Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prospective, Randomized Controlled Trial on Perioperative Pregabalin to Reduce Late-onset CRPS After TKA (PregTKA)

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: NCT00558753
Recruitment Status : Completed
First Posted : November 15, 2007
Results First Posted : August 27, 2012
Last Update Posted : May 26, 2016
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Asokumar Buvanendran, Rush University Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition CRPS
Interventions Drug: pregabalin
Drug: Placebo
Enrollment 240
Recruitment Details From August 2006 to August 2007, 350 consecutive patients scheduled to undergo elective primary Total knee arthroplasty (TKA) were contacted and assessed for study eligibility. There were 110 Screen Failures (31 Not meeting inclusion criteria, 79 eligible but did not give consent), resulting in 240 enrolled subjects.
Pre-assignment Details There were 110 Screen Failures (31 Not meeting inclusion criteria, 79 eligible but did not give consent), resulting in 240 enrolled subjects.
Arm/Group Title 1 Placebo 2 Pregabalin
Hide Arm/Group Description Half of the patients will receive oral (PO) placebo for 14 days PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.
Period Title: Overall Study
Started 120 120
Completed 115 113
Not Completed 5 7
Reason Not Completed
Lost to Follow-up             5             7
Arm/Group Title 1 Placebo 2 Pregabalin Total
Hide Arm/Group Description Half of the patients will receive PO placebo for 14 days PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped. Total of all reporting groups
Overall Number of Baseline Participants 120 120 240
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 120 participants 120 participants 240 participants
63.3  (8.9) 64.0  (8.3) 63.7  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 120 participants 240 participants
Female
84
  70.0%
91
  75.8%
175
  72.9%
Male
36
  30.0%
29
  24.2%
65
  27.1%
BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 120 participants 120 participants 240 participants
34.6  (7.7) 34.2  (8.4) 34.4  (8)
[1]
Measure Description: Body Mass Index...........................................
1.Primary Outcome
Title Epidural Medication Consumption Rate
Hide Description Epidural medication consumption was recorded for each 4-h interval from the completion of surgery to the time that the epidural was discontinued (same as the time to achieve hospital discharge criteria). Because the discontinuation time varied from patient to patient (as they achieved physical therapy criteria), the average hourly consumption (total analgesic used divided by the total infusion time) was used as the measure of epidural drug use.
Time Frame 36 h
Hide Outcome Measure Data
Hide Analysis Population Description
Because of structural missing data, sample sizes are smaller than the samples size for the secondary measure.
Arm/Group Title 1 Placebo 2 Pregabalin
Hide Arm/Group Description:
Half of the patients will receive PO placebo for 14 days
PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.
Overall Number of Participants Analyzed 76 70
Mean (Standard Deviation)
Unit of Measure: mL/h
6.40  (1.26) 5.77  (1.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Neuropathic Pain (S-LANSS > 12)
Hide Description Patients will be evaluated in blinded fashion for lower extremity Complex Regional Pain Syndrome(CRPS) at pre-op, 1, 3, and 6 months postsurgery based initially on telephone interviews. An S-LANSS score of 12 or more was an indication of chronic neuropathic pain. Patients with an Self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs(S-LANSS) score of 12 or more at 6 mo came to the physician’s office for a standardized physical examination, which included the S-LANSS examination items (allodynia and hyperalgesia) directly assessed by the physician, plus a pinprick evaluation.
Time Frame 3 and 6 months post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1 Placebo 2 Pregabalin
Hide Arm/Group Description:
Half of the patients will receive PO placebo for 14 days
PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.
Overall Number of Participants Analyzed 115 113
Measure Type: Number
Unit of Measure: participants
Neuropathic pain at 3 Month Follow up 10 0
Neuropathic pain at 6 Month Follow up 6 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments For 3 month followup on incidence of neuropathic pain.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Independence: Chi-squared
Estimated Value 10.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments For 6 month followup on incidence of neuropathic pain.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0139
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Independence: Chi-squared
Estimated Value 6.05
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Knee Range of Motion (Active Flexion)
Hide Description [Not Specified]
Time Frame 1-30 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1 Placebo 2 Pregabalin
Hide Arm/Group Description:
Half of the patients will receive PO placebo for 14 days
PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.
Overall Number of Participants Analyzed 89 73
Least Squares Mean (Standard Error)
Unit of Measure: Degrees
Day 1 75.6  (1.5) 77.8  (1.6)
Day 2 76.7  (1.3) 81.0  (1.4)
Day 3 80.4  (1.5) 84.2  (1.6)
Day 30 103.0  (1.3) 107.2  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments Mixed model test of condition (Placebo v Pregabalin) main effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0133
Comments Test of condition(Placebo v Pregabalin) main effect.
Method Mixed Models Analysis
Comments Mixed model with main effects and time by condition interaction.
Method of Estimation Estimation Parameter Slope
Estimated Value -4.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments Test of Condition Effect (Placebo v Pregabalin) at the 1-day post surgery time point (Slice)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3097
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed model test of Condition Effect (Placebo v Pregabalin) at the 1-day post surgery time point (Slice)
Method of Estimation Estimation Parameter Interaction Slice F-value
Estimated Value 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments Test of Condition Effect (Placebo v Pregabalin) at the 2-day post surgery time point (Slice)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0247
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Interaction Slice F-value
Estimated Value 5.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments Test of Condition Effect (Placebo v Pregabalin) at the 3-day post surgery time point (Slice)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0786
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Interaction Slice F-value
Estimated Value 3.11
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 Placebo, 2 Pregabalin
Comments Test of Condition Effect (Placebo v Pregabalin) at the 30-day post surgery time point (Slice)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Interaction Slice F-value
Estimated Value 5.04
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1 Placebo 2 Pregabalin
Hide Arm/Group Description Half of the patients will receive PO placebo for 14 days PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.
All-Cause Mortality
1 Placebo 2 Pregabalin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
1 Placebo 2 Pregabalin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/120 (0.00%)   0/120 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
1 Placebo 2 Pregabalin
Affected / at Risk (%) Affected / at Risk (%)
Total   65/120 (54.17%)   69/120 (57.50%) 
Gastrointestinal disorders     
Confusion   9/120 (7.50%)  15/120 (12.50%) 
Headache   0/120 (0.00%)  3/120 (2.50%) 
General disorders     
Sedation   28/120 (23.33%)  35/120 (29.17%) 
Dizziness   16/120 (13.33%)  25/120 (20.83%) 
Dry Mouth   3/120 (2.50%)  9/120 (7.50%) 
Nausea   27/120 (22.50%)  17/120 (14.17%) 
Vomiting   10/120 (8.33%)  9/120 (7.50%) 
Itching   13/120 (10.83%)  6/120 (5.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Asokumar Buvanendran, M.D.
Organization: Rush University Medical Center
Phone: (312) 942-3685
Responsible Party: Asokumar Buvanendran, Rush University Medical Center
ClinicalTrials.gov Identifier: NCT00558753     History of Changes
Other Study ID Numbers: ABuv102007
First Submitted: November 14, 2007
First Posted: November 15, 2007
Results First Submitted: January 11, 2012
Results First Posted: August 27, 2012
Last Update Posted: May 26, 2016