Safety and Efficacy of Pre-emptive Tapentadol vs Pregabalin in Post Operative Pain Following Surgery
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis, Knee; Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      Preemptive analgesia is a treatment modality which starts even before the surgery, so that
      the central sensitization is prevented due to incisional injury at the time of surgery, so it
      covers the period of surgery and initial post-operative period preventing the development of
      central sensitization.

      Gabapentinoid compounds are gabapentin and pregabalin which have been extensively used in
      seizure disorder patient. Role of gabapentinoid compounds in the management of pain, as a
      pre-emptive analgesia is yet to be completely evaluated in post operative pain. Opioids have
      always been the preferred drugs to manage post operative pain. Since opioids have major side
      effects of nausea vomiting associated with its treatment their use comes with management of
      these side effects.

      Currently, diagnostic and therapeutic approaches to manage pain experienced by individuals
      are limited especially because there's a lack of bio-markers predictive of therapeutic
      outcome. In search of an objective method for pain measurement, as pain has always been
      subjective and it is perceived by different people differently the study will also include
      finding the use of COX(cyclo-oxygenase)-2 as a bio-marker of pain in post-operative patients.

      Although several randomized clinical trials and met-analyses have been conducted comparing
      the safety and efficacy of tapentadol or pregabalin in post-operative pain, there is no head
      to head clinical trial conducted comparing the preemptive use of two drugs for postoperative
      pain following total knee arthroplasty (TKA). Hence the present study is planned.
    

Detailed description: 
      MATERIALS AND METHODS

      After approval of the institutional Ethics committee board, written informed consent will be
      taken from all the eligible and willing patients.

      A. Study design: Randomized double blind active controlled parallel group noninferiority
      clinical trial.

      B. Randomization: A variable block randomization. The allocation ratio will be 1:1 ratio
      between two interventions arms i.e. tapentadol 100 mg(milligram) and pregabalin 150
      mg(milligram) orally.

      C. Allocation concealment: This study will be participant and investigator blinded.
      Allocation concealment will be done by sequentially numbered sealed drug pouches.

      D. Study site: Department of Pharmacology and Orthopedics of AIIMS, Bhubaneswar.

      Selection Criteria

      A. Inclusion criteria

        1. Patients both males and females undergoing total knee arthroplasty surgery.

        2. Patients are capable of providing an informed consent.

        3. Age group between 18-75 years.

      B. Exclusion criteria

        1. Patients with asthma, COPD(Chronic obstructive pulmonary disease) or any other
           respiratory disease.

        2. Persistent nausea and vomiting at time of randomization

        3. Epilepsy.

        4. Treated with mono amine oxidase inhibitors, tricyclic antidepressants, serotonin
           norepinephrine re-uptake inhibitors, gabapentinoids.

        5. Patient with known neurological/ neuropsychiatric disorders.

        6. Drug or alcohol abuse history

        7. Opioid tolerance or opioid dependence.

        8. Known history of opioid allergy or pregabalin allergy.

        9. Renal disease (creatinine >1.5mg/dl)

       10. Liver disease (total bilirubin >1.5mg/dl)

       11. Pregnancy and lactation.

       12. Cardiovascular insufficiency.

       13. Patient with potential serotonin syndrome.

       14. Patient with history of constipation and prone to paralytic ileus.

      Study procedure, tools & evaluation

        1. Consent: Patients will be explained the benefit and harm of joining the study and
           freedom of withdrawing from the study any moment they would like to. A full voluntary
           written informed consent will be obtained from each patient. Study will be conducted
           following the principles of Helsinki after getting written permission of the
           institutional ethics committee. Before enrolment of first patient in this study
           registration for clinical trial will be done.

        2. All the patients will be screened before enrollment after eliciting detailed history
           they will undergo complete medical and laboratory examinations.

        3. A total of 90 patients of either sex will be selected randomly and will be assigned to
           receive 100 mg of Tapentadol or 150mg Pregabalin orally 1hr before surgery in a
           double-blind manner. The patient will be assessed for pain at 0,6,12, and 24hrs, post
           operatively by visual analogue scale score(VAS) (0-100). Pain measurements will also be
           done on TOTPAR scale at 0,6,12,24 hours. Total rescue analgesic consumption also will be
           assessed at 24hrs post operatively. All treatment emergent adverse events will be
           documented. The time to 1st patient request for supplemental analgesia also will be
           recorded.

        4. A blood sample will be obtained from each of the patients twice once at 0 hrs. and again
           at 6hrs post operatively to evaluate concentration of COX-2 levels by ELISA with
           commercially available ELISA kits.
    

Intervention name(s): Tapentadol 100 MG Oral Tablet; Pregabalin 150mg
Intervention type(s): Drug; Drug
Intervention description(s): This arm will receive drugs one hour before undergoing unilateral total knee arthroplasty. Interventions tapentadol 100mg oral tablets.; This arm will receive drugs one hour before undergoing unilateral total knee arthroplasty. Interventions pregabalin 150mg oral tablets.
Intervention MeSH terms: Pregabalin; Tapentadol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: OA knee,pre-emptive analgesia,TKA,Opioids,gabapentinoids