Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000123246
Ethics application status
Approved
Date submitted
24/11/2017
Date registered
29/01/2018
Date last updated
30/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Intravenous lidocaine in the prevention of postoperative ileus
Scientific title
A randomised double blind placebo controlled trial of intravenous lidocaine to reduce the duration of postoperative ileus in patients undergoing elective colorectal surgery
Secondary ID [1] 293359 0
none
Universal Trial Number (UTN)
U1111-1198-4332
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post operative ileus 305478 0
Condition category
Condition code
Surgery 304732 304732 0 0
Other surgery
Oral and Gastrointestinal 304733 304733 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in the intervention group undergoing colorectal surgery will be administered intravenous lidocaine. The dose of lidocaine will be 2mg/kg bolus at induction of anaesthesia with a 2mg/kg/hr infusion to a maximum of 150mg/hr, the infusion will continue until 2 hours post op
Intervention code [1] 299616 0
Prevention
Intervention code [2] 299617 0
Treatment: Drugs
Comparator / control treatment
Patients in the control group will receive a placebo in the form of normal saline 0.9% via intravenous administration
Control group
Placebo

Outcomes
Primary outcome [1] 303950 0
Duration of post operative ileus
- this is a composite outcome measured by time till tolerating solid food and time till passage of stool - assessed by nursing staff on ward as part of Enhanced Recovery After Surgery (ERAS) protocol, or by self reporting by participants if discharged from hospital prior to achieving these outcomes
Timepoint [1] 303950 0
Measurements will be taken twice daily until outcome is achieved.
Maximum follow-up will be 7 days post discharge from hospital
Secondary outcome [1] 340525 0
Post operative pain as measured by composite measures of visual analogue scale and morphine equivalent dose
Timepoint [1] 340525 0
Measured twice daily until date of discharge
Secondary outcome [2] 340527 0
Time until discharge from hospital
Timepoint [2] 340527 0
Will be assessed twice daily until time of discharge
Secondary outcome [3] 341430 0
Complication rates
For example
Operative complications - wound infection, anastomotic leak, post operative haemorrhage, As diagnosed by the treating team
Other non-operative complications - Cardiovascular complications (myocardial infarct, arrhythmia), respiratory complications (pneumonia), neurological complications (seizure) will be diagnosed by the treating team,
Timepoint [3] 341430 0
All post operative complications will be recorded until 30 days post operatively
Secondary outcome [4] 341431 0
Systemic inflammation marker levels - CRP and WCC
Timepoint [4] 341431 0
These blood markers of inflammation will be recorded as per usual care until the time of discharge. Usual care would be for daily blood testing until the date of discharge

Eligibility
Key inclusion criteria
All patients undergoing elective colorectal surgery
Able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Allergy to lidocaine
• ASA 4 or greater
• Active inflammatory bowel disease
• Moderate to severe renal impairment (Creatinine clearance <50ml/min/1.73m2)
• Severe hepatic impairment (Child-Pugh C)
• Moderate to severe congestive cardiac failure (NHYA 3 or 4)
• Pregnancy
• Pre-existing gut dysmotility disorder including endocrine, metabolic or neurological cause
• Pre-operative malnutrition requiring parenteral nutrition
• Inability to give consent or participate in post-operative assessments
• Primary, secondary or tertiary heart block
• Shock
• Drugs known to reduce lidocaine metabolism e.g. cimetidine

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)
Yes - central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted 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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Previously unpublished data obtained as part of a prospective trial on post-operative ileus at Auckland City Hospital, was provided to us by colleagues at Auckland City Hospital. Data was extracted from 93 patients undergoing elective bowel resection without ileostomy formation, forming the basis of our power calculations. Retrospective data showed mean time to both tolerance of a solid diet and passage of stool = 4.9 days (SD = 2.6 days). This calculation has been performed with the assistance of a statistician. Assumptions were a= 0.05, ß= 0.2, Power= 80% and for a two-tailed test. Allocation ratio was 1:1. The study is designed to find a difference between 2 independent means.
To detect a clinically relevant reduction of 36 hours (25%) in the time to tolerate food and pass stool (from 4.9 days to 3.6 days) n= 64 patients required per group, therefore a total of 128 patients will need to be recruited for this study. We will aim to recruit 140 patients in order to account for any dropout.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2018
Actual
Date of last participant enrolment
Anticipated
28/09/2018
Actual
Date of last data collection
Anticipated
5/10/2018
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment outside Australia
Country [1] 9357 0
New Zealand
State/province [1] 9357 0
Canterbury

Funding & Sponsors
Funding source category [1] 298065 0
Hospital
Name [1] 298065 0
Departments of Surgery and Anaesthesia, Christchurch Hospital
Country [1] 298065 0
New Zealand
Primary sponsor type
University
Name
University of Otago, Christchurch
Address
2 Riccarton Ave
Christchurch 8011
Country
New Zealand
Secondary sponsor category [1] 297141 0
Hospital
Name [1] 297141 0
Christchurch Hospital
Address [1] 297141 0
2 Riccarton Ave
Christchurch 8011
Country [1] 297141 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299022 0
Health and Disability Ethics Committees
Ethics committee address [1] 299022 0
Ministry of Health
133 Molesworth St
PO Box 5013
Wellington
6011
Ethics committee country [1] 299022 0
New Zealand
Date submitted for ethics approval [1] 299022 0
16/08/2017
Approval date [1] 299022 0
09/11/2017
Ethics approval number [1] 299022 0
17/NTA/180

Summary
Brief summary
Postoperative ileus (POI) is a common sequelae of abdominal surgery and is characterised by a period of gastrointestinal dysmotility. Common symptoms include nausea, vomiting, inability to tolerate oral diet and inability to pass flatus or stool. Patients with POI commonly have abdominal distension, they may require nasogastric tube (NGT) insertion to relieve gastric distension. POI interferes with patient mobility post operatively and evidence suggests that more than 50% of patients who develop POI will also develop further complications, significantly increasing their postoperative length of stay and mortality.
POI is a common condition, a recent series at Auckland City Hospital identified 26.9% of patients as having prolonged postoperative ileus. This is an issue which places a significant burden on healthcare resources and spending; a recent study estimates an annual economic burden of over $1.4 billion in the United States alone.
The exact mechanism of POI is unclear, however important factors in its development include use of pharmacological agents (particularly opiates), neural mechanisms, and intestinal inflammation. Anti-inflammatory drugs such as COX-2 inhibitors have shown some effect in animal and human models in preventing and reducing the duration of POI.
Lidocaine is a local anaesthetic medication. Similar local anaesthetic medications are routinely used in elective surgery for analgesia via epidural or local infiltration. There is evidence that epidural local anaesthetic is effective in the prevention of POI. It has recently been suggested that the clinical effect is due to systemic absorption of the local anaesthetic, studies have shown that intravenously administered local anaesthetic is effective at reducing rates of POI. The mechanism of action may be due to reduced opiate consumption post operatively due to the analgesic effect of lidocaine, however studies have shown a significant attenuation of the post-surgical inflammatory response following administration of parenteral lidocaine, and this may also contribute to its’ effect.
This study aims to assess the duration of POI following the administration of parenteral lidocaine intraoperatively and up to 2 hours post operatively, compared to placebo. Primary end points will include, time to resolution of POI as defined by established criteria. Secondary end points will include pain scores, markers of systemic inflammation, complication rates and length of hospital stay.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79018 0
Dr Michael Russell
Address 79018 0
Dept of General Surgery
Christchurch Hospital
2 Riccarton Ave
Christchurch 8011
Country 79018 0
New Zealand
Phone 79018 0
+64221572420
Fax 79018 0
Email 79018 0
[email protected]
Contact person for public queries
Name 79019 0
Dr Michael Russell
Address 79019 0
Dept of General Surgery
Christchurch Hospital
2 Riccarton Ave
Christchurch 8011
Country 79019 0
New Zealand
Phone 79019 0
+64 3-364 0640
Fax 79019 0
Email 79019 0
[email protected]
Contact person for scientific queries
Name 79020 0
Dr Michael Russell
Address 79020 0
Dept of General Surgery
Christchurch Hospital
2 Riccarton Ave
Christchurch 8011
Country 79020 0
New Zealand
Phone 79020 0
+64 3-364 0640
Fax 79020 0
Email 79020 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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