Reducing Postoperative Side Effect of Pregabalin
Primary Purpose
Pain, Postoperative, Arthroplasty, Replacement, Knee, Arthroplasty, Replacement, Hip
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
37.5mg Pregabalin + 75mg Pregabalin
75mg Pregabalin
Sponsored by

About this trial
This is an interventional prevention trial for Pain, Postoperative focused on measuring pregabalin, total joint arthroplasty, side effect
Eligibility Criteria
Inclusion Criteria:
- clinical diagnosis of knee osteoarthritis;
- avascular necrosis of femoral head;
- dysplasia of the hip joint.
Exclusion Criteria:
- medical history of neuropathic pain or other non-arthritic chronic pain;
- Non-steroidal anti-inflammatory drug intolerance or long-term use of opioids;
- psychiatric disorders;
- motion sickness.
Sites / Locations
- The First Hospital of Jilin University
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Experimental
Arm Label
control group
study group
Arm Description
Oral administration of Pregabalin (75mg) 2h before operation; and oral administration of Pregabalin (75mg) at 18 pm from the first day after operation to discharge.
Oral administration of Pregabalin (37.5mg) at 8 am and 18 pm 1 d before operation; oral administration of Pregabalin (75mg) 2h before operation; and oral administration of Pregabalin (75mg) at 18 pm from the first day after operation to discharge.
Outcomes
Primary Outcome Measures
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
dizziness
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Secondary Outcome Measures
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
nausea
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
vomiting
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
sedation
ssessed by The Richmond Agitation-Sedation Scale (RASS)
opioids consumption
calculated as a product of the morphine equivalence and count, and intraoperative or any postoperative opioids consumption were recorded
independent transfers at six hours post-op
calculated as a product of the morphine equivalence and count, and They were instructed to make safely independent postoperative transfers at six hours after extubation.
pain score
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
pain score
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
pain score
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
pain score
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
time to readiness for discharge
Time to readiness for dischargey was calculated by day.
time to readiness for independent transfers
Time to readiness for dischargey was calculated by hour.
Full Information
NCT ID
NCT04599894
First Posted
October 8, 2020
Last Updated
October 23, 2022
Sponsor
The First Hospital of Jilin University
1. Study Identification
Unique Protocol Identification Number
NCT04599894
Brief Title
Reducing Postoperative Side Effect of Pregabalin
Official Title
Effect of Application of Low Dose of Pregabalin in TJA Before the Day of Surgery on Reducing Postoperative Side Effect of This Medicine
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
November 1, 2020 (Actual)
Primary Completion Date
April 30, 2021 (Actual)
Study Completion Date
May 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Hospital of Jilin University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study was to determine 1) if pregabalin, when given 37.5 mg twice on the day before surgery, would be effective in reducing the early postoperative side effects including dizziness, nausea, vomiting and sedation of receiving pregabalin 75mg two hours pre-operatively and 75mg per day until the third postoperative day; and 2) whether this intervention affected the opioids consumption, and independent transfers at six hours post-op, time to readiness for independent transfers, time to readiness for discharge and pain or not.
Detailed Description
Study design This prospective randomized controlled clinical trial was conducted at our institution in accordance with the Declaration of Helsinki. The Institutional Review Board approved the study (IRB number IRB00008484). We registered the clinical trial on The ClinicalTrials.gov Protocol Registration (NCT04599894) before the enrolment of the first participant. Written informed consent was obtained from each patient.
Participant recruitment Patients were eligible for inclusion if they were between 18 and 80 years of age and scheduled for a primary TJA. Exclusion criteria included: medical history of neuropathic pain or other non-arthritic chronic pain; Non-steroidal anti-inflammatory drug intolerance or long-term use of opioids; psychiatric disorders; motion sickness.
