Trial Outcomes & Findings for Effect of Oral Pregabalin on Spinal Neurotransmitters in Patients Undergoing Knee Replacement (NCT NCT00729690)

Results Overview

Numerical Response scale NRS(0-10) Pain scores were collected every 4 hours after the initial dose and the Area Under the Curve (AUC) calculated. Calculated for the 1st 24 hours after initial dose (0-24hr). AUC measured in NRS pain score points per hour (NRS\*hr). Larger AUC values indicate higher levels of reported pain.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

48 participants

Primary outcome timeframe

24 hours

Results posted on

2012-12-19

Participant Flow

Forty-eight patients scheduled to undergo elective primary Total Knee Replacement (TKR) for osteoarthritis by 2 orthopedic surgeons were recruited at the Rush University Medical Center (Chicago, Illinois).

Participant milestones

Participant milestones
Measure	1 Multi-Dose Pregabalin Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
Overall Study STARTED	16	16	16
Overall Study COMPLETED	16	14	14
Overall Study NOT COMPLETED	0	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	1 Multi-Dose Pregabalin Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
Overall Study IT Catheter Malfunction	0	2	2

Baseline Characteristics

Effect of Oral Pregabalin on Spinal Neurotransmitters in Patients Undergoing Knee Replacement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Multi-Dose Pregabalin n=16 Participants Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=16 Participants Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=16 Participants Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)	Total n=48 Participants Total of all reporting groups
Age Continuous	66.9 years STANDARD_DEVIATION 6.4 • n=5 Participants	64.8 years STANDARD_DEVIATION 4.4 • n=7 Participants	66.4 years STANDARD_DEVIATION 4.5 • n=5 Participants	66.1 years STANDARD_DEVIATION 5.2 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants
Region of Enrollment United States	16 participants n=5 Participants	16 participants n=7 Participants	16 participants n=5 Participants	48 participants n=4 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: All Completed Patients were included in the analysis.

Numerical Response scale NRS(0-10) Pain scores were collected every 4 hours after the initial dose and the Area Under the Curve (AUC) calculated. Calculated for the 1st 24 hours after initial dose (0-24hr). AUC measured in NRS pain score points per hour (NRS\*hr). Larger AUC values indicate higher levels of reported pain.

Outcome measures

Outcome measures
Measure	1 Multi-Dose Pregabalin n=16 Participants Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=14 Participants Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=14 Participants Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
NRS Pain Score AUC (NRS*hr) - 1st 24 Hours	70.4 Area (NRS*hr) Standard Deviation 34.4	59.6 Area (NRS*hr) Standard Deviation 31.1	73.4 Area (NRS*hr) Standard Deviation 34.6

PRIMARY outcome

Timeframe: 12 hours Post dose

Population: All Completed Patients

Numerical Response scale NRS(0-10) Pain scores were collected every 4 hours after the initial dose and the Area Under the Curve (AUC) calculated. Calculated for the 1st 12 hours after initial dose (0-12hr). AUC measured in NRS pain score points per hour (NRS\*hr). Larger AUC values indicate higher levels of reported pain.

Outcome measures

Outcome measures
Measure	1 Multi-Dose Pregabalin n=16 Participants Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=14 Participants Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=14 Participants Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
NRS Pain Score AUC (NRS*hr) - 1st 12 Hours	30.1 Area (NRS*hr) Standard Deviation 15.6	22.7 Area (NRS*hr) Standard Deviation 16.9	27.7 Area (NRS*hr) Standard Deviation 16.7

SECONDARY outcome

Timeframe: PostOp day 2

Population: All completed patients used.

The degree of active knee flexion (ROM) tolerated by the patient will be assessed at days 1 and 2 post-surgery. Active flexion is the unassisted moment of the joint by the subject. On postoperative (PostOp) day 2

Outcome measures

Outcome measures
Measure	1 Multi-Dose Pregabalin n=16 Participants Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=14 Participants Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=14 Participants Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
Active Knee Flexion	78.1 Degrees Standard Deviation 10.6	80.5 Degrees Standard Deviation 10.1	80.5 Degrees Standard Deviation 7.0

SECONDARY outcome

Timeframe: PostOp day 2

Population: All Completed Patients were used

Passive flexion is the moment of the joint with the assistance of a clinician (The clinician or therapist physically hold and moves the knee through it's range of motion).

Outcome measures

Outcome measures
Measure	1 Multi-Dose Pregabalin n=16 Participants Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=14 Participants Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=14 Participants Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
Passive Knee Flexion	86.5 Degrees Standard Deviation 15.3	88.2 Degrees Standard Deviation 9.44	87.1 Degrees Standard Deviation 10.6

Adverse Events

1 Multi-Dose Pregabalin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

2 Single-dose Pregabalin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

3 Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	1 Multi-Dose Pregabalin n=16 participants at risk Multi-dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery and then repeat 150 mg doses at 12 and 24 hours after initial dose.	2 Single-dose Pregabalin n=16 participants at risk Single dose pregabalin: patients receive pregabalin 150 mg orally 1 hour prior to surgery, and then placebo doses at 12 and 24 hours after initial dose.	3 Placebo n=16 participants at risk Placebo: patients receive matching placebo at the same 3 time points as Groups 1 and 2 (orally 1 hour prior to surgery and then repeat doses at 12 and 24 hours after initial dose.)
Skin and subcutaneous tissue disorders Pruritus	12.5% 2/16 • Number of events 2	18.8% 3/16 • Number of events 3	43.8% 7/16 • Number of events 7

Additional Information

Asokumar Buvanendran

Rush University

Phone: (312) 942-3685

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place