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Low Dose Peri-operative IV Ketamine for Chronic Post-surgery Pain Prevention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01296347
Recruitment Status : Completed
First Posted : February 15, 2011
Results First Posted : April 14, 2017
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Gillian Chumbley, Imperial College Healthcare NHS Trust

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Chronic Postoperative Pain
Intervention Drug: Ketamine
Enrollment 77
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Saline Ketamine
Hide Arm/Group Description 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.

Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours

Ketamine: 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

Period Title: Allocation
Started 38 39
Completed 35 35
Not Completed 3 4
Reason Not Completed
Withdrawal by Subject             1             2
Lack of Efficacy             1             2
not received infusion             1             0
Period Title: 6 Week Follow up
Started 35 35
Completed 35 34
Not Completed 0 1
Reason Not Completed
Death             0             1
Period Title: 3 Month Follow up
Started 35 34
Completed 34 33
Not Completed 1 1
Reason Not Completed
Death             1             0
Lost to Follow-up             0             1
Period Title: 6 Month Follow up
Started 34 33
Completed 32 31
Not Completed 2 2
Reason Not Completed
Death             2             1
Lost to Follow-up             0             1
Period Title: 12 Month Follow up
Started 32 31
Completed 28 28
Not Completed 4 3
Reason Not Completed
Lost to Follow-up             3             1
Death             1             1
Withdrawal by Subject             0             1
Arm/Group Title Saline Ketamine Total
Hide Arm/Group Description 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.

Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours

Ketamine: 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

Total of all reporting groups
Overall Number of Baseline Participants 35 35 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants 35 participants 70 participants
68
(48 to 87)
61
(26 to 77)
64.5
(26 to 87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
Female
23
  65.7%
15
  42.9%
38
  54.3%
Male
12
  34.3%
20
  57.1%
32
  45.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 35 participants 35 participants 70 participants
35 35 70
1.Primary Outcome
Title Pain Score on Moving at 6 Weeks
Hide Description

Measures in pain include:

Numeric pain score of 0 to 10. Zero denotes 'no pain'; 10 denotes 'pain as bad as you can imagine'

Time Frame 6 weeks after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Ketamine group one participant did not have data
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the start of the operation and continued for 96 hours.
Patients received intravenous ketamine, starting 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 35 34
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
0
(0 to 0)
1.5
(0 to 4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Analgesic Consumption (Opioid)
Hide Description Analgesia consumption will be measured post-operatively and at 6 weeks
Time Frame 6 weeks, 3 month, 6 month
Hide Outcome Measure Data
Hide Analysis Population Description
Participant who experienced pain.
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the start of the operation and continue for 96 hours.
Patients received intravenous ketamine, started 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 18 18
Median (Inter-Quartile Range)
Unit of Measure: mg
6 weeks
9
(0 to 26)
0
(0 to 21)
3 months
21
(9 to 47)
17
(17 to 17)
6 months
34
(34 to 34)
9
(9 to 9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments 6 weeks
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments 3 month
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments 6 months
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Sensory Testing
Hide Description

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.

Time Frame 6 weeks, 6 months, 12 months
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Incidence of Side-effects, Nausea
Hide Description The presence of nausea recorded at the above time points
Time Frame 108 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the start of the operation and continue for 96 hours.
Patients received intravenous ketamine, starting 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
14
  40.0%
17
  48.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Incidence of Side Effect, Vomiting
Hide Description The presence of vomiting recorded at the above time points
Time Frame 108 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the started of the operation and continue for 96 hours.
Patients received intravenous ketamine, started 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
8
  22.9%
8
  22.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Incidence of Side Effect, Lightheaded
Hide Description The presence of lightheaded recorded at the above time points
Time Frame 108 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the started of the operation and continue for 96 hours.
Patients received intravenous ketamine, started 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
5
  14.3%
14
  40.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Incidence of Side Effect, Vivid Dreams
Hide Description The presence of vivid dreams recorded at the above time points
Time Frame 108 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Saline Ketamine
Hide Arm/Group Description:
Patients received a placebo infusion of 0.9% sodium chloride, which started 10 minutes prior to the started of the operation and continue for 96 hours.
Patients received intravenous ketamine, started 10 minutes prior to surgery and continued for 96 hours
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.7%
13
  37.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saline, Ketamine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame 1 year
Adverse Event Reporting Description For 108 hours the ketamine or placebo infusion was running and whilst the patient remained in hospital after surgery
 