Sample size estimation The sample size was based on a preliminary study (under the same synergy of medications, celecoxib (Pfizer) 400mg and pregabalin (Pfizer) 75mg two hours pre-operatively orally, on the day of surgery). The preliminary study demonstrated that only one patient fell dizziness postoperatively in ten consecutive TJA patients who received 37.5mg pregabalin twice on the day before surgery, while four patient fell dizziness postoperatively in ten consecutive TJA patients receiving none on the day before surgery. Therefore the sample size was calculated by comparing estimated proportion using the Chi-squared statistic, a sample size of 58 (29 per group) would reveal differences at the 5% level of significance, and with a power of 0.8.
Randomization A computer-generated randomization schedule was used to assign patients to one of two treatment groups. The schedule was created by the clinical research center of our hospital, which was not involved in the clinical care of patients or in the conduct of the present trial.
Treatment protocol All patients scheduled to undergo primary TJA between November 2020 and April 2021 were screened for recruitment. Participants were recruited at their preoperative assessment visit two days before surgery and were randomly assigned to one of two treatment groups. Group 1 (G1) received pregabalin 37.5 mg twice orally (PO) on the day before surgery (at 8 am and 6 pm, respectively), and celecoxib 400mg as well as pregabalin 75mg PO at two hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose of celecoxib and pregabalin PO at two hours pre-operatively. Crystalloid for resuscitation was started on the morning of surgery. Perioperative antibiotics, cefazolin sodium, 2g, and tranexamic acid 1g were administered within one hour of skin incision via intravenous (IV) drip. Dolasetron 12.5mg IV and dexamethasone 5mg IV were administrated during the induction of anesthesia. Patients were sedated with midazolam and received a general anesthesia combined with fascia iliaca compartment block (FICB) for THA(0.2% ropivacaine 60mg for each joint) and adductor canal as well as infiltration between the popliteal Artery and Capsule of the Knee (iPACK) block for TKA (totally 0.2% ropivacaine 60mg for each joint). All procedures were performed by one group of surgeons (QX, GYH, ZXY, ZJT) through a posterolateral approach for THA and medial parapatellar approach for TKA. Periarticular injection (0.2% ropivacaine 80mg, compound betamethasone 7mg, ketorolac 30mg, epinephrine 0.3mg for each joint) was performed before implanting prosthesis. Cementless prosthesis (Depuy, Corail® Total Hip System) was used in all hips, and cemented prosthesis (Depuy, Attune® Total Knee System) was used in all knees. Neither drain was used in all wounds, nor was urinary catheter. IV patient-controlled analgesia (PCA) was not administered in these participants. Since two hours after extubation under general anesthesia, participants were allowed to drink water and progressively transit to their daily diaries. They were instructed to make independent postoperative transfers at six hours after extubation, which was taken as the final time point to determine the success of EARS pathway. Then these patients were transferred to a rehabilitation unit in the same hospital, cryotherapy and rehabilitation protocols were ordered until discharge. Rivaroxaban (10mg at 8 am per day, Bayer), celecoxib (200mg twice a day, at 8 am and 2 pm, respectively) as well as pregabalin (75mg per day at 6 pm) until the third postoperative day. Patients were instructed to maintain a VAS (visual analogous scale) pain score of between 1 and 3. If the VAS pain score was ≥4 at rest, oxycodone-acetaminophen (5mg/325mg, per dose, Mallinckrodt Inc.) would be used every six hours as needed for postoperative rescue analgesia. The discharge criteria included: patients' general well-being and acceptable pain control (VAS<4); dry wound; ability to safely mobilize with crutches and climb the stairs; patients' express acceptance of discharge; patients and family members learned the home-based exercise protocols for the first six weeks. Rivaroxaban was continued to use for five weeks. Cryotherapy, rehabilitation protocols and celecoxib 200mg twice a day were continued to use for six weeks postoperatively.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Arthroplasty, Replacement, Knee, Arthroplasty, Replacement, Hip
Keywords
pregabalin, total joint arthroplasty, side effect
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
control group
Arm Type
Sham Comparator
Arm Description
Oral administration of Pregabalin (75mg) 2h before operation; and oral administration of Pregabalin (75mg) at 18 pm from the first day after operation to discharge.
