Condition category
Digestive System
Date applied
13/06/2018
Date assigned
13/06/2018
Last edited
14/06/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
A common problem in about 40% of patients having colorectal (large bowel) surgery is that their gut takes longer than normal to start working again. In most patients the gut will start working after surgery in 2-3 days, but in some it takes a week or more. This delayed recovery causes nausea, vomiting, complete constipation, tummy pain and tummy swelling and can take days to improve. During this time patients have to stay in hospital with a continuous intravenous drip and often need insertion of a nasogastric tube to empty the stomach to reduce vomiting (most patients find this very unpleasant).
Lidocaine (a local anaesthetic) used intravenously (through the vein) has been shown to reduce pain and inflammation after surgery and seems to help other aspects of recovery that may be important for return of gut function, for example reducing nausea and vomiting.
The ALLEGRO study hopes to find out if lidocaine can help improve the recovery of gut function in patients after bowel surgery. Half of the people who agree to take part in ALLEGRO will receive the intravenous lidocaine and half will receive a placebo (or dummy) salt solution intravenously. We will then compare the two groups and see whether gut function returns more quickly in the group who have received intravenous lidocaine

Who can participate?
Adults having certain types of surgery to their colon or rectum (large bowel).

What does the study involve?
Participants will be randomly allocated to receive intravenous lidocaine or placebo salt solution continuously for 6-12 hours starting at the start of general anaesthesia. They will undergo the planned surgery and aftercare as normal.

What are the possible benefits and risks of participating?
We hope that intravenous lidocaine may help to prevent gut problems after surgery, leading to faster recovery and discharge from hospital. However, there may be no medical benefit to you from participation in this study. This study will help to determine whether intravenous lidocaine can help gut recovery in patients having bowel surgery. The information we get from this study may help us to improve treatment of future patients requiring bowel surgery.
It is not thought that there are any disadvantages of taking part in this research study. You are undergoing scheduled bowel surgery. Any bowel surgery has possible risks and discomforts. Your doctor will explain these risks to you. Participation in the ALLEGRO study will not change these risks. We do not anticipate that intravenous lidocaine will have any adverse effects in your overall recovery.
When taking any medicine there is always a very small risk of side-effects or allergies. Local anaesthetics such as lidocaine have been used every day in NHS hospitals and dentist practices for decades. Adverse reactions to lidocaine are rare but may include allergic reaction (including rash, swelling and blistering), • Dizziness, light-headedness, confusion, drowsiness, numbness of the mouth and/or tongue, blurred or double vision, breathlessness, hearing disorders (e.g. ringing in the ear), nausea and vomiting. The signs and symptoms of toxicity (overdose) are well known and treatable. If toxicity occurs during the infusion, you will be in the operating room or recovery room and under very close monitoring as part of normal care. There are no known late side-effects of lidocaine.

Where is the study run from?
Western General Hospital, Edinburgh, UK.

When is the study starting and how long is it expected to run for?
June 2017 to June 2020.

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Sarah Cameron, sarah.cameron@abdn.ac.uk

Trial website

https://w3.abdn.ac.uk/hsru/ALLEGRO/Public/Public/index.cshtml

Contact information

Type

Scientific

Primary contact

Mr Hugh Paterson

ORCID ID

Contact details

Western General Hospital
Colorectal Surgery Unit
Crewe Road
Edinburgh
EH4 2XU
Edinburgh
EH4 2XU
United Kingdom

Additional identifiers

EudraCT number

2017-003835-12

ClinicalTrials.gov number

Protocol/serial number

AC17067

Study information

Scientific title

A placebo-controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery

Acronym

ALLEGRO

Study hypothesis

The primary aim is an effectiveness analysis to measure whether perioperative intravenous lidocaine achieves faster return of gut function for more patients after colorectal surgery. An initial internal pilot phase will be built into the trial to assess feasibility of recruitment.

Ethics approval

West of Scotland Research Ethics Service (WoSRES), 31/10/2017, 17/WS/0210

Study design

Multicentre double-blind parallel-group placebo-controlled randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Colorectal resection for colorectal cancer or diverticular disease.

Intervention

Participants scheduled to undergo laparoscopic colectomy will be randomised on a 1:1 basis to either lidocaine or placebo. The participants will receive an intravenous bolus over 20 minutes of lidocaine hydrochloride 2% solution for injection at a dose of 1.5 mg/kg ideal body weight or placebo (0.9% sterile sodium chloride solution for injection) at induction of anaesthesia followed by intravenous infusion of lidocaine at1.5 mg/kg/hour ideal body weight with a maximum rate of 120 mg/hour or placebo for a minimum of 6 hours up to a maximum of 12 hours.

Intervention type

Drug

Phase

Not Specified

Drug names

lidocaine

Primary outcome measure

Proportion of randomised subjects who have achieved return of gut function at 72 hours postoperatively. This will be measured by ‘GI-3 recovery’, a composite endpoint defined as achievement of both of the following two events: tolerating diet (defined as ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals) and passage of flatus or stool (whichever comes first).

Secondary outcome measures

1. Time from start of operation to return of gut function using the GI-3 recovery definition (a composite endpoint defined as time from surgery to the later time to establish both of the following two events: tolerating diet without significant nausea or vomiting for 3 consecutive meals and first passage of flatus or stool) assessed using patient case report form (CRF) from medical notes
2. GI-2 recovery (defined as the time from start of operation to achieving both of the following two events: tolerating diet [defined as ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals] and passage of stool) assessed using patient CRF from medical notes
3. Rate of prolonged postoperative ileus (PPOI), defined as failure to establish GI-3 by 120 hours after surgery (postoperative day 5) assessed using patient CRF from medical notes
4. Postoperative nausea and vomiting (PONV), including daily PONV score, number of episodes of vomiting (defined as episodes of expulsion of gastric content) and total dosage of rescue antiemetic in 72 hours after the start of the operation assessed using PONV questionnaire
5. Quality of analgesia using OBAS score daily in-hospital up to and including postoperative day 7
6. Total postoperative opioid consumption in morphine equivalent doses until 72 hours after start of operation, assessed using patient notes and recorded in CRF
7. Quality of recovery score assessed using a 15-question patient-reported outcome measure (PROM) questionnaire completed by patients daily while in hospital up to 7 days and at postoperative days 7 and 30
8. Quality of life assessed using EQ-5D questionnaire completed by patients daily while in hospital up to 7 days and at postoperative days 7, 30 and 90
9. Enhanced Recovery After Surgery protocol compliance measured by recording specific variables relevant to return of gut function from end of surgery until end of in-patient admission using medical records. The protocol items are:
9.1. Avoidance of long-acting opioids for maintaining anaesthesia
9.2. Prescribed PONV prophylaxis for 48 hours
9.3. Restrictive IV fluid policy aiming for euvolaemia, assessed by total IV fluid administration in 24 hours from start of anaesthesia and measuring patient weight pre- and 24 hours post operation.
9.4. Early feeding, with a carbohydrate supplement drink on day of surgery and solid food from postoperative day 1 onwards
9.5. Early mobilisation - patients should be out of bed for 2 hours on day of surgery and 4-6 hours every day thereafter AND walking
9.6. Routine postoperative laxative prescription
9.7. No nasogastric tube immediately after surgery
10. Time to achievement of medically-defined hospital discharge criteria (independent hydration/nutrition, adequate analgesia by oral route, independent mobilisation, return of gut function by GI-3 definition, no medical contraindication) recorded in patient CRF from patient medical notes
11. Time (days) to patient-reported readiness for discharge (must also have achieved medical criteria for discharge as noted above) assessed daily from day 2 onward using patient CRF from medical notes
12. Health economic evaluation with outcome measures determined through a model scoping exercise





Overall trial start date

01/06/2017

Overall trial end date

30/06/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Scheduled for elective colorectal resection for colorectal cancer or diverticular disease at participating UK colorectal surgery units. Right hemicolectomy, extended right hemicolectomy, left colectomy, sigmoid colectomy, subtotal colectomy with ileosigmoid or ileorectal anastomosis and high anterior resection are eligible.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

562

Participant exclusion criteria

1. Planned epidural anaesthesia
2. Planned regional or local infiltration of lidocaine at the same time as lidocaine infusion
3. Pregnancy
4. Breastfeeding
5. Patients lacking capacity to give informed consent
6. Known or suspected allergy to lidocaine or amide-type local anaesthetics
7. Current complete heart block
8. Current severe liver dysfunction (Child’s A or greater)
9. Current renal failure (eGFR <30)
10. Participation in the active intervention phase of another therapeutic clinical trial (or other interventional trial) unless a co-enrolment agreement is in place
11. Patients having surgery for indications other than colorectal cancer/diverticular disease
12. Rectal cancer below the peritoneal reflection in which total mesorectal excision is anticipated
13. Rectal cancer patients who have received any neoadjuvant radiotherapy
14. Preoperative surgical plan to form any new stoma during the primary procedure

Recruitment start date

01/11/2017

Recruitment end date

28/06/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Western General Hospital NHS Lothian
Edinburgh
EH4 2XU
United Kingdom

Sponsor information

Organisation

ACCORD

Sponsor details

Research Governance and QA office
University of Edinburgh
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/06/2021

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/06/2018: A participant information sheet has been uploaded.