CompletedNCT01333956Updated May 18, 2016Results posted

Effects of Pregabalin on Pain After Total Knee Arthroplasty

A Phase 1/2 interventional study of Pregabalin 50mg and Pregabalin 100mg in Primary Total Knee Arthroplasty, sponsored by Hospital for Special Surgery, New York. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2016-05-18.

Sponsored by Hospital for Special Surgery, New York · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 120
Allocation: Randomized
Ages: 18 Years to 80 Years
Sex: All

Study summary

Total knee arthroplasty can cause severe postoperative pain, and patients typically receive oral opioid analgesics for over 2 weeks. Side effects of pain management may impair participation in physical therapy and diminish patient satisfaction. Anecdotally, it seems that pregabalin is very helpful to patients after total knee arthroplasty. However, pregabalin can have side effects. It is not clear how much pregabalin to prescribe. Low doses may not be effective, but use of high doses may increase the incidence and severity of side effects.The purpose of this study is to determine which dosage of pregabalin is the most effective at reducing pain after knee surgery.

Conditions studied

Primary Total Knee Arthroplasty

In context

Lead sponsor

Hospital for Special Surgery, New York is the lead sponsor of 226 studies on the registry; 40 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 22 (73%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Patients with osteoarthritis scheduled for primary tricompartmental total knee arthroplasty with a participating surgeon
Age 18 to 80 years old
Planned use of regional anesthesia
Ability to follow study protocol
English speaking (primary outcome obtained via telephone call and secondary outcomes include questionnaires validated in English only)
Patients planning on being discharged home or to a rehabilitation center that has agreed to participate

Exclusion criteria

Exclusion Criteria:

Patients younger than 18 years old and older than 80
Patients intending to receive general anesthesia
Allergy or intolerance to one of the study medications
Patients with an ASA of IV
Patients with hepatic (liver) failure
Patients with chronic renal (kidney) failure (Defined as estimated creatinine clearance \< 30 mL/min, based on recommendation that total daily pregabalin dose be reduced to 150 mg with Clcr \< 30 mL/min, CLcr=[(140-age (years)] x weight (kg)x0.85 (for female patients)/[72xserum creatinine (mg/dL)])
Patients with difficult to manage diabetes mellitus, including insulin-dependence
Chronic gabapentin/pregabalin use (regular use for longer than 3 months)
Chronic opioid use (taking opioids for longer than 3 months)
Patients with major prior ipsilateral open knee surgery.
Chronic neurontin/lyrica use

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 120 participants (actual)

Study arms

Placebo comparator
Control
Patients will receive 0mg of pregabalin
Drug: Placebo
Experimental
50mg Arm
Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of post-operative day (POD)14 and one capsule at bedtime POD15, POD16.
Drug: Pregabalin 50mg
Experimental
100mg Arm
Patients will receive 100mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Drug: Pregabalin 100mg
Experimental
150mg Arm
Patients will receive 150mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Drug: Pregabalin 150mg

Interventions

DrugPregabalin 50mg
Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Also known as: Lyrica
DrugPregabalin 100mg
Patients will receive 100mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Also known as: Lyrica
DrugPregabalin 150mg
Patients will receive 150mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Also known as: Lyrica
DrugPlacebo
Patients will receive placebo drug with no active ingredients per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.

What researchers measure

Primary outcomes

Postoperative Pain
Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable).
Time frame: 2 weeks postoperatively

Secondary outcomes

Opioid-Related Symptom Distress Score
Opioid-Related Symptom Distress score (ORSDS) measured at POD1 and POD14. The ORSDS is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. (0=low; 4=high).
Time frame: 2 weeks postoperatively
Self-assessed Sedation and Confusion
Self-assessed sedation and confusion (POD1). Confusion Assessment Method (CAM score) (pre-operative and on POD1)
Time frame: 1 day postoperatively
Numeric Rating Scale (NRS)
NRS Pain (pre-operative, POD1, POD3, 2 weeks, 3 months, at orthopedic visits). Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months)
Time frame: 3 months
Neuropathic Pain
Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months). Scale of 0 to 24. Higher values represent worse outcomes.
Time frame: 3 months
Opioid Usage
Opioid Usage (POD1, POD 3, 2 weeks, 3 months)
Time frame: 3 months
Satisfaction
Satisfaction with pain management (1-10 scale; 1 = very dissatisfied, 10 = very satisfied)
Time frame: 2 weeks

