/2020
Sample size
Target
2340
Accrual to date
Final
2340
Recruitment outside Australia
Country [1] 7708 0
New Zealand
State/province [1] 7708 0

Funding & Sponsors
Funding source category [1] 293135 0
Hospital
Name [1] 293135 0
New Zealand Health Research Council
Country [1] 293135 0
New Zealand
Primary sponsor type
Individual
Name
A/Prof (Hon) Jon Mathy
Address
Plastic, Reconstruction & Hand Department
Middlemore Hospital
100 Hospital Road
Auckland
2025
Country
New Zealand
Secondary sponsor category [1] 291930 0
None
Name [1] 291930 0
Address [1] 291930 0
Country [1] 291930 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294632 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 294632 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington
New Zealand
6011
Ethics committee country [1] 294632 0
New Zealand
Date submitted for ethics approval [1] 294632 0
30/11/2015
Approval date [1] 294632 0
14/03/2016
Ethics approval number [1] 294632 0
15/CEN/260

Summary
Brief summary
Delayed healing and graft failure secondary to infection contribute to morbidity amongst patients undergoing excision of melanoma and non-melanoma skin cancers. Infection delays healing and leads to more prominent scar formation while graft failure also delays healing and may necessitate further surgery or lead to chronic wounds. Such complications have a flow on effect economically as further nursing resources are occupied, dressings are required for longer and in younger patients a return to work may be delayed. The adjusted infection rate amongst patients undergoing excision of skin lesions through the Plastic, Reconstructing & Hands department at Middlemore Hospital is approximately 7%.
Studies have previously demonstrated that pre-operative infiltration of antibiotic to the incision site simultaneously with local anaesthetic leads to a reduction in post-operative wound infections1, 2. However, these studies have been performed in private Mohs micrographic surgery centres and the process has yet to be applied in a public setting. To our knowledge, the process has not been tested in patients requiring split thickness and full thickness skin grafts following excision of melanoma and non-melanoma skin cancers.
The approaching calamity of antibiotic resistance adds further impetus to the judicious use of antibiotics. Many surgeons routinely prescribe pre-operative antibiotics and/or a course of antibiotics post-operatively in an attempt to reduce morbidity. Not only does this systemic approach contribute to the evolution of antibiotic resistance but it certainly confers morbidity in terms of antibiotic side effects to some patients. Here we seek to apply the principle of intra-incisional antibiotics in a high volume public care setting to determine whether this more judicious use of antibiotics can reduce post-operative wound infection and graft failure secondary to infection.
Trial website
nil
Trial related presentations / publications
nil
Public notes
nil

Contacts
Principal investigator
Name 64414 0
Mr Jon Mathy
Address 64414 0
Department of Plastic, Reconstructive and Hand Surgery
100 Hospital Road
Middlemore Hospital
Auckland
2025
Country 64414 0
New Zealand
Phone 64414 0
+64 9 276 0000
Fax 64414 0
Email 64414 0
[email protected]
Contact person for public queries
Name 64415 0
Mr Jon Mathy
Address 64415 0
Department of Plastic, Reconstructive and Hand Surgery
100 Hospital Road
Middlemore Hospital
Auckland
2025
Country 64415 0
New Zealand
Phone 64415 0
+64 9 276 0000
Fax 64415 0
Email 64415 0
[email protected]
Contact person for scientific queries
Name 64416 0
Mr Jon Mathy
Address 64416 0
Department of Plastic, Reconstructive and Hand Surgery
100 Hospital Road
Middlemore Hospital
Auckland
2025
Country 64416 0
New Zealand
Phone 64416 0
+64 9 276 0000
Fax 64416 0
Email 64416 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
individual data will not be released to respect patient confidentiality


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.