Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000100190
Ethics application status
Approved
Date submitted
4/01/2019
Date registered
23/01/2019
Date last updated
22/11/2021
Date data sharing statement initially provided
23/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Lignocaine infusion on Donor Site Pain in Patients with Burns study
Scientific title
Prospective, randomised, controlled trial studying the analgesic effects of intravenous lignocaine on donor site pain in patients with burns.
Secondary ID [1] 296549 0
none
Universal Trial Number (UTN)
Trial acronym
LIDO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post operative pain 310332 0
Condition category
Condition code
Anaesthesiology 309063 309063 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At the time of surgery for first Split skin graft treatment for burn injury.
Group 1 will receive standard therapy (opioids and anti-neuropathic agents) with addition of intravenous Lignocaine bolus (1.5mg/kg) and intravenous Lignocaine infusion (1.25mg/kg/hr) started pre-incision and continued for 24hrs,
Group 2 will receive standard therapy plus intravenous 0.9% saline bolus and intravenous 0.9% saline infusion continued for 24 hrs.
Standard therapy as follows unless medically contraindicated:
Paracetamol 1gram Four times a day
Celecoxib 100mg twice a day
Opioids Slow release(MS Contin/Oxycontin/Targin) Given orally twice a day Titrated to effect
Opioids Immediate release (Endone/Ordine) Given orally as required titrated to effect
Pregabalin Given orally twice a day. Titrated from 50mg twice a day up to maximum 300mg twice a day Titrated to effect
Intervention code [1] 312858 0
Treatment: Drugs
Comparator / control treatment
Group 2 as above
Control group
Placebo

Outcomes
Primary outcome [1] 308035 0
Difference in Numerical rating Pain score at Donor site day 1 post SSG surgery, between groups
Timepoint [1] 308035 0
24 hours post initiation of Trial drug infusion
Secondary outcome [1] 353748 0
Highest pain score using numerical rating pain score (out of 10)
Timepoint [1] 353748 0
Highest pain scores recorded day 1-5 post SSG surgery
Secondary outcome [2] 353749 0
Neuropathic pain score using neuropathic pain scale (score out of 100)
Timepoint [2] 353749 0
Neuropathic pain score recorded days 1-5 post SSG surgery and 6 months post Burns injury
Secondary outcome [3] 353750 0
Oral Morphine equivalents OME (mg)
Assessed using the Faculty of pain medicine opioid calculator which allows comparison of opioid drugs and doses by calculating an OME dose in milligrams per day. Recorded as OME in milligrams
Timepoint [3] 353750 0
OME (mg) recorded days 1-5 post SSG surgery
Secondary outcome [4] 353751 0
Severity and incidence of persistent post-operative pain using Brief pain inventory
Timepoint [4] 353751 0
Brief Pain Inventory recorded 6 months post Burn Injury
Secondary outcome [5] 366076 0
Overall (average) pain score using a numerical rating scale from 0-10
Timepoint [5] 366076 0
Overall (average) pain scores recorded day 1-5 post SSG surgery

Eligibility
Key inclusion criteria
Greater than or equal to 7% TBSA (total burn surface area)
1st SSG (split skin graft) surgery
Age 18 years or older
Capacity to record pain scores and consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients already receiving Lignocaine infusion or oral mexilatine
Allergies to amide local anesthetics
Cardiac arrhythmia's such as 2nd/3rd degree heart block, Wolf Parkinson White
Heart failure
Hepatic failure
Hyperkalaemia
Patient refusal

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer (Pharmacy staff only)
All research team members, medical and nursing staff and patient are blinded to randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation with two stratification blocks:
>/< 20% Total Body Surface Area Burn
>40mg OME Chronic use (Chronic use defined as>7 consecutive days pre admission with burn injury)
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
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
A feasibility analysis has been completed with 57 eligible patients admitted over a 14 month period. Sample size has been calculated from this data: 104 patients (52 in each group) will provide 80% power (a 0.05) to demonstrate a reduction of pain scores by 30% with the addition of Lignocaine infusion to standard care.

