Trial Outcomes & Findings for Prospective, Randomized Controlled Trial on Perioperative Pregabalin to Reduce Late-onset CRPS After TKA (NCT NCT00558753)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

240 participants

Primary outcome timeframe

36 h

Results posted on

2016-05-26

Participant Flow

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.

There were 110 Screen Failures (31 Not meeting inclusion criteria, 79 eligible but did not give consent), resulting in 240 enrolled subjects.

Participant milestones

Participant milestones
Measure	1 Placebo Half of the patients will receive oral (PO) placebo for 14 days	2 Pregabalin 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 Study STARTED	120	120
Overall Study COMPLETED	115	113
Overall Study NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	1 Placebo Half of the patients will receive oral (PO) placebo for 14 days	2 Pregabalin 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 Study Lost to Follow-up	5	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Placebo n=120 Participants Half of the patients will receive PO placebo for 14 days	2 Pregabalin n=120 Participants 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 n=240 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 8.9 • n=5 Participants	64.0 years STANDARD_DEVIATION 8.3 • n=7 Participants	63.7 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	91 Participants n=7 Participants	175 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	29 Participants n=7 Participants	65 Participants n=5 Participants
BMI	34.6 kg/m^2 STANDARD_DEVIATION 7.7 • n=5 Participants	34.2 kg/m^2 STANDARD_DEVIATION 8.4 • n=7 Participants	34.4 kg/m^2 STANDARD_DEVIATION 8 • n=5 Participants

PRIMARY outcome

Timeframe: 36 h

Population: Because of structural missing data, sample sizes are smaller than the samples size for the secondary measure.

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.

Outcome measures

Outcome measures
Measure	1 Placebo n=76 Participants Half of the patients will receive PO placebo for 14 days	2 Pregabalin n=70 Participants 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.
Epidural Medication Consumption Rate	6.40 mL/h Standard Deviation 1.26	5.77 mL/h Standard Deviation 1.31

SECONDARY outcome

Timeframe: 3 and 6 months post-surgery

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.

Outcome measures

Outcome measures
Measure	1 Placebo n=115 Participants Half of the patients will receive PO placebo for 14 days	2 Pregabalin n=113 Participants 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.
Neuropathic Pain (S-LANSS > 12) Neuropathic pain at 3 Month Follow up	10 participants	0 participants
Neuropathic Pain (S-LANSS > 12) Neuropathic pain at 6 Month Follow up	6 participants	0 participants

SECONDARY outcome

Timeframe: 1-30 days

Outcome measures

Outcome measures
Measure	1 Placebo n=89 Participants Half of the patients will receive PO placebo for 14 days	2 Pregabalin n=73 Participants 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.
Knee Range of Motion (Active Flexion) Day 1	75.6 Degrees Standard Error 1.5	77.8 Degrees Standard Error 1.6
Knee Range of Motion (Active Flexion) Day 2	76.7 Degrees Standard Error 1.3	81.0 Degrees Standard Error 1.4
Knee Range of Motion (Active Flexion) Day 3	80.4 Degrees Standard Error 1.5	84.2 Degrees Standard Error 1.6
Knee Range of Motion (Active Flexion) Day 30	103.0 Degrees Standard Error 1.3	107.2 Degrees Standard Error 1.4

Adverse Events

1 Placebo

Serious events: 0 serious events

Other events: 65 other events

Deaths: 0 deaths

2 Pregabalin

Serious events: 0 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	1 Placebo n=120 participants at risk Half of the patients will receive PO placebo for 14 days	2 Pregabalin n=120 participants at risk 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.
General disorders Sedation	23.3% 28/120	29.2% 35/120
Gastrointestinal disorders Confusion	7.5% 9/120	12.5% 15/120
General disorders Dizziness	13.3% 16/120	20.8% 25/120
Gastrointestinal disorders Headache	0.00% 0/120	2.5% 3/120
General disorders Dry Mouth	2.5% 3/120	7.5% 9/120
General disorders Nausea	22.5% 27/120	14.2% 17/120
General disorders Vomiting	8.3% 10/120	7.5% 9/120
General disorders Itching	10.8% 13/120	5.0% 6/120

Additional Information

Asokumar Buvanendran, M.D.

Rush University Medical Center

Phone: (312) 942-3685

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place