Trial Outcomes & Findings for Efficacy And Safety Of Pregabalin For Pain Following Total Knee Replacement (NCT NCT00442546)

Results Overview

The mBPI-SF is a self administered questionnaire developed to assess pain severity and pain interference with functional activities during a 24-hour period prior to evaluation. For the Worst Pain item of the m-BPI-sf scale (11 point Likert scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), subjects were asked to rate their pain by marking an "X" in one of the ten boxes that best described their pain at its worst in the last 24 hours post surgery and at least 12 hours after discontinuation of the peripheral nerve block or neuroaxial block.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

307 participants

Primary outcome timeframe

48 hours after surgery

Results posted on

2021-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin (150 Milligrams [mg]) Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on Post-Operative Day 1 (POD 1).	Pregabalin (300 mg) Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Overall Study STARTED	103	100	104
Overall Study Received Treatment	98	96	98
Overall Study COMPLETED	77	63	71
Overall Study NOT COMPLETED	26	37	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin (150 Milligrams [mg]) Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on Post-Operative Day 1 (POD 1).	Pregabalin (300 mg) Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Overall Study Adverse Event	11	17	13
Overall Study Lost to Follow-up	1	2	1
Overall Study Other	4	9	6
Overall Study Withdrawal by Subject	5	5	7
Overall Study Randomized But Not Treated	5	4	6

Baseline Characteristics

Efficacy And Safety Of Pregabalin For Pain Following Total Knee Replacement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin (150 mg) n=98 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=96 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=98 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.	Total n=292 Participants Total of all reporting groups
Age, Customized 18 to 44 years	1 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	7 participants n=4 Participants
Age, Customized 45 to 64 years	52 participants n=5 Participants	44 participants n=7 Participants	49 participants n=5 Participants	145 participants n=4 Participants
Age, Customized > = 65 years	45 participants n=5 Participants	50 participants n=7 Participants	45 participants n=5 Participants	140 participants n=4 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	61 Participants n=7 Participants	54 Participants n=5 Participants	175 Participants n=4 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	35 Participants n=7 Participants	44 Participants n=5 Participants	117 Participants n=4 Participants

PRIMARY outcome

Timeframe: 48 hours after surgery

Population: Modified Intent-to-Treat (MITT) Population=all ITT subjects who took 12 and 2 hours pre-surgery study medications, had no surgical or anesthetic complications during total knee replacement surgery and had at least 1 post surgery primary efficacy measurement.

The mBPI-SF is a self administered questionnaire developed to assess pain severity and pain interference with functional activities during a 24-hour period prior to evaluation. For the Worst Pain item of the m-BPI-sf scale (11 point Likert scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), subjects were asked to rate their pain by marking an "X" in one of the ten boxes that best described their pain at its worst in the last 24 hours post surgery and at least 12 hours after discontinuation of the peripheral nerve block or neuroaxial block.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=78 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=82 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=75 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Subject Reported Worst Pain Score in Daily Diaries Using the Worst Pain Item of the Modified Brief Pain Inventory - Short Form (m-BPI-sf)	7.041 scores on a scale Standard Error 0.267	6.740 scores on a scale Standard Error 0.264	7.079 scores on a scale Standard Error 0.279

SECONDARY outcome

Timeframe: 24 hours, 48 hours, 72 hours, 96 hours, 120 hours, 144 hours, 168 hours, 192 hours, 216 hours

Population: MITT. There were not enough subjects with data at 168, 192, and 216 hours to calculate least squares mean values.

Total cumulative dose calculated as mg of oral morphine equivalent and included opioids given by any route (patient controlled analgesia \[PCA\] pump, parenteral bolus or oral). Results for daily total not including pregabalin (not an opioid). Statistical model included main effect of treatment group and center. 1 subject at 144 h, 300 mg=non-missing data. Due to small sample size (N=1, 300 mg; N=5, other groups) and large opioid consumption for another subject in same center, least squares mean (300 mg, 144 h) is negative.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=85 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=86 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=84 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 24 hours (n=85, 86, 84)	151.790 mg of oral morphine equivalent Standard Error 14.210	152.306 mg of oral morphine equivalent Standard Error 14.313	167.854 mg of oral morphine equivalent Standard Error 14.573
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 48 hours (n=82, 81, 83)	86.402 mg of oral morphine equivalent Standard Error 12.057	93.846 mg of oral morphine equivalent Standard Error 12.292	122.830 mg of oral morphine equivalent Standard Error 12.304
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 72 hours (n=60, 60, 60)	55.654 mg of oral morphine equivalent Standard Error 9.175	48.713 mg of oral morphine equivalent Standard Error 9.420	52.895 mg of oral morphine equivalent Standard Error 9.851
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 96 hours (n=32, 39, 35)	31.976 mg of oral morphine equivalent Standard Error 7.928	24.758 mg of oral morphine equivalent Standard Error 7.861	35.332 mg of oral morphine equivalent Standard Error 8.354
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 120 hours (n=12, 6, 13)	27.520 mg of oral morphine equivalent Standard Error 13.146	14.235 mg of oral morphine equivalent Standard Error 17.684	27.559 mg of oral morphine equivalent Standard Error 13.306
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay 144 hours (n=5, 1, 5)	33.956 mg of oral morphine equivalent Standard Error 12.019	-64.544 mg of oral morphine equivalent Standard Error 28.633	73.956 mg of oral morphine equivalent Standard Error 16.720

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 6/Early Termination (ET)

Population: MITT

The amount of opioid use was calculated as mg of oral morphine equivalent and included opioids administered by any route (PCA pump, parenteral bolus, or oral). Weeks 2, 4, and 6 total daily doses were calculated by adding the cumulative doses during the 2 week period prior to the visit and dividing them by the number of days in the period. This outcome measure does not include pregabalin as it is not an opioid.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=41 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=40 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=36 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Opioids Used Post Discharge Week 2 (n=41, 40, 36)	30.255 mg of oral morphine equivalent Standard Error 3.515	27.692 mg of oral morphine equivalent Standard Error 3.534	26.119 mg of oral morphine equivalent Standard Error 3.789
Opioids Used Post Discharge Week 4 (n=33, 33, 30)	37.130 mg of oral morphine equivalent Standard Error 4.975	37.507 mg of oral morphine equivalent Standard Error 4.911	34.271 mg of oral morphine equivalent Standard Error 5.274
Opioids Used Post Discharge Week 6/ET (n=24, 28, 22)	38.686 mg of oral morphine equivalent Standard Error 6.261	35.945 mg of oral morphine equivalent Standard Error 5.888	35.036 mg of oral morphine equivalent Standard Error 6.401

SECONDARY outcome

Timeframe: 24 hours, 48 hours, 72 hours

Population: MITT. There were not enough subjects with data to calculate least squares mean values at 24 and 48 hours for Acetylalicyclic Acid and 72 hours for Ketorolac.

Total dose for in-hospital visits was the total dose for the day.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=22 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=25 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=17 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Acetylsalicylic Acid, 72 hours (n=3, 1, 1)	235.175 mg Standard Error 61.531	1442.025 mg Standard Error 117.823	1425.825 mg Standard Error 117.823
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Ketorolac, 24 hours, (n=1, 4, 3)	32.961 mg Standard Error 57.230	53.432 mg Standard Error 28.615	27.189 mg Standard Error 31.346
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Ketorolac, 48 hours, (n=2, 8, 4)	20.553 mg Standard Error 7.971	21.863 mg Standard Error 3.862	23.473 mg Standard Error 5.520
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Paracetamol, 24 hours (n=14, 20, 16)	1311.246 mg Standard Error 359.886	1363.086 mg Standard Error 283.808	1380.481 mg Standard Error 309.224
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Paracetamol, 48 hours (n=22, 25, 17)	1357.030 mg Standard Error 371.095	1368.880 mg Standard Error 339.509	1263.337 mg Standard Error 443.695
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol) Paracetamol, 72 hours (n=12, 13, 16)	446.050 mg Standard Error 445.588	877.916 mg Standard Error 403.657	1128.355 mg Standard Error 347.457

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 6/ET

Population: MITT.

Weeks 2, 4, and 6 total daily doses were calculated by adding the cumulative doses during the 2 week period prior to the visit and dividing them by the number of days in the period.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=7 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=14 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=7 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Analgesics Used Post Discharge (Acetylsalicylic Acid [Week 2] and Paracetamol [Weeks 2, 4, and 6] Acetylsalicylic Acid, Week 2 (n=6, 1, 2)	498.613 mg Standard Error 130.446	797.463 mg Standard Error 361.189	992.613 mg Standard Error 291.687
Analgesics Used Post Discharge (Acetylsalicylic Acid [Week 2] and Paracetamol [Weeks 2, 4, and 6] Paracetamol, Week 2 (n=7, 13, 7)	603.496 mg Standard Error 232.179	665.574 mg Standard Error 164.777	630.787 mg Standard Error 247.693
Analgesics Used Post Discharge (Acetylsalicylic Acid [Week 2] and Paracetamol [Weeks 2, 4, and 6] Paracetamol, Week 4 (n=5, 12, 6)	792.434 mg Standard Error 412.260	779.226 mg Standard Error 260.034	593.498 mg Standard Error 375.124
Analgesics Used Post Discharge (Acetylsalicylic Acid [Week 2] and Paracetamol [Weeks 2, 4, and 6] Paracetamol, Week 6/ET (n=6, 14, 5)	1128.952 mg Standard Error 290.993	1098.840 mg Standard Error 223.948	1385.873 mg Standard Error 334.859

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 6/ET

Population: MITT. There were not enough subjects with data at Week 2 and Week 4 for Ibuprofen to calculate least squares mean values.