Arm Title
study group
Arm Type
Experimental
Arm Description
Oral administration of Pregabalin (37.5mg) at 8 am and 18 pm 1 d before operation; oral administration of Pregabalin (75mg) 2h before operation; and oral administration of Pregabalin (75mg) at 18 pm from the first day after operation to discharge.
Intervention Type
Drug
Intervention Name(s)
37.5mg Pregabalin + 75mg Pregabalin
Intervention Description
37.5mg pregabalin preoperatively + 75mg pregabalin postoperatively
Intervention Type
Drug
Intervention Name(s)
75mg Pregabalin
Intervention Description
75mg pregabalin postoperatively
Primary Outcome Measure Information:
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at the night pre-operatively (at 8 pm)
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours pre-operatively
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours post-operatively
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at four hours post-operatively
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at six hours post-operatively
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 1 (at 8 am)
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 2 (at 8 am)
Title
dizziness
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 3 (at 8 am)
Secondary Outcome Measure Information:
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at the night pre-operatively (at 8 pm)
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours pre-operatively
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours post-operatively
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at four hours post-operatively
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at six hours post-operatively
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 1 (at 8 am)
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 2 (at 8 am)
Title
nausea
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 3 (at 8 am)
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at the night pre-operatively (at 8 pm)
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours pre-operatively
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at two hours post-operatively
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at four hours post-operatively
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
at six hours post-operatively
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 1 (at 8 am)
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 2 (at 8 am)
Title
vomiting
Description
assessed on a 4-point verbal rating scale (VRS) (none, mild, moderate and severe)
Time Frame
on the morning of postoperative day (POD) 3 (at 8 am)
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
at the night pre-operatively (at 8 pm)
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
at two hours pre-operatively
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
at two hours post-operatively
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
at four hours post-operatively
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
at six hours post-operatively
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
on the morning of postoperative day (POD) 1 (at 8 am)
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
on the morning of postoperative day (POD) 2 (at 8 am)
Title
sedation
Description
ssessed by The Richmond Agitation-Sedation Scale (RASS)
Time Frame
on the morning of postoperative day (POD) 3 (at 8 am)
Title
opioids consumption
Description
calculated as a product of the morphine equivalence and count, and intraoperative or any postoperative opioids consumption were recorded
Time Frame
from surgery day to discharge day
Title
independent transfers at six hours post-op
Description
calculated as a product of the morphine equivalence and count, and They were instructed to make safely independent postoperative transfers at six hours after extubation.
Time Frame
at six hours post-operatively
Title
pain score
Description
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
Time Frame
at six hours post-operatively
Title
pain score
Description
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
Time Frame
on the morning of postoperative day (POD) 1 (at 8 am)
Title
pain score
Description
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
Time Frame
on the morning of postoperative day (POD) 2 (at 8 am)
Title
pain score
Description
Pain scores at rest and mobilization were assessed using VAS (0=no pain; 10=worst pain)
Time Frame
on the morning of postoperative day (POD) 3 (at 8 am)
Title
time to readiness for discharge
Description
Time to readiness for dischargey was calculated by day.
Time Frame
from the day of independent transfers to the day of meeting discharge criteria
Title
time to readiness for independent transfers
Description
Time to readiness for dischargey was calculated by hour.
Time Frame
from the hour of extubation to the hour of independent transfers
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
clinical diagnosis of knee osteoarthritis;
avascular necrosis of femoral head;
dysplasia of the hip joint.
Exclusion Criteria:
medical history of neuropathic pain or other non-arthritic chronic pain;
Non-steroidal anti-inflammatory drug intolerance or long-term use of opioids;
psychiatric disorders;
motion sickness.
Facility Information:
Facility Name
The First Hospital of Jilin University
City
Changchun
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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Reducing Postoperative Side Effect of Pregabalin
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