Chronic Postoperative PainPhase 4NCT01296347
Low Dose Peri-operative IV Ketamine for Chronic Post-surgery Pain Prevention
A Phase 4 study testing Ketamine in people with Chronic Postoperative Pain, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Postoperative Pain
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2011to Jul 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W2 1NY
About this study
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)
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.
Read the 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.
- Conditions
- Chronic Postoperative Pain
- Being tested
- Ketamine
- Keywords
- Ketamine, Thoracotomy, VATS, Pain
- Medical subject headings
- Pain, Postoperative, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
Intravenous infusion of ketamine starting 10 minutes prior to surgery and running for 96 hours, which will be administered at a rate of 0.1mg/kg/hour. A loading dose of 0.1mg/kg will be administered prior to the start of the infusion
| Study group | Role | What they receive |
|---|---|---|
| Saline | No intervention | Patients will receive a placebo infusion of 0.9% sodium chloride, which will start 10 minutes prior to the start of the operation and continue for 96 hours. |
| ketamine | Experimental | Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Score on Moving at 6 Weeks
Measures in pain include:
Numeric pain score of 0 to 10. Zero denotes 'no pain'; 10 denotes 'pain as bad as you can imagine'
Measured: 6 weeks after surgery
Secondary outcomes (6)
Analgesic Consumption (Opioid)
Analgesia consumption will be measured post-operatively and at 6 weeks
Measured: 6 weeks, 3 month, 6 month
Sensory Testing
Hypoaesthesia: light touch of the blunt end of a paintbrush was felt less precisely, than in healthy tissue.
Hyperalgesia: the pain induced by a sterile neurotip, applied perpendicular to the skin is felt abnormally strongly, in comparison to the contralateral side.
Static allodynia: the application of a Von Frey hair number 14. (8g) was unpleasant, in comparison to the contralateral side.
Dynamic allodynia: three successive gentle strokes of an 8 mm-wide paintbrush over a 40 mm distance, is unpleasant, in comparison to the contralateral side.
Measured: 6 weeks, 6 months, 12 months
Incidence of Side-effects, Nausea
The presence of nausea recorded at the above time points
Measured: 108 hours
Incidence of Side Effect, Vomiting
The presence of vomiting recorded at the above time points
Measured: 108 hours
Incidence of Side Effect, Lightheaded
The presence of lightheaded recorded at the above time points
Measured: 108 hours
Incidence of Side Effect, Vivid Dreams
The presence of vivid dreams recorded at the above time points
Measured: 108 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2011 (estimated)
- Study startApr 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Postoperative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Principal investigator, Gillian Chumbley, Imperial College Healthcare NHS Trust
- Investigators
- Gillian M Chumbley, BSc, PhD, Principal investigator, Imperial Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01296347
- Sponsor's protocol ID
- Chumbley1
- Status last verified
- Aug 2019
- First submitted
- 31 Jan 2011
- Last updated
- 4 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 30719817
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01296347
- Acronym / sponsor ID
- Chumbley1
- Conditions
- Chronic Postoperative Pain
- Keywords
- Ketamine, Thoracotomy, VATS, Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Study start
- Apr 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 15 Feb 2011 (estimated)
- Results
- Posted 14 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saline | No intervention | –Patients will receive a placebo infusion of 0.9% sodium chloride, which will start 10 minutes prior to the start of the operation and continue for 96 hours. |
| ketamine | Experimental | Drug: KetaminePatients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: KetalarIntravenous infusion of ketamine starting 10 minutes prior to surgery and running for 96 hours, which will be administered at a rate of 0.1mg/kg/hour. A loading dose of 0.1mg/kg will be administered prior to the start of the infusion | Drug | ketamine |
Primary outcome
Pain Score on Moving at 6 Weeks
Time frame: 6 weeks after surgery
Measures in pain include: Numeric pain score of 0 to 10. Zero denotes 'no pain'; 10 denotes 'pain as bad as you can imagine'
6 secondary outcomes
Analgesic Consumption (Opioid)
Time frame: 6 weeks, 3 month, 6 month
Sensory Testing
Time frame: 6 weeks, 6 months, 12 months
Incidence of Side-effects, Nausea
Time frame: 108 hours
Incidence of Side Effect, Vomiting
Time frame: 108 hours
Incidence of Side Effect, Lightheaded
Time frame: 108 hours
Incidence of Side Effect, Vivid Dreams
Time frame: 108 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30719817Chumbley 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gillian M Chumbley, BSc, PhD principal investigator
Imperial Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine in people with Chronic Postoperative Pain, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Score on Moving at 6 Weeks (time frame: 6 weeks after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01296347, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019.