This prospective, triple blind, split-mouth, cross-over, study was conducted at the Department of Oral and Maxillofacial Surgery, from January 2018 to November 2019.
Calculation of sample size
The sample size of 24 patients (48 extraction sites) was calculated using reference values from previous literature8 using the following formula:
Where, Zµ/2=1.96 (Critical Z value for α at 95% CI)
Zβ=0.84 (Critical Z value for β at 80%)
P1=70; P2= 32 (Proportion incidence of groups 1 and 2)
Inclusion and exclusion criteria
Patients between age 18 to 40 years indicated for bilateral third molar surgery with Class 2 Position B Mesioangular Impaction with the difficulty index 5-9 on both sides were selected for the study. While patients with history of acute localized periapical infection or cyst or granuloma associated with the tooth to be extracted, known allergy to Tramadol or Tapentadol or those taking narcotics, centrally acting analgesic, opioids or psychotropic drugs were excluded from the study. Informed consent was obtained from all patients. The study was started after obtaining permission from ethics committee.
No deviations from the original protocol were necessary or occurred during the course of the trial
Patient selection, randomization and allocation
24 patients who fit the inclusion criteria were selected for the study. The total number of extraction site was 48.[Figure 1]
For allocation, patients were randomly assigned by simple randomization with a 1:1 allocation ratio to Tapentadol or Tramadol.
Since this was a cross-over study design, the sequence generation for allocation of the tablet and the site of extraction was decided by SNOSE(sequentially numbered opaque sealed envelopes).The opaque sealed envelope contained the name of the drug and which side tooth had to be extracted first (right or left). Group A represented patients who received Tapentadol (Tablet Tydol 50mg) and Group B represented patients who received Tramadol (Tablet Ultratram-P 50mg). The operator (SM), the co-investigator (KB) who recorded the visual analogue scale (VAS) scores and the statistician (PK) were blinded to the medicine and side for which it was used. The patient enrollment and allotment was done independently by third researcher (MG).
Procedure
Detailed case history and an informed written consent was obtained from all patients. Before starting the procedure, the use of VAS was explained to the patients. The same operator (SM) carried out all the surgical procedures to avoid any bias in the study. Local anesthetic injection (Lox 2% adrenaline 1:200000, Neon Laboratories Ltd, India) was administered using classical inferior alveolar nerve block. Thirty gauge and 1.5-inch-long needles were used for the injection. Surgical removal of the mandibular third molar was done using standard surgical protocol.
Antibiotics (Tablet Augmentin 625mg two times a day for 5 days) were prescribed for all patients. Additionally, for group A, Tablet Tydol 50mg two times a day for 5 days was given and for group B, Tablet Ultratram-P 50mg was given two times a day for 5 days. Rescue medication-Piroxicam (Tab.Dolonex DT 20mg) was also provided to the patient.
Ten point VAS (where 0 implied no pain and 10 implied worst possible pain) was used to record the pain score by a blinded co-investigator (KB) on the next day (post-operative day1 i.e. POD1) and on the 5th post-operative day (POD5). The number of rescue medications required were also noted for POD1. Suture removal was done on the 7th post-operative day.
A wash out period of three weeks was observed and same surgical procedure, medication protocol was followed for the surgical removal of the other third molar and VAS was recorded again.
The primary outcome measure was the pain felt on POD1 and POD5 which was reported by the patient, using the VAS of 0 – 10,
STATISTICAL ANALYSIS
The data was analyzed using SPSS for Windows version 16.0 (IBM Corp., USA). Wilcoxon Signed Rank test was used for Intra-group comparison of VAS on POD1 and POD5. Mann Whitney U test was used for Inter-group comparison of VAS on POD1 and POD5. Mann Whitney U test was used for Inter-group comparison of rescue medications taken on POD0 and POD1.The level of significance was fixed at p<0.05.