Clinical trial NCT01296347: Low Dose Peri-operative IV Ketamine for Chronic Post-surgery Pain Prevention
Official title: A Double-blind, Randomised Placebo-controlled Trial to Determine Whether Low-dose Intravenous Ketamine Peri-operatively Can Prevent Chronic Post-surgical Pain, in Patients Undergoing Thoracotomy or Video Assisted Thoracic Surgery (VATS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Postoperative Pain
Keywords: Ketamine
Thoracotomy
VATS
Pain
Lead sponsor: Imperial College Healthcare NHS Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2011-02-15
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will test the null hypothesis that low-dose ketamine given peri-operatively will have no effect on the development of chronic post-surgical pain, in patients undergoing thoracotomy or video assisted thoracic surgery (VATS) procedures

A double-blind, randomised placebo-controlled trial will be used to test the null hypothesis. Potential participants due to undergo either thoracotomy or video assisted thoracic surgery (VATS) will be identified by the collaborating thoracic surgeons in the out-patient department. Patients will be sent information about the study by post, prior to admission for surgery. If they are willing to participate, written consent will be sought on the ward preoperatively, where they will complete baseline measures of pain.

Patients will be randomised to receive an intravenous infusion of placebo (saline) or ketamine running at 0.1mg/kg/hour, starting 10 minutes prior to the surgical incision and continuing for the first three postoperative days (96 hours in total). Prior to starting the infusion a loading dose of ketamine (0.1 mg per kg) will be administered.

Detailed description: This study will test the null hypothesis that low-dose ketamine given peri-operatively will have no effect on the development of chronic post-surgical pain, in patients undergoing thoracotomy or video assisted thoracic surgery (VATS) procedures

A double-blind, randomised placebo-controlled trial will be used to test the null hypothesis. Potential participants due to undergo either thoracotomy or video assisted thoracic surgery (VATS) will be identified by the collaborating thoracic surgeons in the out-patient department. Patients will be sent information about the study by post, prior to admission for surgery. If they are willing to participate, written consent will be sought on the ward preoperatively, where they will complete baseline measures of pain.

Patients will be randomised to receive an intravenous infusion of placebo (saline) or ketamine running at 0.1mg/kg/hour, starting 10 minutes prior to the surgical incision and continuing for the first three postoperative days (96 hours in total). Prior to starting the infusion a loading dose of ketamine (0.1 mg per kg) will be administered. All staff, including the anaesthetist, surgical team, ward nurses and the principal investigator will be blind to the treatment given throughout the study. The key to the randomisation will be revealed at the end of the study.

Patients will be asked to complete a numeric pain score (NPS) and standard pain questionnaires which includes the Brief Pain Inventory \[BPI\], short form Leeds Assessment of Neuropathic Symptoms and Signs \[S-LANSS\]) prior to surgery, then at 6 weeks, 3, 6 and 12 months after surgery. The surgical area will also be examined at 6 weeks, 6 and 12 months for signs of neuropathic or nerve pain. Whilst in hospital patients will be asked to score their pain daily, on a numeric pain scale of 0 to 10. Consumption of morphine and side-effects will be recorded.

Patients will receive standard post-operative analgesia.

A sample size calculation based on a previous study, to detect a reduction in pain of 2 points the 10 point numeric pain scale at the 6 week assessment, with α = 5%, 1 - β = 90% and a bilateral hypothesis, would require a sample size of 36 per group, 72 patients in total. This will require a total study population of 144 patients, as both video assisted thoracic surgery (VATS) and thoracotomy patients will be studied.

A two samples t-test will be used to compare the numeric pain scores between the ketamine and placebo groups at each time point. If these data are not normally distributed then the Mann Whitney test will be used. The scores from the Brief Pain Inventory (BPI) and short form Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) will be analysed in the same manner. The Chi Squared test will be used to compare dichotomous data, such as the incidence of side-effects.

Eligibility criteria: Inclusion Criteria:

* All adult patients (18 years and above) who are undergoing either thoracotomy or video assisted thoracic surgery (VATS).
* Participants must be able to understand English.

Exclusion Criteria:

* Patient refusal
* History of previous chronic thoracic pain
* Neuropathic pain (whatever the site), existing at time of recruitment
* Pre-operative analgesic treatments which include the following medications: strong opioids (step 3 analgesics), tricyclic antidepressants, venlafaxine, gabapentin, pregabalin, duloxetine, clonazepam or carbamazepine.
* Allergy to bupivacaine, morphine, paracetamol, tramadol, dihydrocodeine or ketamine.

Primary outcomes:
measure: Pain Score on Moving at 6 Weeks
timeFrame: 6 weeks after surgery
Secondary outcomes:
measure: Analgesic Consumption (Opioid)
timeFrame: 6 weeks, 3 month, 6 month
measure: Sensory Testing
timeFrame: 6 weeks, 6 months, 12 months
measure: Incidence of Side-effects, Nausea
timeFrame: 108 hours
measure: Incidence of Side Effect, Vomiting
timeFrame: 108 hours
measure: Incidence of Side Effect, Lightheaded
timeFrame: 108 hours
measure: Incidence of Side Effect, Vivid Dreams
timeFrame: 108 hours
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial Healthcare NHS Trust
name: Gillian M Chumbley, BSc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chumbley GM, Thompson L, Swatman JE, Urch C. Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain. Eur J Pain. 2019 May;23(5):985-993. doi: 10.1002/ejp.1366. Epub 2019 Feb 4.