Does intravenous lidocaine speed up gut recovery after large bowel surgery?
| ISRCTN | ISRCTN52352431 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52352431 |
| EudraCT/CTIS number | 2017-003835-12 |
| Secondary identifying numbers | AC17067 |
- Submission date
- 13/06/2018
- Registration date
- 13/06/2018
- Last edited
- 27/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
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 July 2023
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
allegro@abdn.ac.uk
Contact information
Scientific
Western General Hospital
Colorectal Surgery Unit
Crewe Road
Edinburgh
EH4 2XU
United Kingdom
 ORCID ID |
0000-0003-4698-0131 |
|---|---|
| Phone | +44 (0)7780 957402 |
| hugh.paterson@ed.ac.uk |
Public
Centre for Healthcare Randomised Trials (CHaRT)
Health Services Research Unit
University of Aberdeen
3rd Floor Health Sciences Building
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom
| allegro@abdn.ac.uk |
Study information
| Study design | Multicentre double-blind parallel-group placebo-controlled randomised trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN52352431_PIS_V2_13Oct2017.pdf |
| Scientific title | A placebo-controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery |
| Study acronym | ALLEGRO |
| Study objectives | 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(s) | West of Scotland Research Ethics Service (WoSRES), 31/10/2017, 17/WS/0210 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/06/2017 |
| Completion date | 31/07/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 562 |
| Total final enrolment | 590 |
| Key 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. |
| Key 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 |
| Date of first enrolment | 13/08/2018 |
| Date of final enrolment | 30/04/2023 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
EH4 2XU
United Kingdom
Sponsor information
University/education
Research Governance and QA office
University of Edinburgh
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
Edinburgh
EH16 4TJ
Scotland
United Kingdom
"ROR" |
https://ror.org/01x6s1m65 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 14/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V2 | 13/10/2017 | 14/06/2018 | No | Yes |
| Protocol article | 28/01/2022 | 31/01/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 27/11/2024 | 28/11/2024 | Yes | No |
Additional files
- ISRCTN52352431_PIS_V2_13Oct2017.pdf
- Uploaded 14/06/2018
Editorial Notes
27/01/2025: The recruitment start date was changed from 01/11/2017 to 13/08/2018.
28/11/2024: Publication reference added.
18/10/2024: A study contact was updated.
18/09/2024: The following changes were made:
1. The intention to publish date was changed from 14/03/2024 to 14/12/2024.
2. Total final enrolment added.
17/07/2023: The contact confirmed the record is up to date.
04/04/2023: The contact confirmed the record is up to date.
17/01/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/01/2023 to 30/04/2023.
2. The overall end date was changed from 30/04/2023 to 31/07/2023.
3. The intention to publish date was changed from 14/12/2023 to 14/03/2024.
4. The plain English summary was updated to reflect these changes.
15/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 31/01/2023.
2. The overall end date was changed from 30/03/2023 to 30/04/2023.
3. The plain English summary was updated to reflect these changes.
18/02/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/11/2021 to 31/12/2022.
2. The overall trial end date was changed from 01/12/2021 to 30/03/2023 and the plain English summary has been updated to reflect this change.
3. The intention to publish date was changed from 31/08/2022 to 14/12/2023.
31/01/2022: Publication reference added.
20/08/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/08/2021 to 30/11/2021.
2. The overall trial end date was changed from 01/09/2021 to 01/12/2021.
3. The intention to publish date was changed from 31/05/2022 to 31/08/2022.
16/06/2021: The recruitment end date was changed from 30/06/2021 to 30/08/2021.
06/07/2020: The following changes were made to the trial record:
1. The contact details were updated.
2. The recruitment end date was changed from 01/02/2021 to 30/06/2021.
3. The overall trial end date was changed from 01/02/2022 to 01/09/2021.
4. The intention to publish date was changed from 01/02/2023 to 31/05/2022.
23/06/2020: The scientific contact's ORCID has been added.
09/07/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 28/06/2019 to 01/02/2021.
2. The overall end date was changed from 30/06/2020 to 01/02/2022.
3. The intention to publish date was changed from 30/06/2021 to 01/02/2023.
4. The plain English summary was updated to reflect these changes.
14/06/2018: A participant information sheet has been uploaded.