Results

Posted May 18, 2016

Participant flow

Participant flow — Overall Study
Milestone	Control	50mg Arm	100mg Arm	150mg Arm
Started	30	30	30	30
Completed	28	26	29	28
Not completed	2	4	1	2
Withdrew: Lost to follow-up	1	2	0	1
Withdrew: Unable to complete study procedure	1	0	0	1
Withdrew: Withdrawal by subject	0	2	1	0

Outcome measures

PrimaryPostoperative Pain

Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable).

Time frame:: 2 weeks postoperatively
Reported as:: Mean · units on a scale

Postoperative Pain
units on a scale	Control	50mg Arm	100mg Arm	150mg Arm
POD14 Pain score with flexion	4 ± 2.3	4.8 ± 2.1	4.5 ± 2.4	4.0 ± 2.1
POD14 Pain score with ambulation	3.6 ± 2.0	3.8 ± 1.6	3.5 ± 1.8	3.1 ± 1.9
POD14 Pain score at rest	2.9 ± 2.3	2.9 ± 2.0	2.8 ± 1.8	2.7 ± 2.1

SecondaryOpioid-Related Symptom Distress Score

Opioid-Related Symptom Distress score (ORSDS) measured at POD1 and POD14. The ORSDS is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. (0=low; 4=high).

Time frame:: 2 weeks postoperatively
Reported as:: Median · units on a scale

Opioid-Related Symptom Distress Score
units on a scale	Control	50mg Arm	100mg Arm	150mg Arm
ORSDS POD1	.4 (.2 to .7)	.4 (.2 to .6)	.5 (.2 to .7)	.4 (.2 to .8)
ORSDS POD14	.3 (.1 to .5)	.3 (.1 to .5)	.3 (.1 to .5)	.3 (0 to .4)

SecondarySelf-assessed Sedation and Confusion

Self-assessed sedation and confusion (POD1). Confusion Assessment Method (CAM score) (pre-operative and on POD1)

Time frame:: 1 day postoperatively
Reported as:: Number · percentage of patients

Self-assessed Sedation and Confusion
percentage of patients	Control	50mg Arm	100mg Arm	150mg Arm
Drowsiness POD1 [ORSDS]	34.5	37.9	55.2	58.6
Nausea POD1 [ORSDS]	34.5	41.4	44.8	31.0

SecondaryNumeric Rating Scale (NRS)

NRS Pain (pre-operative, POD1, POD3, 2 weeks, 3 months, at orthopedic visits). Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months)

Time frame:: 3 months
Reported as:: Mean · units on a scale

Numeric Rating Scale (NRS)
units on a scale	Control	50mg Arm	100mg Arm	150mg Arm
Preop NRS Pain Score with Flexion	4.9 (3.7 to 6)	5.4 (4.3 to 6.5)	3.9 (2.8 to 5.1)	5.7 (4.4 to 7)
POD1 NRS Pain Score with Flexion	2.8 (1.8 to 4)	2.9 (2 to 4)	2.7 (1.8 to 3.3)	2.5 (1.2 to 3.3)
POD3 NRS Pain Score with Flexion	3.9 (2.8 to 4.8)	4.2 (3.5 to 5.2)	3.6 (2.8 to 4.7)	4.3 (3.3 to 5.3)
POD14 NRS Pain Score with Flexion	4 (3.4 to 5)	4.9 (4.2 to 5.6)	4.5 (3.7 to 5.4)	4.2 (3.2 to 5)
3 months NRS Pain Score with Flexion	2 (1 to 3)	1.9 (.9 to 2.7)	1.7 (.7 to 1.8)	1.8 (.9 to 2.3)

SecondaryNeuropathic Pain

Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months). Scale of 0 to 24. Higher values represent worse outcomes.

