Clinical trial NCT04599894: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Arthroplasty, Replacement, Knee
Arthroplasty, Replacement, Hip
Keywords: pregabalin
total joint arthroplasty
side effect
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
First posted: 2020-10-23
Enrollment: 58
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: dizziness
timeFrame: at the night pre-operatively (at 8 pm)
measure: dizziness
timeFrame: at two hours pre-operatively
measure: dizziness
timeFrame: at two hours post-operatively
measure: dizziness
timeFrame: at four hours post-operatively
measure: dizziness
timeFrame: at six hours post-operatively
measure: dizziness
timeFrame: on the morning of postoperative day (POD) 1 (at 8 am)
measure: dizziness
timeFrame: on the morning of postoperative day (POD) 2 (at 8 am)
measure: dizziness
timeFrame: on the morning of postoperative day (POD) 3 (at 8 am)
Secondary outcomes:
measure: nausea
timeFrame: at the night pre-operatively (at 8 pm)
measure: nausea
timeFrame: at two hours pre-operatively
measure: nausea
timeFrame: at two hours post-operatively
measure: nausea
timeFrame: at four hours post-operatively
measure: nausea
timeFrame: at six hours post-operatively
measure: nausea
timeFrame: on the morning of postoperative day (POD) 1 (at 8 am)
measure: nausea
timeFrame: on the morning of postoperative day (POD) 2 (at 8 am)
measure: nausea
timeFrame: on the morning of postoperative day (POD) 3 (at 8 am)
measure: vomiting
timeFrame: at the night pre-operatively (at 8 pm)
measure: vomiting
timeFrame: at two hours pre-operatively
measure: vomiting
timeFrame: at two hours post-operatively
measure: vomiting
timeFrame: at four hours post-operatively
measure: vomiting
timeFrame: at six hours post-operatively
measure: vomiting
timeFrame: on the morning of postoperative day (POD) 1 (at 8 am)
measure: vomiting
timeFrame: on the morning of postoperative day (POD) 2 (at 8 am)
measure: vomiting
timeFrame: on the morning of postoperative day (POD) 3 (at 8 am)
measure: sedation
timeFrame: at the night pre-operatively (at 8 pm)
measure: sedation
timeFrame: at two hours pre-operatively
measure: sedation
timeFrame: at two hours post-operatively
measure: sedation
timeFrame: at four hours post-operatively
measure: sedation
timeFrame: at six hours post-operatively
measure: sedation
timeFrame: on the morning of postoperative day (POD) 1 (at 8 am)
measure: sedation
timeFrame: on the morning of postoperative day (POD) 2 (at 8 am)
measure: sedation
timeFrame: on the morning of postoperative day (POD) 3 (at 8 am)
measure: opioids consumption
timeFrame: from surgery day to discharge day
measure: independent transfers at six hours post-op
timeFrame: at six hours post-operatively
measure: pain score
timeFrame: at six hours post-operatively
measure: pain score
timeFrame: on the morning of postoperative day (POD) 1 (at 8 am)
measure: pain score
timeFrame: on the morning of postoperative day (POD) 2 (at 8 am)
measure: pain score
timeFrame: on the morning of postoperative day (POD) 3 (at 8 am)
measure: time to readiness for discharge
timeFrame: from the day of independent transfers to the day of meeting discharge criteria
measure: time to readiness for independent transfers
timeFrame: from the hour of extubation to the hour of independent transfers
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
Study officials:
References: