Plain English Summary
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?
1. University Hospitals Bristol NHS Foundation Trust (UK)
2. University Hospitals Southampton NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
June 2017 to June 2021
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
Trial website
Contact information
Type
Scientific
Primary contact
Prof Chris Rogers
ORCID ID
Contact details
Clinical Trials and Evaluation Unit
Bristol Royal Infirmary
Level 7
Marlborough Street
Bristol
BS2 8HW
United Kingdom
+44 117 342 2507
Chris.Rogers@bristol.ac.uk
Additional identifiers
EudraCT number
2017-002078-38
ClinicalTrials.gov number
Protocol/serial number
SU/2016/6033
Study information
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)
Acronym
GAP Study
Study hypothesis
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
Not provided at time of registration
Study design
Multi-centre parallel group placebo-controlled pragmatic randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Phase IV
Drug names
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 trial start date
01/06/2017
Overall trial end date
01/06/2021
Reason abandoned (if study stopped)
Eligibility
Participant 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)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1500
Participant 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
Recruitment start date
01/02/2018
Recruitment end date
01/08/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospitals Bristol NHS Foundation Trust
Bristol Royal Infirmary
Marlborough Street
Bristol
BS2 8HW
United Kingdom
Trial participating centre
University Hospitals Southampton NHS Foundation Trust
Tremona Road
Southampton
SO16 6YD
United Kingdom
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
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 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.
Intention to publish date
01/06/2022
Participant level data
Available on request
Basic results (scientific)
Publication list