Time frame:: 3 months
Reported as:: Median · units on a scale

Neuropathic Pain
units on a scale	Control	50mg Arm	100mg Arm	150mg Arm
Neuropathic Pain	0 (0 to 3)	0 (0 to 6)	0 (0 to 0)	0 (0 to 3)

SecondaryOpioid Usage

Opioid Usage (POD1, POD 3, 2 weeks, 3 months)

Time frame:: 3 months
Reported as:: Mean · mg

Opioid Usage
mg	Control	50mg Arm	100mg Arm	150mg Arm
Preop Total Opioid Use (mg)	19 (16 to 22)	18 (16 to 20)	17 (15 to 19)	18 (16 to 20)
POD 1 Total Opioid Use (mg)	50 (40 to 63)	46 (35 to 57)	57 (41 to 73)	45 (35 to 55)
POD 2 Total Opioid Use (mg)	70 (57 to 85)	60 (50 to 70)	63 (47 to 79)	55 (43 to 65)
POD 3 Total Opioid Use (mg)	55 (43 to 67)	60 (50 to 70)	40 (30 to 50)	36 (30 to 42)
POD 14 Total Opioid Use (mg)	40 (30 to 50)	36 (25 to 45)	40 (30 to 50)	45 (25 to 55)
3 months Total Opioid Use (mg)	0 (0 to 2)	3 (0 to 5)	0 (0 to 1)	4 (0 to 6)

SecondarySatisfaction

Satisfaction with pain management (1-10 scale; 1 = very dissatisfied, 10 = very satisfied)

Time frame:: 2 weeks
Reported as:: Median · units on a scale

Satisfaction
units on a scale	Control	50mg Arm	100mg Arm	150mg Arm
Satisfaction	9 (8 to 10)	8 (7 to 10)	8 (5 to 9)	8 (6 to 9.3)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Control	—	0/30 (0%)	0/30 (0%)
50mg Arm	—	0/30 (0%)	0/30 (0%)
100mg Arm	—	0/30 (0%)	0/30 (0%)
150mg Arm	—	0/30 (0%)	0/30 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Control	50mg Arm	100mg Arm	150mg Arm	Total
Mean	65.5 ± 9.8	66.8 ± 6.3	65.1 ± 7.1	67.7 ± 8.1	66.3 ± 7.9

Sex: Female, Male
Sex: Female, Male(Participants)	Control	50mg Arm	100mg Arm	150mg Arm	Total
Female	14	18	13	23	68
Male	16	12	17	7	52

Region of Enrollment
Region of Enrollment(participants)	Control	50mg Arm	100mg Arm	150mg Arm	Total
United States	30	30	30	30	120

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m ^ 2)	Control	50mg Arm	100mg Arm	150mg Arm	Total
Mean	32 ± 5	32 ± 6	32 ± 6	30 ± 7	31.5 ± 2.45

Study locations

1 site

Hospital for Special Surgery
New York, New York 10021, United States

References and documents

Publications

YaDeau JT, Lin Y, Mayman DJ, Goytizolo EA, Alexiades MM, Padgett DE, Kahn RL, Jules-Elysee KM, Ranawat AS, Bhagat DD, Fields KG, Goon AK, Curren J, Westrich GH. Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial. Br J Anaesth. 2015 Aug;115(2):285-93. doi: 10.1093/bja/aev217. PubMed 26170351 ↗

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of May 2011, a primary completion of Mar 2013 and a completion of Jun 2013. It does not say whether these dates are actual or estimated.

Results were first posted in May 2016, 3 years 2 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Apr 8, 2011
First posted: Apr 12, 2011
Start: May 2011
Primary completionActual: Mar 2013
CompletionActual: Jun 2013
Results first posted: May 18, 2016
Last update: May 18, 2016

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on May 18, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01333956
Lead sponsor: Hospital for Special Surgery, New York
Responsible party: Sponsor
First posted: Apr 12, 2011
Start date: May 2011
Primary completion: Mar 2013
Completion: Jun 2013
Results posted: May 18, 2016
Last update: May 18, 2016

Study contacts

Jacques T YaDeau, M.D., Ph.D.

principal investigator · Hospital for Special Surgery, New York

View the source record on ClinicalTrials.gov ↗

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