Gabapentin in post-surgery pain
| ISRCTN | ISRCTN63614165 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63614165 |
| EudraCT/CTIS number | 2017-002078-38 |
| Secondary identifying numbers | SU/2016/6033 |
- Submission date
- 05/06/2017
- Registration date
- 05/06/2017
- Last edited
- 26/05/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Gabapentin is a medicine used to treat epilepsy and nerve pain. Recently, doctors have begun using gabapentin to treat pain after an operation with the intention of reducing the amount of other drugs needed while maintaining good pain relief. Opioid drugs, such as morphine, are the most commonly used drugs to control pain after surgery, but doctors want to try to reduce the amount of opioid drugs because they cause side effects, often delaying discharge from hospital and leading to slower recovery. There is uncertainty about whether adding gabapentin to the usual drug regimen (which includes opioid drugs) will result in good pain relief, fewer side effects overall and faster recovery after surgery. The aim of this study is to find out whether gabapentin reduces the amount of time patients stay in hospital after the operation, the amount of opioid medication they take, and to assess how gabapentin influences pain in hospital and four months after surgery.
Who can participate?
Adults who are undergoing non-emergency heart, lungs or abdominal surgery
What does the study involve?
Participants are randomly allocated into one of two groups. Those in the first group are treated with gabapentin one hour before surgery and for two days after surgery. Those in the second group are treated with an identical looking dummy pill (placebo) at the same timepoints. Pain levels are assessed by asking patients one, four and 12 hours after surgery and then twice a day until they are discharged from hospital. Patients are also followed up until discharge to find out if they have taken opioid pain killers, as well as to assess their quality of life after four weeks and four months.
What are the possible benefits and risks of participating?
There are no guaranteed benefits of participating, however those who receive the gabapentin may have fewer side effects from opioid drugs and may recover from surgery more quickly. The results from this study may help improve management of pain after surgery in the future. Risks of taking part in the study include the risks of side effects from gabapentin. The side effects of gabapentin are usually short lived and will stop when the medication is stopped. These side effects have only been observed in patients who take gabapentin over long periods of time (e.g. to treat epilepsy or long-term pain). Gabapentin is usually well tolerated and it is unlikely that these events will occur in this study where gabapentin is only taken for a short period of time.
Where is the study run from?
Trials Unit: Bristol Trials Centre (Clinical Trials and Evaluation Unit), Bristol (UK)
Sponsor: University Hospitals Bristol & Weston NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
June 2017 to January 2023
Who is funding the study?
National Institute for Health Research, Health Technology Assessment Programme (UK)
Who is the main contact?
Professor Chris Rogers
Chris.Rogers@bristol.ac.uk
Contact information
Scientific
Clinical Trials and Evaluation Unit
Bristol Royal Infirmary
Level 7
Marlborough Street
Bristol
BS2 8HW
United Kingdom
| Phone | +44 117 342 2507 |
|---|---|
| Chris.Rogers@bristol.ac.uk |
Study information
| Study design | Multi-centre parallel group placebo-controlled pragmatic randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN63614165_PIS_v3.0_25May18.pdf |
| Scientific title | Effectiveness, cost effectiveness and safety of gabapentin versus placebo as an adjunct to multimodal pain regimens in surgical patients: A placebo controlled randomised controlled trial with blinding (The GAP study) |
| Study acronym | GAP Study |
| Study objectives | Gabapentin reduces opioid use after surgery and speeds up recovery, thereby reducing post-operative hospital stay compared to standard multimodal analgesia (usual care). |
| Ethics approval(s) | Yorkshire and the Humber – Sheffield REC, 23/11/2017, REC ref: 17/YH/0381 |
| Health condition(s) or problem(s) studied | Pain management after surgery |
| Intervention | Participants are randomised in a 1:1 ratio to one of two groups by an authorised member of the local research team using a secure internet-based randomisation system ensuring allocation concealment. Intervention group: Participants receive gabapentin 600 mg given preoperatively with the patient’s premedication and 600 mg/day (300 mg in the morning and 300 mg in the evening) given postoperatively for two days following extubation (if applicable) within the multimodal analgesic regimens specified by local analgesic protocols. Control group: Participants receive a placebo which will be taken at the same time points as the active tablet within the multimodal analgesic regimens specified by local analgesic protocols. Patients in both groups are followed up at approximately four weeks and four months after randomisation for information on pain, adverse events, resource use and quality of life. this information will be collected via postal questionnaires and/or over the phone. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Gabapentin |
| Primary outcome measure | Time from start of surgery to hospital discharge is measured by reviewing participant hospital notes at discharge. |
| Secondary outcome measures | 1. Opioid consumption in the period from surgery until hospital discharge is measured by reviewing participant hospital notes at hospital discharge 2. Acute post-operative pain is assessed using the visual analogue scale (VAS) completed at 1, 4 and 12 hours post-surgery and then twice daily to discharge 3. Adverse health events from randomisation to 4 months including side effects of medication (e.g. nausea; vomiting; pruritus; sedation; confusion) and on-going pain are assessed by reviewing participant hospital notes throughout their hospital stay and at discharge, as well as phone calls with the participants at 4 weeks and 4 months after randomisation 4. HRQoL measured using the EQ-5D 5 level questionnaire and Short-form (SF) 12 completed at baseline and at follow-up at approximately 4 weeks and 4 months after randomisation 5. Resource use to 4 months is measured by reviewing participant hospital notes and completion of Resource Use Questionnaires during the hospital stay, at 4 weeks and 4 months 6. Chronic pain is measured using the brief pain inventory (BPI) at baseline and at 4 months after randomisation |
