Safety and Efficacy of Pre-emptive Tapentadol vs Pregabalin in Post Operative Pain Following Surgery
Keywords
Abstract
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.
Dates
| Last Verified: | 05/31/2020 |
| First Submitted: | 07/18/2018 |
| Estimated Enrollment Submitted: | 07/25/2018 |
| First Posted: | 07/26/2018 |
| Last Update Submitted: | 06/23/2020 |
| Last Update Posted: | 06/24/2020 |
| Actual Study Start Date: | 07/31/2018 |
| Estimated Primary Completion Date: | 03/23/2020 |
| Estimated Study Completion Date: | 05/18/2020 |
Condition or disease
Intervention/treatment
Drug: Tapentadol
Drug: Pregabalin
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: Pregabalin Pregabalin 150mg oral tablets before one hour before undergoing unilateral total knee arthroplasty | Drug: Pregabalin This arm will receive drugs one hour before undergoing unilateral total knee arthroplasty. Interventions pregabalin 150mg oral tablets. |
| Experimental: Tapentadol tapentadol 100mg oral tablets before one hour before undergoing unilateral total knee arthroplasty | Drug: Tapentadol This arm will receive drugs one hour before undergoing unilateral total knee arthroplasty. Interventions tapentadol 100mg oral tablets. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | 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. Exclusion Criteria: - 1.Patients with asthma, COPD 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. |
Outcome
Primary Outcome Measures
1. Efficacy and safety of pregabalin and tapentadol by measuring the mean difference in the mean VAS score. [Evaluated over 24hrs post unilateral total knee arthroplasty]
Secondary Outcome Measures
1. Comparing differences in TOTPAR scale through different time points of 24 hours Comparing differences in TOTPAR (none, mild, moderate and severe) scale through different time points of 24 hours [Recorded over 24hrs post unilateral total knee arthroplasty]
2. Measuring the rescue analgesic requirement in both the groups [Recorded over 24hrs post unilateral total knee arthroplasty]
3. Monitoring adverse events in both the groups including post-operative nausea vomiting (PONV) [Recorded over 24hrs post unilateral total knee arthroplasty]
4. Percentage of adverse events in a 4-point verbal scale. [Recorded over 24hrs post unilateral total knee arthroplasty]
5. Estimation of COX-2 at 0hrs and 6hrs post operatively in both the groups by ELISA. [In two blood samples one at 0hrs and 6hrs post operatively]
6. Reduction of VAS and nausea/vomiting [Evaluated at the end of 6 hours and 12 hours without nausea and vomiting]