Weeks 2, 4, and 6 total daily doses were calculated by adding the cumulative doses during the 2 week period prior to the visit and dividing them by the number of days in the period.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=3 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=1 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Analgesics Used Post Discharge (Ibuprofen) for the Pregabalin 150 mg and Placebo Treatment Groups	862.350 mg Standard Error 584.827	983.850 mg Standard Error 1119.858	—

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 6/ET

Population: MITT. There were not enough subjects with data at Week 2 for Ibuprofen to calculate least squares mean values.

Weeks 2, 4, and 6 total daily doses were calculated by adding the cumulative doses during the 2 week period prior to the visit and dividing them by the number of days in the period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 4

Population: MITT

Week 4 total daily dose was calculated by adding the cumulative doses during the 2 week period prior to the visit and dividing them by the number of days in the period.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=5 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=1 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Analgesics Used Post Discharge (Acetylsalicylic Acid) for the Pregabalin 150 mg and Placebo Treatment Groups at Week 4	650.000 mg Full Range 0.000 • Interval 81.0 to 1300.0	22.100 mg Interval 22.1 to 22.1	—

SECONDARY outcome

Population: MITT

NPSI: subject rated questionnaire to evaluate 5 dimensions of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia). Includes 10 descriptors ranging from 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each relevant dimension. Total score is calculated as the sum of scores of the 10 descriptors, range: 0-100. Higher score indicates greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin (150 mg) n=23 Participants Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=24 Participants Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=29 Participants Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Neuropathic Pain Symptom Inventory (NPSI) Burning Spontaneous Pain, Month 6, (n=22, 15, 15)	1.091 scores on a scale Standard Deviation 2.114	1.400 scores on a scale Standard Deviation 2.324	0.667 scores on a scale Standard Deviation 1.113
Neuropathic Pain Symptom Inventory (NPSI) Burning Spontaneous Pain, Month 3, (n=23, 24, 29)	1.348 scores on a scale Standard Deviation 2.479	0.792 scores on a scale Standard Deviation 2.085	0.828 scores on a scale Standard Deviation 1.947
Neuropathic Pain Symptom Inventory (NPSI) Pressing Spontaneous Pain, Month 3, (n=23, 24, 29)	1.457 scores on a scale Standard Deviation 2.083	0.958 scores on a scale Standard Deviation 1.574	0.948 scores on a scale Standard Deviation 1.496
Neuropathic Pain Symptom Inventory (NPSI) Pressing Spontaneous Pain, Month 6, (n=22, 15, 15)	1.409 scores on a scale Standard Deviation 2.158	1.333 scores on a scale Standard Deviation 1.655	0.633 scores on a scale Standard Deviation 1.445
Neuropathic Pain Symptom Inventory (NPSI) Paroxysmal Pain, Month 3, (n=23, 24, 29)	0.804 scores on a scale Standard Deviation 1.042	1.688 scores on a scale Standard Deviation 2.417	1.086 scores on a scale Standard Deviation 1.909
Neuropathic Pain Symptom Inventory (NPSI) Paroxysmal Pain, Month 6, (n=22, 15, 15)	1.205 scores on a scale Standard Deviation 2.711	1.133 scores on a scale Standard Deviation 2.175	0.533 scores on a scale Standard Deviation 1.246
Neuropathic Pain Symptom Inventory (NPSI) Evoked Pain, Month 3, (n=23, 24, 29)	1.174 scores on a scale Standard Deviation 1.700	1.319 scores on a scale Standard Deviation 2.004	0.931 scores on a scale Standard Deviation 1.344
Neuropathic Pain Symptom Inventory (NPSI) Evoked Pain, Month 6, (n=22, 15, 15)	0.636 scores on a scale Standard Deviation 0.937	1.667 scores on a scale Standard Deviation 2.402	0.711 scores on a scale Standard Deviation 1.298
Neuropathic Pain Symptom Inventory (NPSI) Paresthesia/Dysesthesia, Month 3, (n=23, 24, 29)	0.848 scores on a scale Standard Deviation 1.473	0.604 scores on a scale Standard Deviation 1.406	0.690 scores on a scale Standard Deviation 1.160
Neuropathic Pain Symptom Inventory (NPSI) Paresthesia/Dysesthesia, Month 6, (n=22, 15, 15)	0.773 scores on a scale Standard Deviation 1.674	0.500 scores on a scale Standard Deviation 1.086	0.033 scores on a scale Standard Deviation 0.129
Neuropathic Pain Symptom Inventory (NPSI) Total Score, Month 3, (n=23, 24, 29)	0.058 scores on a scale Standard Deviation 0.061	0.055 scores on a scale Standard Deviation 0.075	0.045 scores on a scale Standard Deviation 0.059
Neuropathic Pain Symptom Inventory (NPSI) Total Score, Month 6, (n=22, 15, 15)	0.051 scores on a scale Standard Deviation 0.074	0.061 scores on a scale Standard Deviation 0.078	0.027 scores on a scale Standard Deviation 0.036

Adverse Events

Pregabalin (150 mg)

Serious events: 11 serious events

Other events: 76 other events

Deaths: 0 deaths

Pregabalin (300 mg)

Serious events: 11 serious events

Other events: 76 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin (150 mg) n=98 participants at risk Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=96 participants at risk Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=98 participants at risk Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Cardiac disorders Cardiac failure congestive	0.00% 0/98	1.0% 1/96	0.00% 0/98
General disorders Chest pain	0.00% 0/98	0.00% 0/96	1.0% 1/98
General disorders Oedema peripheral	1.0% 1/98	0.00% 0/96	0.00% 0/98
General disorders Pyrexia	1.0% 1/98	0.00% 0/96	0.00% 0/98
Hepatobiliary disorders Porcelain gallbladder	0.00% 0/98	1.0% 1/96	0.00% 0/98
Immune system disorders Anaphylactic reaction	0.00% 0/98	1.0% 1/96	0.00% 0/98
Infections and infestations Cellulitis	1.0% 1/98	0.00% 0/96	0.00% 0/98
Infections and infestations Urinary tract infection	0.00% 0/98	0.00% 0/96	1.0% 1/98
Injury, poisoning and procedural complications Device dislocation	1.0% 1/98	0.00% 0/96	0.00% 0/98
Injury, poisoning and procedural complications Fall	2.0% 2/98	0.00% 0/96	0.00% 0/98
Injury, poisoning and procedural complications Joint injury	1.0% 1/98	0.00% 0/96	0.00% 0/98
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/98	0.00% 0/96	1.0% 1/98
Investigations Bacterial culture positive	0.00% 0/98	0.00% 0/96	1.0% 1/98
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 1/98	0.00% 0/96	0.00% 0/98
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/98	1.0% 1/96	0.00% 0/98
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.0% 1/98	1.0% 1/96	0.00% 0/98
Nervous system disorders Cerebrovascular accident	1.0% 1/98	0.00% 0/96	0.00% 0/98
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/98	0.00% 0/96	1.0% 1/98
Psychiatric disorders Depression	0.00% 0/98	1.0% 1/96	0.00% 0/98
Renal and urinary disorders Renal failure acute	0.00% 0/98	0.00% 0/96	1.0% 1/98
Renal and urinary disorders Urinary retention	1.0% 1/98	0.00% 0/96	0.00% 0/98
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/98	3.1% 3/96	0.00% 0/98
Respiratory, thoracic and mediastinal disorders Respiratory depression	0.00% 0/98	0.00% 0/96	1.0% 1/98
Surgical and medical procedures Muscle flap operation	0.00% 0/98	0.00% 0/96	1.0% 1/98
Vascular disorders Deep vein thrombosis	0.00% 0/98	2.1% 2/96	0.00% 0/98
Vascular disorders Haematoma	1.0% 1/98	0.00% 0/96	1.0% 1/98
Vascular disorders Hypotension	1.0% 1/98	1.0% 1/96	0.00% 0/98
Vascular disorders Thrombosed varicose vein	1.0% 1/98	0.00% 0/96	0.00% 0/98
Vascular disorders Thrombosis	1.0% 1/98	0.00% 0/96	0.00% 0/98

Other adverse events

Other adverse events
Measure	Pregabalin (150 mg) n=98 participants at risk Pregabalin capsules orally 75 mg the evening before surgery (approximately 12 hours prior to surgery) followed by 75 mg approximately 2 hours before surgery followed by 150 mg/day (75 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Pregabalin (300 mg) n=96 participants at risk Pregabalin capsules orally 150 mg the night before surgery (approximately 12 hours prior to surgery) followed by 150 mg approximately 2 hours before surgery followed by 300 mg/day (150 mg twice daily) for up to 6 post-operative weeks starting on POD 1.	Placebo n=98 participants at risk Matching Placebo capsules orally: 1 dose the evening before surgery (approximately 12 hours prior to surgery), 1 dose approximately 2 hours before surgery followed by twice daily dosing for up to 6 post-operative weeks starting on POD 1.
Psychiatric disorders Anxiety	2.0% 2/98	4.2% 4/96	6.1% 6/98
Psychiatric disorders Confusional state	9.2% 9/98	10.4% 10/96	5.1% 5/98
Psychiatric disorders Insomnia	8.2% 8/98	12.5% 12/96	17.3% 17/98
Renal and urinary disorders Dysuria	5.1% 5/98	4.2% 4/96	5.1% 5/98
Skin and subcutaneous tissue disorders Pruritus	15.3% 15/98	12.5% 12/96	21.4% 21/98
Vascular disorders Hypertension	4.1% 4/98	3.1% 3/96	7.1% 7/98
Vascular disorders Hypotension	12.2% 12/98	11.5% 11/96	5.1% 5/98
Blood and lymphatic system disorders Anaemia	6.1% 6/98	3.1% 3/96	9.2% 9/98
Blood and lymphatic system disorders Haemorrhagic anaemia	4.1% 4/98	3.1% 3/96	4.1% 4/98
Eye disorders Vision blurred	0.00% 0/98	7.3% 7/96	0.00% 0/98
Gastrointestinal disorders Constipation	24.5% 24/98	12.5% 12/96	30.6% 30/98
Gastrointestinal disorders Diarrhoea	1.0% 1/98	4.2% 4/96	3.1% 3/98
Gastrointestinal disorders Dry mouth	2.0% 2/98	4.2% 4/96	1.0% 1/98
Gastrointestinal disorders Dyspepsia	2.0% 2/98	3.1% 3/96	5.1% 5/98
Gastrointestinal disorders Nausea	29.6% 29/98	32.3% 31/96	52.0% 51/98
Gastrointestinal disorders Vomiting	14.3% 14/98	15.6% 15/96	25.5% 25/98
General disorders Fatigue	20.4% 20/98	15.6% 15/96	19.4% 19/98
General disorders Oedema	1.0% 1/98	4.2% 4/96	2.0% 2/98
General disorders Oedema peripheral	7.1% 7/98	9.4% 9/96	11.2% 11/98
General disorders Pyrexia	13.3% 13/98	16.7% 16/96	5.1% 5/98
Infections and infestations Urinary tract infection	4.1% 4/98	2.1% 2/96	4.1% 4/98
Injury, poisoning and procedural complications Anaemia postoperative	7.1% 7/98	7.3% 7/96	3.1% 3/98
Injury, poisoning and procedural complications Postoperative fever	2.0% 2/98	3.1% 3/96	4.1% 4/98
Injury, poisoning and procedural complications Procedural nausea	5.1% 5/98	2.1% 2/96	1.0% 1/98
Injury, poisoning and procedural complications Procedural pain	6.1% 6/98	7.3% 7/96	5.1% 5/98
Investigations Body temperature increased	4.1% 4/98	5.2% 5/96	1.0% 1/98
Investigations Haematocrit decreased	5.1% 5/98	4.2% 4/96	3.1% 3/98
Investigations Haemoglobin decreased	6.1% 6/98	5.2% 5/96	3.1% 3/98
Metabolism and nutrition disorders Hypokalaemia	1.0% 1/98	3.1% 3/96	5.1% 5/98
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/98	2.1% 2/96	4.1% 4/98
Musculoskeletal and connective tissue disorders Back pain	6.1% 6/98	2.1% 2/96	1.0% 1/98
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/98	3.1% 3/96	4.1% 4/98
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/98	4.2% 4/96	0.00% 0/98
Musculoskeletal and connective tissue disorders Pain in extremity	7.1% 7/98	2.1% 2/96	6.1% 6/98
Nervous system disorders Disturbance in attention	10.2% 10/98	11.5% 11/96	11.2% 11/98
Nervous system disorders Dizziness	20.4% 20/98	26.0% 25/96	16.3% 16/98
Nervous system disorders Headache	7.1% 7/98	3.1% 3/96	9.2% 9/98
Nervous system disorders Hypoaesthesia	3.1% 3/98	4.2% 4/96	2.0% 2/98
Nervous system disorders Somnolence	24.5% 24/98	22.9% 22/96	20.4% 20/98

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER