Effectiveness of Peri-operative Combined Use of 2 Doses of Dexamethasone With Tranexamic Acid in Lower Limb Joint Replacements- A Randomized Controlled Trial.
Phase: NA
Conditions: Hip Replacement, Knee Replacement
Sponsor: Indus Hospital and Health Network

OFFICIAL TITLE: EFFECTIVENESS OF PERI-OPERATIVE COMBINED USE OF 2 DOSES OF 
DEXAMETHASONE WITH TRANEXAMIC ACID IN LOWER LIMB JOINT REPLACEMENTS, A 
RANDOMIZED CONTROLLED TRIAL 
 
DATE OF DOCUMENT:  APPROVED BY INSTITUTIONAL REVIEW BOARD, INDUS 
HOSPITAL ON 11/07/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
1 
INTRODUCTION/BACKGROUND 
Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are highly effective interventions 45 for 
end-stage arthritis of the knee and hip. Controlling postoperative pain and nausea after total joint 
arthroplasty remains an important challenge. Perioperative corticosteroids are safe, facilitate earlier 
discharge, and improve patient recovery following unilateral total knee arthroplasty and total hip 
arthroplasty. Higher doses (15-20 mg of dexamethasone) are associated with further reductions in 
dynamic pain and PONV, and repeat dosing may further reduce LOS. It was found that neither one nor 
two doses of 24 mg intravenous dexamethasone demonstrated prolonged effects on overall pain or 
sleep quality on postoperative days 3–7 after total knee arthroplasty, also have no effect on patients 
satisfaction, but it reduced the opioid consumption. Tranexamic acid (TXA) reduces rates of blood 
transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA) . Hence, it was proved that  
the combination of TXA and DEX has positive impacts on the usage of oxycodone and metoclopramide, 
postoperative range of motion, postoperative nausea and vomiting and reduces the length of hospital 
stay .The administration of 10 mg dexamethasone 1 h before the surgery, and repeated at 6 h 
postoperatively can significantly reduce the level of postoperative CRP and IL-6. There is insufficient 
evidence on perioperative dexamethasone in primary TJA to determine the optimal dose, number of 
doses, or risk of postoperative adverse events. 
 
2 .Background of interventional procedure  
Total joint arthroplasty (TKA) is viewed as one of the most successful orthopedic surgeries for most end-
stage joint diseases. In recent years, the concept of enhanced recovery after surgery (ERAS) has greatly 
improved the speed of rehabilitation after total joint arthroplasty. Patients feel more comfortable 
during the perioperative period and have shorter hospital stays with the administration of steroidal 
administration. Dexamethasone plays an important role in ERAS due to its anti-inflammatory and pain 
reduction role. As, TXA can prevent the activation of plasminogen and delay fibrinolysis and reduce 
blood loss and the rate of blood transfusion perioperatively. Recent studies showed that 
dexamethasone may be administered multiple times peri operatively. A large number of studies 
confirmed that dexamethasone can reduce post operative pain and inflammation and shortens the 
length of hospital stay and combination pre operative tranexamic acid with dexamethasone reduces the 
limb swelling that improves the joint range of motion. There will be no risk of the interventional drug 
Benefits will include that the drug is cost effective, easily available, reduce the post operative 
complications 
 

3. Rationale 
Previous studies showed the effects of peri-operative use of single dose of dexamethasone, and there is 
very little data available on effects of peri-op use of multiple doses of dexamethasone. There is no study 
that has been conducted yet, which compared the effects of peri-op use of 1 dose of dexamethasone 
and tranexamic acid with 2 doses of dexamethasone and tranexamic acid, on post operative range of 
motion and pain during rest and weight bearing on operated limb, length of stay in hospital and C-
reactive protein. 
 
4.  Study Objectives 
4.1 
Primary Objective  
To evaluate the effectiveness of peri operative intravenous 2 doses of dexamethasone in lower limb 
joint/s replacement surgeries on postoperative C-reactive protein, post operative fatigue, postoperative 
joint range, post operative pain during rest and weight bearing, and length of hospital stay. 
 
4.2   Hypothesis:  
If hypothesis will get confirmed, then the peri operative use of 2 doses of dexamethasone with 
intravenous tranexamic acid, reduces the postoperative C-reactive protein,  post operative fatigue,  pain 
during rest and weight bearing, and length of hospital stay and improves the post operative joint range 
of motion. 
 
If hypothesis will not get confirmed, then the peri operative use of 2 doses of dexamethasone with 
intravenous tranexamic acid, will not reduces the postoperative C-reactive protein,  post operative 
fatigue,  pain during rest and weight bearing, and length of hospital stay and and will not improve the 
post operative joint range of motion. 
 
 
5. Material and Methods: 
 
5.1 
Study Design: 
Randomized controlled trial with 2 arms 
Arm 1: GROUP A will receive 1 dose of dexamethasone (10mg) with tranexamic acid (20mg/kg), peri 
operatively . 
Arm 2: GROUP B will receive 2 doses of dexamethasone (2*10mg) with tranexamic acid (20mg/kg), peri 
operatively. 

 
5.2 
Study setting & target population 
Study settings: Orthopedics Department, Indus Hospital and Health Network. 
Targeted Population: patients having knee/hip osteoarthritis scheduled for joint replacement of one or 
both sides. 
 
5.3 
Duration of study 
12 months 
8 patients per month will be enrolled 
 
5.4 
Trial Population: 
 
Screening Criteria 
After giving the informed signed consent, participants will have a detailed examination and will assess 
for eligibility as defined in inclusion/exclusion criteria.   
5.5  Clinical contraindications 
                                Not any 
5.6 Excluded medications 
                             Not any 
5.7 Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their 
formulation 
Not any 
5.8 
Active drug or alcohol use or dependence that would interfere with adherence to study 
requirements 
Serious illness requiring systemic treatment and/or hospitalization within 3-4 days prior to entry 
               Not any 
 
6 
Study enrollment procedures including informed consent 
Prior to commencing the study, protocol and protocol consent form will be approved by the institutional 
review board (IRB). Once the identification will be completed, details will be carefully discussed with the 
subject.  

 If the patient or representative will not able to read and sign then informed, then it will be signed and 
dated by an impartial witness who will independent of the Investigator. A witness who will sign and date 
the consent form will certify that the information in this form and any other written information had 
been accurately explained to and understood by the patient or his / her representative. 
 
7            STUDY TREATMENT (OR INTERVENTION) 
7.1 
Regimens (or Intervention), Administration, and Duration 
All patients will randomize into two groups, 
 Group A: 1 dose of  IV Dexamethasone 10mg+ tranexamic acid (20 mg/kg);  
Group B: 2 doses of IV Dexamethasone 10mg+ tranexamic acid 20 mg/kg.  
In group A, 1 dose of 10 mg of intravenous dexamethasone and 20mg/kg of intravenous tranexamic acid 
administered at 10 minutes before surgery. 
In group B, dose of 10 mg of intravenous dexamethasone and 20mg/kg of intravenous tranexamic acid 
administered at 10 minutes before surgery and then 10mg of intravenous dexamethasone will be again 
administered before incision closure. 
 
7.2 
Concomitant Medications 
7.2.1 
Required Medications:         IV TXA 20 mg/kg 
                                                                 IV Dexamethasone 10mg 
                                                                    
7.2.2 
Prohibited Medications:                     not any 
7.2.3 
Precautionary Medications:              not any 
7.3 
Treatment Compliance (adherence assessment) 
Treatment compliance:  
If patient will come on follow up visits at 1st  and 4th week for outcomes assessment, after discharge. 
 
Treatment non compliance: 
If patient will not come on follow up visits at 1st and 4th week for outcomes assessment, after 
discharge.  
 
8 
CLINICAL AND LABORATORY EVALUATIONS 

 
 
8.1. Timing of Evaluations 
 
8.1.1 Screening: Screening will be done during pre operative evaluations, prior to the enrollment in 
study. In addition to data being collected on subjects who enroll into the study, demographic, clinical, 
and laboratory data on screening failures will be captured in a screening log and entered into the 
database. 
 
8.1.2  Pre-Entry  
Pre-entry evaluations will complete at 15 days after screening evaluations have been completed. 
 
8.1.3 Follow-up 
Follow up will take place at 1st and 4th week, after discharge. 
 
8.2 
Laboratory Evaluations 
Pre Operative laboratory evaluations will include: 
Complete Blood Count (CBC) 
C-Reactive Protein (CRP) 
Renal Function Test (RFT) 
Hepatitis B and C 
Electrocardiogram 
Chest X-ray 
Activated Partial Thrombin Time (aPTT) 
Prothrombin Time (PT) 
Hemoglobin A1c (HbA1c) 
 
Post operative laboratory evaluations 
Complete Blood Count (CBC) 
C-Reactive Protein (CRP) 

 
from which investigators will take data of C-reactive protein values in our study, to compare pre and 
post operatively. 
 
8.3 
Questionnaires 
• 
Post operative identity consequences fatigue rating scale 
• 
Numeric Pain rating Scale 
 
9 
CRITERIA FOR DISCONTINUATION 
9.1 
Permanent Treatment Discontinuation 
• 
Drug-related toxicity  
• 
Requirement for prohibited concomitant medications . 
• 
Not completion of treatment as defined in the protocol. 
• 
Request by subject to terminate treatment. 
• 
Clinical reasons believed life threatening by the physician, even if not addressed in the toxicity 
section of the protocol. 
 
9.2 
Premature Study Discontinuation 
• 
Failure by the subject to attend consecutive clinic visits at 1st week and 4th week after 
discharge. 
• 
Request by the subject to withdraw. 
• 
Request of the primary care provider if s/he thinks the study is no longer in the best interest of 
the subject. 
• 
Subject judged by the investigator to be at significant risk of failing to comply with the provisions 
of the protocol as to cause harm to self or seriously interfere with the validity of the study results. 
• 
A defined study endpoint reached. 
• 
At the discretion of the IRB or investigator.  
from which investigators will take data of C-reactive protein values in our study 
 
 

10 
STATISTICAL CONSIDERATIONS  
 
10.1 
Blinding Procedures  
The patients, trial participants, anesthesiologists, and data collectors will be blinded to allocation while 
assessors will know the allocation. 
 
10.2 
Sample Size and Accrual 
 IBM SPSS Statistics 21 software will be used to analyze the data. 
Methods of analyzing the data will include interferential and descriptive statistics 
10.3 
Determination of Sample Size and Power Calculation 
The calculated sample size, using total blood loss is 25 in each group and after adding 20% dropout the 
sample size will be 25+5=30 in each group. The sample size is calculated using following information. 
Z1-α/2 Level of significance=95%   
µ1 Expected mean change in total blood loss in Group A=93.80 
µ2 Expected mean change in total blood loss in Group B= 95.98 
 δ1 Expected standard deviation in group A=3.88 
 δ2 Expected standard deviation in group B=2.82 
Z1-β power of the study= 80%  
 sample size in a group(n)= 38 
After adding 20% drop out 38+8=46 in each group.   
Total sample size will be 92 
 No of groups/arms in study: 
Type of comparison:   
Superiority comparison 
Type of configuration:  
Parallel designs 
Level of significance (Alpha level): 95 % 
Power:  0.8 or 80 %  
Allocation ratio:  1:1 

Underlying population event rate:  
Almost 90 percent of population undergoing total joint replacement, whether uni or bilateral would 
show the positive clinical outcomes with the use of 2 doses of dexamethasone. 
Effect size of therapy: the clinical guidelines shows that each group of clinical trial must have at least  30 
participants, so effect size is 92 more than sample size calculated, drop out patients percentages added. 
Estimated loss to follow-up or refusals:  Based on previous work in this population, 20 % will be lost to 
follow up or drop out from the trial. 
10.4    Underlying population event rate:  
The population enrolled in previous studies undergoing total joint replacement, whether unilateral or 
bilateral showed the positive clinical outcomes with the use of dexamethasone with tranexamic acid. 
10.5    Estimated loss to follow-up or refusals:  Based on previous work in this population, 20 % will be 
lost to follow up or drop out from the trial. 
 
11 
DATA MANAGEMENT AND MONITORING  
11.1 
Key personal description 
ROLE OF INVESTIGATOR: supervise and guidance of all study protocols 
ROLE OF CO-INVESTIGATOR: allocation, screening and reassessments, at follow ups, of patients. 
ROLE OF NURSING STAFF: taking data from patients under supervision of co-investigators. 
. 
11.2 
Monitoring of clinical staff involved in research 
Nursing staff will be trained about data collection by mentioning the pre and post op CRP,  measuring 
the knee ROMS with goniometer, post operative fatigue scoring, length of hospital stay, post operative 
pain scoring that will be measured as under supervision of co-investigators. 
11.3 
Records to be kept 
Total 4 questionnaires will be provided for each subject to record the data pre and post operative 1st 
day, 1st and 4th week after discharge. Subjects will be identified by the patient medical record number 
(MR no). 
11.4 
Management of Clinical Data 
The patient’s data will be kept on the red cap software, and assessor will assign the patients into 2 
groups such that group A and B, according to the doses of dexamethasone will be given, but data 
collector and patients will be unaware of the group randomization. 
   
11.5 
Lost to Follow-up Procedures 

. A documented reasonable effort i.e., documented telephone calls will be undertaken to locate or recall 
them, or at least to determine their health status while fully respecting their rights. These efforts will be 
documented in the research file in the case of patients who fail to return for a follow-up examination. 
 
11.6 
Follow-up of Discontinuations 
The research team will complete all scheduled safety follow-ups with any patient who has prematurely 
terminated the trial because of a Serious Adverse Event, non-compliance with the protocol, or loss of 
eligibility, including definite contraindications 
 
11.7 
Clinical Site Monitoring and Record Availability 
Data will be collected from patients in orthopedics ward, and records will be available on Red Cap forms. 
 
12 
ADVERSE EVENTS DATA MANAGEMENT & REPORTING  
12.1 
Safety Definitions 
12.1.1 Adverse Event (AE): 
                            Not any 
12.1.2 Adverse Reaction: 
                            Not any 
 
13 
HUMAN SUBJECTS 
IRB OF INDUS HOSPITAL AND HEALTH NETWORK 
APPROVAL LETTER BY IRB-INDUS HOSPITAL 
 
Expedited v2- IRB Approval letter.pdf
 
 
14. Data collection instruments 
It includes 4 questionnaire forms per patient 
Pre operative form: 

PreOpt_EFFECTIVENESSOFPERIOPER.pdf
 
Post operative 1st day form 
PostOp_EFFECTIVENESSOFPERIOPER.pdf
 
Post operative 1st week after discharge from hospital, form 
1stWeekAfterDischarge_EFFECTIV.pdf
 
Post operative 4th week after discharge from hospital, form 
4thWeekAfterDischarge_EFFECTIV.pdf