| Overall study start date | 01/06/2017 |
| Completion date | 31/01/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1180 |
| Total final enrolment | 1196 |
| Key inclusion criteria | Current inclusion criteria as of 18/01/2019: 1. Over 18 years of age 2. Undergoing non-emergency surgery: 2.1. Cardiac (surgery on the heart and great vessels carried out via midline sternotomy) 2.2. Thoracic surgery (open or minimal access surgery on the lungs and surrounding tissues) 2.3. Abdominal (open or minimal access surgery within the abdominal cavity) 3. Expected to stay in hospital at least until day 2 after surgery (day 0 is day of surgery) 4. Expected to be able to swallow during the time of the study intervention Previous inclusion criteria: 1. Over 18 years of age 2. Undergoing non-emergency surgery: 2.1. Cardiac (surgery on the heart and great vessels carried out via midline sternotomy) 2.2. Thoracic surgery (surgery on the lungs and surrounding tissues) 2.3. Abdominal (open or laparoscopic surgery within the abdominal cavity) |
| Key exclusion criteria | Current exclusion criteria as of 18/01/2019: 1. Taking anti-epileptic medication(s) 2. Allergy to gabapentin 3. Already taking gabapentin or gabapentanoids 4. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption 5. Planned epidural analgesia 6. Intended use of any gabapentanoids in the peri-operative analgesic protocol other than the study medication (this includes but is not restricted to: pregabalin, enacarbil gabapentin, 4-methylpregabalin and phenibut) 7. Known renal impairment (for such patients, estimated glomerular filtration rate (eGFR) 8. Weight <50kg 9. Inability to provide written informed consent to participate in the trial 10. Unwilling to participate in follow-up 11. Prisoners 12. Enrolled in another clinical trial and: a) the patient is currently taking an investigational medicinal product as part of the other trial; or b) co-enrolment is not permitted by the other trial; or c) co-enrolment would be burdensome for the patient Previous exclusion criteria: 1. Expected to have a minimum length of hospital stay of less than 2 days 2. Taking anti-epileptic medication(s) 3. Allergy to gabapentin 4. Planned epidural analgesia 5. Intended use of any gabapentanoids in the peri-operative analgesic protocol other than the study medication (this includes but is not restricted to: pregabalin, enacarbil gabapentin, 4-methylpregabalin and phenibut) 6. Known renal impairment (for such patients, estimated glomerular filtration rate (eGFR) <30ml/min/1.732) 7. Weight <50kg 8. Inability to provide written informed consent to participate in the trial 9. Unwilling to participate in follow-up 10. Prisoners 11. Already taking gabapentin or gabapentanoids 12. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption 13. Currently taking an investigational medicinal product as part of another clinical trial |
| Date of first enrolment | 24/04/2018 |
| Date of final enrolment | 20/05/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Marlborough Street
Bristol
BS2 8HW
United Kingdom
Southampton
SO16 6YD
United Kingdom
Taunton
TA1 5DA
United Kingdom
Basildon
SS16 5NL
United Kingdom
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom
Bath
BA1 3NG
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Sponsor information
Hospital/treatment centre
Research and Innovation
Level 3, Education Centre
Upper Maudlin Street
Bristol
BS2 8AE
England
United Kingdom
"ROR" |
https://ror.org/04nm1cv11 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from the CTEU team on bristol-cteu@bristol.ac.uk. Please also note that anonymised data will be provided on request for ethically approved research. All such requests could be subject to a small charge to cover the costs of preparing the files and associated documentation. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v3.0 | 25/05/2018 | 18/01/2019 | No | Yes |
| Protocol article | protocol | 20/11/2020 | 15/01/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN63614165_PIS_v3.0_25May18.pdf
- Uploaded 18/01/2019
Editorial Notes
26/05/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/05/2022 to 20/05/2022.
2. The total final enrolment number has been added.
3. The trial participating centre “Liverpool University Hospitals NHS Foundation Trust” has been added.
18/01/2021: Internal review.
15/01/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2020 to 31/05/2022.
2. The overall trial end date has been changed from 01/06/2021 to 31/01/2023.
3. The intention to publish date has been changed from 01/06/2022 to 31/01/2024.
4. Publication reference added.
5. The target number of participants and the total target enrolment has been changed from 1500 to 1180.
6. The trial participating centre has been updated from "University Hospitals Bristol NHS Foundation Trust" to "University Hospitals Bristol & Weston NHS Foundation Trust".
7. The plain English summary has been updated to reflect the changes above.
21/08/2020: The recruitment end date has been changed from 01/08/2020 to 31/12/2020.
27/01/2020: Musgrove Park Hospital, Basildon University Hospital, Blackpool Victoria Hospital and Royal United Hospital have been added to the trial participating centres.
18/01/2019: The following changes were made to the trial record:
1. Trial website, ethics approval information added.
2. Inclusion/exclusion criteria updated.
3. The recruitment start date was changed from 01/02/2018 to 24/04/2018.
4. The participant information sheet has been uploaded.
06/06/2017: Verified study information with principal investigator.
