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Phase 3 N=307 Randomized Double-blind Treatment

Efficacy And Safety Of Pregabalin For Pain Following Total Knee Replacement

Osteoarthritis · Postoperative Pain

Enrolled (actual)
307
Serious AEs
9.3%
Results posted
Aug 2010
Primary outcome: Primary: 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; 6.740; 7.079 scores on a scale — p=0.9185

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
pregabalin (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Primary completion
Dec 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
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; 6.740; 7.079 0.9185
SECONDARY
Cumulative Total Amount of Opioids Used During the Entire Hospital Stay
151.790; 152.306; 167.854; 86.402; 93.846; 122.830 0.4091
SECONDARY
Opioids Used Post Discharge
30.255; 27.692; 26.119; 37.130; 37.507; 34.271 0.3602
SECONDARY
Analgesics Used During the Hospital Stay (Acetylsalicylic Acid, Ketorolac, and Paracetamol)
235.175; 1442.025; 1425.825; 32.961; 53.432; 27.189 0.0656
SECONDARY
Analgesics Used Post Discharge (Acetylsalicylic Acid [Week 2] and Paracetamol [Weeks 2, 4, and 6]
498.613; 797.463; 992.613; 603.496; 665.574; 630.787 0.1996
SECONDARY
Analgesics Used Post Discharge (Ibuprofen) for the Pregabalin 150 mg and Placebo Treatment Groups
862.350; 983.850 0.9341
SECONDARY
Analgesics Used Post Discharge (Ibuprofen) for the Pregabalin 300 mg Treatment Group
SECONDARY
Analgesics Used Post Discharge (Acetylsalicylic Acid) for the Pregabalin 150 mg and Placebo Treatment Groups at Week 4
650.000; 22.100 <0.0001 sig
SECONDARY
Analgesics Used Post Discharge (Acetylsalicylic Acid) for the Pregabalin 300 mg Treatment Group at Week 4
SECONDARY
Analgesics Used Post Discharge (Acetylsalicylic Acid) for the Pregabalin 150 mg and Placebo Treatment Groups at Week 6/ET
513.163
SECONDARY
Analgesics Used Post Discharge (Acetylsalicylic Acid) for the Pregabalin 300 mg and Placebo Treatment Groups at Week 6/ET
SECONDARY
The Effect of Pregabalin Compared to Placebo on the Occurrence of Opioid-Related Symptoms as Assessed Using the Opioid-Related Symptom Distress Scale (OR-SDS) - Frequency Composite Score
0.767; 0.808; 0.888; 0.782; 0.779; 0.908 0.1661
SECONDARY
The Effect of Pregabalin Compared to Placebo on the Occurrence of Opioid-Related Symptoms as Assessed Using the OR-SDS - Severity Composite Score
0.579; 0.590; 0.621; 0.642; 0.624; 0.695 0.5791
SECONDARY
The Effect of Pregabalin Compared to Placebo on the Occurrence of Opioid-Related Symptoms as Assessed Using the OR-SDS - Degree of Bother Composite Score
0.671; 0.788; 0.836; 0.810; 0.769; 0.918 0.1078
SECONDARY
The Effect of Pregabalin Compared to Placebo on the Occurrence of Opioid-Related Symptoms as Assessed Using the OR-SDS - Overall Composite Score
0.669; 0.727; 0.778; 0.743; 0.722; 0.838 0.1949
SECONDARY
Total Clinically Meaningful Event (CME) Score
0.822; 0.817; 0.772; 0.814; 0.834; 0.789 0.8071
SECONDARY
Pain Interference Index Score as Measured by the m-BPI-sf
3.427; 3.488; 3.887; 2.969; 2.814; 3.037 0.1537
SECONDARY
Pain Interference With Relations With People as Measured by the m-BPI-sf
1.837; 1.716; 2.624; 1.566; 1.370; 1.671 0.0359 sig
SECONDARY
Pain Interference With Enjoyment of Life as Measured by the m-BPI-sf
3.487; 3.769; 3.744; 2.945; 2.802; 2.953 0.5786
SECONDARY
Pain Interference With General Activity as Measured by the m-BPI-sf
3.794; 4.499; 4.764; 3.254; 3.526; 3.524 0.0284 sig
SECONDARY
Pain Interference With Mood as Measured by the m-BPI-sf
2.588; 2.418; 3.354; 2.640; 2.115; 2.554 0.0613
SECONDARY
Pain Interference With Walking Ability as Measured by the m-BPI-sf
4.918; 4.728; 4.982; 3.297; 3.344; 3.425 0.8868
SECONDARY
Pain Interference With Normal Work as Measured by the m-BPI-sf
4.879; 4.738; 4.873; 4.010; 3.539; 3.831 0.9912
SECONDARY
Pain Interference With Sleep as Measured by the m-BPI-sf
2.696; 2.642; 3.307; 3.139; 3.015; 3.587 0.1448
SECONDARY
Daily and Weekly Worst Pain During the Hospital Stay and Post Discharge Assessed by the Pain Numerical Rating Scale (NRS)
7.217; 7.002; 8.770; 7.477; 7.290; 7.201 0.0476 sig
SECONDARY
Daily and Weekly Average Pain During the Hospital Stay and Post Discharge Assessed by the Pain NRS
5.712; 4.845; 6.748; 4.961; 4.614; 4.918 0.1486
SECONDARY
Current Pain During the Hospital Stay Assessed by the Pain NRS
4.940; 3.554; 4.363; 5.083; 4.529; 5.119 0.2211
SECONDARY
Pain-Related Sleep Interference Post Surgery
4.452; 3.671; 5.481; 3.830; 3.408; 4.027 0.0388 sig
SECONDARY
Change From Baseline in Visual Analogue Scale for Anxiety (VAS-Anxiety) Score Prior to Surgery
6.133; 7.103; 6.992; 6.974; 3.272; 6.085 0.7958
SECONDARY
Timed Up-and-Go (TUG)
76.153; 79.973; 82.964; 80.027; 79.548; 86.842 0.5736
SECONDARY
Range of Motion (ROM) Assessment of the Active Flexion of the Surgical Knee
54.877; 60.744; 55.738; 69.981; 73.370; 69.178 0.7742
SECONDARY
ROM Assessment of the Passive Flexion of the Surgical Knee
66.720; 71.523; 64.991; 77.714; 81.322; 76.813 0.5117
SECONDARY
Time From End of Surgery to Meet Hospital Discharge Criteria
106.802; 112.966; 95.531 0.4365
SECONDARY
Time From End of Surgery to Actual Discharge
75.709; 73.906; 78.451 0.4024
SECONDARY
Satisfaction With Current Pain Medication Measured by the Pain Treatment Satisfaction Scale (PTSS)
79.897; 80.706; 77.550; 85.274; 85.294; 80.148 0.3483
SECONDARY
Satisfaction With Medication Characteristics Measured by the PTSS
85.733; 85.732; 81.556; 91.880; 87.869; 84.583 0.0739
SECONDARY
Satisfaction With Medication Efficacy Measured by the PTSS
74.156; 75.705; 73.577; 78.669; 82.724; 75.713 0.8545
SECONDARY
Overall Satisfaction Measured by the PTSS
1.845; 1.654; 1.821; 2.333; 1.667; 1.833 0.9405
SECONDARY
Overall Pain Relief Measured by the PTSS
2.260; 1.696; 2.051; 2.333; 1.667; 1.833 0.5299
SECONDARY
Number of Subjects With Global Evaluation of Study Medication Scores
31; 27; 19; 31; 46; 39 0.2473
SECONDARY
Number of Subjects With Persistent Pain Based on 11-Point Verbal Rating Scale (VRS)
22; 22; 27; 43; 37; 34 0.1509
SECONDARY
Neuropathic Pain Symptom Inventory (NPSI)
1.348; 0.792; 0.828; 1.091; 1.400; 0.667

Summary

Pregabalin added to the standard of care with dosing starting preoperatively and continuing for up to 6 weeks post surgery will decrease the intensity of post-operative pain following total knee replacement.

Eligibility Criteria

Inclusion Criteria

  • Subjects with osteoarthritis (OA) undergoing elective TKA under regional anesthesia (neuroaxial with or without peripheral nerve block).
  • Subjects able to demonstrate sufficient psychomotor dexterity and cognitive capacity to use Patient Controlled Analgesia/Patient Controlled Epidural Analgesia if used as part of the standard of care.
  • The subject's preoperative health is graded as American Society of Anesthesiology Class 1 to Class 3

Exclusion Criteria

  • Subjects undergoing revision, unicompartmental, bilateral total knee arthroplasty or subjects with planned second knee total knee arthroplasty at time of present procedure.
  • Subjects with inflammatory arthritides (i.e., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis); Lyme disease.
  • Subjects with fibromyalgia and or other chronic pain syndromes
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00442546). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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