The analysis of the primary endpoint, overall pain score specific to donor site pain (at rest) on Day 1, will be based on a mixed model analysis using the method of residual maximum likelihood (REML) with fixed effects for stratum, treatment group and their two-way interaction, and, random effects for patients. The predicted treatment group means from the REML analysis will be compared via the Wald Test (a=0.05) and standard errors of the means, and the standard error of their difference will also be reported. If the Wald Test for the two-way interaction is significant (p = 0.05), the outcomes of t-tests comparing the predicted treatment group means within each of the four strata will also be reported. In two separate supplementary analyses of the primary endpoint, covariates for the highest and overall pain scores in the 24 hours pre-op will be included in the mixed model and the Wald Tests for the covariate and the interaction of the covariate with treatment group will also be reported.
The repeated measurements of the donor site pain scores and also the repeated measurements of the pre and post op overall pain scores will be analysed using the REML method and the mixed model will include additional fixed effects for time and all interactions of time with the other fixed effects. The Akaike Information Criterion (AIC) will be used to select an appropriate autocorrelation model for the repeated measurements within individual patients. As the pain scores are bounded outcome scores, diagnostic plots of residuals will be examined and, if necessary, a variance-stabilising transformation of the scores, such as the empirical logit transformation, will be used when reporting tests of hypotheses. Further details will be documented in a Statistical Analysis Plan (SAP) prior to database lock and the unblinding of the Trial Management Committee.
Summary statistics will be used to describe the baseline demographic and clinical data and presented as mean ± SD, median with interquartile range (IQR) or percentages as appropriate. Chi squared analysis with Fisher’s exact test (when appropriate) and Student’s t test (Mann Whitney U test for non-normal distributions) will be used to compare baseline data between the lignocaine and placebo groups if required by external reviewers.with statistical significance declared for probability values of 0.05 or less. All analyses will be undertaken using thean intention-to-treat principle and patients in the Full Analysis Set (FAS) will be analysed according to the stratum to which they were assigned at randomization and the treatment group to which they were randomized.. In the event that one or more patients have their treatment allocations unblinded to the Research Nurses, an additional sensitivity analysis of the primary outcome will be conducted with data from these patients, and other patients with major protocol deviations (i.e. the Per-Protocol Set), excluded.Sensitivity analyses will be undertaken to account for any baseline imbalance.
The incidence and severity of neurological and cardiovascular adverse events in patients who receive at least one dose of the lignocaine or saline solution (the Safety Set) will be reported by preferred term and by “treatment actually received” - patients who receive at least one dose of lignocaine solution will be included in the lignocaine group, regardless of the group to which they were assigned at randomization. Further details of the adverse event summaries will be included in the SAP.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/01/2019
Actual
6/03/2019
Date of last participant enrolment
Anticipated
16/07/2022
Actual
Date of last data collection
Anticipated
25/11/2022
Actual
Sample size
Target
104
Accrual to date
14
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12374 0
The Alfred - Prahran
Recruitment postcode(s) [1] 24637 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 301129 0
Other Collaborative groups
Name [1] 301129 0
ANZCA Pilot Grant
Country [1] 301129 0
Australia
Primary sponsor type
Hospital
Name
The Alfred
Address
55 Commercial Road
Prahran
VIC 3004
Country
Australia
Secondary sponsor category [1] 300751 0
None
Name [1] 300751 0
Address [1] 300751 0
Country [1] 300751 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301880 0
Alfred Hospital Ethics Committee EC00315
Ethics committee address [1] 301880 0
The Alfred
55 Commercial Road
VIC 3004
Ethics committee country [1] 301880 0
Australia
Date submitted for ethics approval [1] 301880 0
28/06/2018
Approval date [1] 301880 0
10/09/2018
Ethics approval number [1] 301880 0
292/18

Summary
Brief summary
We propose a trial to assess if intravenous (into the bloodstream via a vein) Lignocaine infusion helps to reduce donor site pain in patients undergoing split skin grafting (SSG) following major burns.
The pain caused by a burns injury can be difficult to manage and often needs high doses of strong pain killing medications. Patients often report that the pain from the skin graft donor site can be as severe as the pain from the burn itself. The pain from the donor site is often poorly responsive to strong painkillers such as morphine. Lignocaine is commonly used for pain that is generated by damaged nerves (neuropathic pain). There is evidence to support use of Lignocaine to reduce the pain caused by other burns procedures such as dressing changes. There is currently no evidence regarding the use of Lignocaine for pain that is specific to the donor site. This study will help to guide evidence based practice regarding Lignocaine infusions for donor site pain.

We will randomly assign all patients admitted under the Burns team at The Alfred who are older than 18 years, who have a burn affecting over 10% of their body surface area and who have the capacity to record pain scores and consent, to one of two groups;
Group one will receive standard care plus a bolus and intravenous infusion of Lignocaine
Group two will receive standard care plus a bolus and intravenous infusion of Saline
(Saline has no effect on pain and acts as a placebo).

Neither the patients nor the medical teams will know which patients are in which group. We will record information about the pain the patient is experiencing and also the pain medications they are using before and after the surgery. The infusions will run for 24 hours. We will continue to follow up the patients for 5 days after their surgery. All the patients will be reviewed by the acute pain team who will assess the patient’s pain and make adjustments to the other pain treatments the patients receive. We have a strict protocol for how the medications can be increased. Treating pain is the first priority and no patient will have pain that is uncontrolled as a result of the trial.

We will collect two blood samples during the trial to assess the blood level of the trial drug Lignocaine. One will be taken whilst the patient is asleep during their surgery and the second will be taken when the infusion is stopped. The second sample will be taken with the usual post-operative blood tests to minimise extra blood tests.

We will follow up the patients 6 months following their burns injury to ask them if they have any ongoing pain that is caused by their burns injury. If they answer yes we will ask them a brief questionnaire asking them about their pain and also collect a list of the medications they are taking for pain.

All data collected as part of the trial will be de-identified at all stages and will be submitted for publication in a medical journal.
Results of the trial will be available if the patients request it through the burns team, although we will not be able to release any individual data.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88418 0
Dr Kerry Mclaughlin
Address 88418 0
Department of Anaesthesia and Perioperative Medicine
The Alfred
55 Commercial Road
Prahran
VIC 3004
Country 88418 0
Australia
Phone 88418 0
+61 390762000
Fax 88418 0
Email 88418 0
[email protected]
Contact person for public queries
Name 88419 0
Dr Kerry Mclaughlin
Address 88419 0
Department of Anaesthesia and Perioperative Medicine
The Alfred
55 Commercial Road
Prahran
VIC 3004
Country 88419 0
Australia
Phone 88419 0
+61 390762000
Fax 88419 0
Email 88419 0
[email protected]
Contact person for scientific queries
Name 88420 0
Dr Kerry Mclaughlin
Address 88420 0
Department of Anaesthesia and Perioperative Medicine
The Alfred
55 Commercial Road
Prahran
VIC 3004
Country 88420 0
Australia
Phone 88420 0
+61 390762000
Fax 88420 0
Email 88420 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
Data is deidentified


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
165Ethical approval    376340-(Uploaded-04-01-2019-08-52-24)-Study-related document.pdf
930Informed consent form    376340-(Uploaded-07-02-2020-09-15-23)-Study-related document.docx



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.