Arm/Group Title Saline Ketamine
Hide Arm/Group Description 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.

Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours

Ketamine: 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

All-Cause Mortality
Saline Ketamine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/38 (0.00%)      0/39 (0.00%)    
Hide Serious Adverse Events
Saline Ketamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/38 (21.05%)      9/39 (23.08%)    
Cardiac disorders     
cardiac arrest *  1/38 (2.63%)  1 0/39 (0.00%)  0
Hypotension *  0/38 (0.00%)  0 1/39 (2.56%)  1
Eye disorders     
Hallucination, visual * [1]  2/38 (5.26%)  2 2/39 (5.13%)  2
Psychiatric disorders     
Confusion postoperative *  0/38 (0.00%)  0 0/39 (0.00%)  0
Agitation postoperative *  1/38 (2.63%)  1 0/39 (0.00%)  0
Renal and urinary disorders     
Renal failure * [2]  1/38 (2.63%)  1 0/39 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory tract infection *  3/38 (7.89%)  3 1/39 (2.56%)  1
Bronchial obstruction *  0/38 (0.00%)  0 1/39 (2.56%)  1
Respiratory distress * [3]  0/38 (0.00%)  0 1/39 (2.56%)  1
Lung hypoinflation * [4]  0/38 (0.00%)  0 1/39 (2.56%)  1
Pulmonary embolism *  0/38 (0.00%)  0 1/39 (2.56%)  1
Vocal cord paralysis * [5]  0/38 (0.00%)  0 1/39 (2.56%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Hallucinations experienced post-operatively, mostly thought to be due to opioids
[2]
Patient developed renal failure 13 days after starting trial. Renal biopsy showed undetected myeloma.
[3]
Patient developed respiratory distress after thoracotomy, re-intubated and ventilated
[4]
Lung collapse following thoracotomy for cancer, unable to oxygenate. Death due to respiratory failure.
[5]
Injury post thoracotomy intubation, causing hoarse voice
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Saline Ketamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/38 (89.47%)      39/39 (100.00%)    
Gastrointestinal disorders     
Nausea *  14/38 (36.84%)  14 17/39 (43.59%)  17
Vomiting * [1]  8/38 (21.05%)  8 8/39 (20.51%)  8
Nervous system disorders     
Dizziness * [2]  5/38 (13.16%)  8 14/39 (35.90%)  21
Vivid dreams * [3]  2/38 (5.26%)  2 13/39 (33.33%)  13
Skin and subcutaneous tissue disorders     
Pruritus *  13/38 (34.21%)  13 12/39 (30.77%)  12
*
Indicates events were collected by non-systematic assessment
[1]
Post-operative vomiting
[2]
Patients who felt lightheaded after surgery
[3]
Vivid dreams experienced after surgery
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Gillian Chumbley
Organization: ImperialNHSTrust
Phone: +44 203 311 1000 ext Bleep 5865
EMail: gillian.chumbley@imperial.nhs.uk
Layout table for additonal information
Responsible Party: Gillian Chumbley, Imperial College Healthcare NHS Trust
ClinicalTrials.gov Identifier: NCT01296347    
Other Study ID Numbers: Chumbley1
First Submitted: January 31, 2011
First Posted: February 15, 2011
Results First Submitted: December 7, 2016
Results First Posted: April 14, 2017
Last Update Posted: September 4, 2019