Pain, Perioperative
Conditions
Keywords
perioperative, pregabalin, total hip replacement, post-operative pain
Brief summary
The purpose of this study is the investigate if pregabalin started a day before surgery and continued for 14 days post-operatively can reduce post-operative pain, relieve pre- and post-operative anxiety and sleep disturbances.
Interventions
DRUGPlacebo
Placebo as an adjunct to standard of care
DRUGPregabalin
75 mg BD for 14 days
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient is undergoing a routine (i.e., expected to be uncomplicated) total primary or secondary hip replacement surgery performed under a standardized regimen of spinal anesthesia, and is expected to experience moderate to severe post-surgical pain in the absence of post-operative analgesia
Exclusion criteria
* The patient is undergoing a revision to a previous hip replacement procedure, hip replacement procedure further to a road traffic accident with multiple injuries, or a procedure expected to last longer than 4 hours * The patient has a history of uncontrolled chronic disease or a concurrent clinically significant illness or medical condition, which in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain on Movement Score | Every 12 hours from Day 1 to Day 5 post-surgery | Mean pain on movement score was defined as the mean of the pain on movement score over Days 1 to 5 post-surgery. Pain experienced by participant during passive flexion through 90 degree and passive abduction through 30 degree at operated hip joint was evaluated on a scale of 0 to 10 where, 0= no pain and 10= worst possible pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Sleep Interference Score | Day 1 to Day 5 post-surgery | Mean daily sleep interference score was defined as the mean of daily sleep interference numeric rating scale (NRS) score over Days 1 to 5 post-surgery. Daily Sleep Interference Scale (DSIS): participant rated pain during past 24-hour period on NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication. |
| Mean Anxiety Visual Analogue Scale (A-VAS) | Day 0 to Day 5 post-surgery | Mean anxiety visual analogue scale (VAS) was defined as the mean of VAS score on the day of surgery and over Days 1 to 5 post-surgery. Participants measured their degree of anxiety over past 24 hours on a VAS of 0 to 100, where 0 = not at all anxious to 100 = extremely anxious. |
| Mean Daily Pain Score | Day 1 to Day 7, Day 8 to Day 14 post-surgery | Mean daily pain score was defined as the mean of daily pain score over Days 1 to 7 and Days 8 to 14 post-surgery. Daily Pain Rating Scale (DPRS): participant rated 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. |
| Number of Participants With Rescue Medication Usage | Day 0 to Day 6 post-surgery | Rescue medications were used for participants with moderate or severe resting pain. Fentanyl injection (25 microgram \[mcg\] intravenous bolus to a maximum dose of 3 milliliter/day), paracetamol tablet (15 milligram/kilogram orally to a maximum dose of 45 milligram/kilogram/day) were used as rescue medications. |
| Number of Participants With Neuropathic Pain | Day 90, Day 180 post-surgery | ID Pain questionnaire was used to assess neuropathic pain. 6 items questionnaire, did pain feel like: (1)pins and needles (2)hot/burning (3)numb (4)electrical shocks (5)is pain made worse with touch of clothing or bed sheets (6)is pain limited to your joints. Yes response to questions 1-5 were scored as 1, while a yes response to question 6 was scored as -1. No response were scored as 0. Overall score range -1 to 5.Higher score more indicative of pain with a neuropathic component. Number of participants with score 2 or more (which indicated nerve pain) were reported. |
| Time to Mobilization After Surgery | Day 1 to Day 5 post-surgery | Participant was encouraged each day (from Day 3) to attempt walking depending upon the degree of pain on standing. The first day on which the participant was able to walk for 5 steps was the day of mobilization. Median time to mobilization (in hours) was calculated till the day of mobilization. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days. | 35 |
| Placebo Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days. | 37 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 5 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Pregabalin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.5 | 48.9 years STANDARD_DEVIATION 13.3 | 48.0 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 15 Participants | 20 Participants | 35 Participants |
| Sex: Female, Male Male | 20 Participants | 17 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 35 | 22 / 37 |
| serious Total, serious adverse events | 2 / 35 | 0 / 37 |
Outcome results
Primary
Mean Pain on Movement Score
Mean pain on movement score was defined as the mean of the pain on movement score over Days 1 to 5 post-surgery. Pain experienced by participant during passive flexion through 90 degree and passive abduction through 30 degree at operated hip joint was evaluated on a scale of 0 to 10 where, 0= no pain and 10= worst possible pain.
Time frame: Every 12 hours from Day 1 to Day 5 post-surgery
Population: Modified Intent to Treat (MITT) population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Pain on Movement Score | 4.0 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Pain on Movement Score | 3.9 Units on a scale | Standard Error 0.26 |
Secondary
Mean Anxiety Visual Analogue Scale (A-VAS)
Mean anxiety visual analogue scale (VAS) was defined as the mean of VAS score on the day of surgery and over Days 1 to 5 post-surgery. Participants measured their degree of anxiety over past 24 hours on a VAS of 0 to 100, where 0 = not at all anxious to 100 = extremely anxious.
Time frame: Day 0 to Day 5 post-surgery
Population: MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Anxiety Visual Analogue Scale (A-VAS) | 23.3 Units on a scale | Standard Error 3.33 |
| Placebo | Mean Anxiety Visual Analogue Scale (A-VAS) | 24.7 Units on a scale | Standard Error 2.88 |
Secondary
Mean Daily Pain Score
Mean daily pain score was defined as the mean of daily pain score over Days 1 to 7 and Days 8 to 14 post-surgery. Daily Pain Rating Scale (DPRS): participant rated 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.
Time frame: Day 1 to Day 7, Day 8 to Day 14 post-surgery
Population: MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies participants who were evaluable for this measure at specified time-point for each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Daily Pain Score | Days 1 to 7 (n=27,30) | 2.6 Units on a scale | Standard Error 0.23 |
| Pregabalin | Mean Daily Pain Score | Days 8 to 14 (n=26,27) | 1.8 Units on a scale | Standard Error 0.25 |
| Placebo | Mean Daily Pain Score | Days 1 to 7 (n=27,30) | 2.6 Units on a scale | Standard Error 0.24 |
| Placebo | Mean Daily Pain Score | Days 8 to 14 (n=26,27) | 1.4 Units on a scale | Standard Error 0.25 |
Secondary
Mean Daily Sleep Interference Score
Mean daily sleep interference score was defined as the mean of daily sleep interference numeric rating scale (NRS) score over Days 1 to 5 post-surgery. Daily Sleep Interference Scale (DSIS): participant rated pain during past 24-hour period on NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication.
Time frame: Day 1 to Day 5 post-surgery
Population: MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Daily Sleep Interference Score | 2.6 Units on a scale | Standard Error 0.34 |
| Placebo | Mean Daily Sleep Interference Score | 3.1 Units on a scale | Standard Error 0.29 |
Secondary
Number of Participants With Neuropathic Pain
ID Pain questionnaire was used to assess neuropathic pain. 6 items questionnaire, did pain feel like: (1)pins and needles (2)hot/burning (3)numb (4)electrical shocks (5)is pain made worse with touch of clothing or bed sheets (6)is pain limited to your joints. Yes response to questions 1-5 were scored as 1, while a yes response to question 6 was scored as -1. No response were scored as 0. Overall score range -1 to 5.Higher score more indicative of pain with a neuropathic component. Number of participants with score 2 or more (which indicated nerve pain) were reported.
Time frame: Day 90, Day 180 post-surgery
Population: Data was not analyzed as the intended sample size was not met, and the reported numbers from the final set were not sufficient for a meaningful analysis.
Secondary
Number of Participants With Rescue Medication Usage
Rescue medications were used for participants with moderate or severe resting pain. Fentanyl injection (25 microgram \[mcg\] intravenous bolus to a maximum dose of 3 milliliter/day), paracetamol tablet (15 milligram/kilogram orally to a maximum dose of 45 milligram/kilogram/day) were used as rescue medications.
Time frame: Day 0 to Day 6 post-surgery
Population: MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Number of Participants With Rescue Medication Usage | 17 participants |
| Placebo | Number of Participants With Rescue Medication Usage | 25 participants |
Secondary
Time to Mobilization After Surgery
Participant was encouraged each day (from Day 3) to attempt walking depending upon the degree of pain on standing. The first day on which the participant was able to walk for 5 steps was the day of mobilization. Median time to mobilization (in hours) was calculated till the day of mobilization.
Time frame: Day 1 to Day 5 post-surgery
Population: MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Time to Mobilization After Surgery | 72.500 hours |
| Placebo | Time to Mobilization After Surgery | 52.417 hours |