Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06653699
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-05
Brief Title:
Effectiveness of Peri-operative Combined Use of 2 Doses of Dexamethasone With Tranexamic Acid in Lower Limb Joint Replacements-A Randomized Controlled Trial
Sponsor:
None
Organization:
None
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this randomized controlled clinical trial is to investigate the effectiveness of peri operative use of 2 doses of dexamethasone with tranexamic acid in lower limb replacement on post operative C-reactive protein CRP joint range of motion fatigue pain hospital length of stay in malefemale patients undergoing lower limb joint replacement with pre op Hb above 10gdL
The main question it aims to answer The peri operative use of 2 doses of dexamethasone with tranexamic acid in lower limb replacement decrease the post operative CRP fatigue pain hospital length of stay and increase the joint range of motion
Researcher will compare the two groups without knowing which group received either of 1 or 2 doses of Dexamethasone with TXA peri operatively
Patients will do answer the questions mentioned in questionnaire pre operatively at post op 1st day at 1st week and 4th week post discharge
The main question it aims to answer The peri operative use of 2 doses of dexamethasone with tranexamic acid in lower limb replacement decrease the post operative CRP fatigue pain hospital length of stay and increase the joint range of motion
Researcher will compare the two groups without knowing which group received either of 1 or 2 doses of Dexamethasone with TXA peri operatively
Patients will do answer the questions mentioned in questionnaire pre operatively at post op 1st day at 1st week and 4th week post discharge
Detailed Description:
1 INTRODUCTIONBACKGROUND 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
Primary Objective
To evaluate the effectiveness of peri operative intravenous 2 doses of dexamethasone in total lower limb joint 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
42 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
51 Study Design Randomized controlled trial with 2 arms Arm 1 GROUP A will receive 1 dose of dexamethasone 10mg with tranexamic acid 20mgkg peri operatively
Arm 2 GROUP B will receive 2 doses of dexamethasone 210mg with tranexamic acid 20mgkg peri operatively
52 Study setting target population Study settings Orthopedics Department Indus Hospital and Health Network Targeted Population patients having kneehip osteoarthritis scheduled for joint replacement of one or both sides
53 Duration of study 12 months 8 patients per month will be enrolled
54 Trial Population
Screening Criteria
After giving the informed signed consent participants will have a detailed examination and will assess for eligibility as defined in inclusionexclusion criteria
55 Clinical contraindications Not any 56 Excluded medications Not any 57 Known allergysensitivity or any hypersensitivity to components of study drugs or their formulation Not any 58 Active drug or alcohol use or dependence that would interfere with adherence to study requirements Serious illness requiring systemic treatment andor 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 71 Regimens or Intervention Administration and Duration All patients will randomize into two groups Group A 1 dose of IV Dexamethasone 10mg tranexamic acid 20 mgkg Group B 2 doses of IV Dexamethasone 10mg tranexamic acid 20 mgkg
In group A 1 dose of 10 mg of intravenous dexamethasone and 20mgkg of intravenous tranexamic acid administered at 10 minutes before surgery
In group B dose of 10 mg of intravenous dexamethasone and 20mgkg of intravenous tranexamic acid administered at 10 minutes before surgery and then 10mg of intravenous dexamethasone will be again administered before incision closure
72 Concomitant Medications 721 Required Medications IV TXA 20 mgkg IV Dexamethasone 10mg
722 Prohibited Medications not any 723 Precautionary Medications not any 73 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
81 Timing of Evaluations
811 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
812 Pre-Entry Pre-entry evaluations will complete at 15 days after screening evaluations have been completed
813 Follow-up Follow up will take place at 1st and 4th week after discharge
82 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 investigator will take data of C-reactive protein values in our study to compare pre and post operatively
83 Questionnaires
Surgical Recovery Scale SRS-Short form of Post operative identity consequences fatigue rating scale
Numeric Pain rating Scale
9 CRITERIA FOR DISCONTINUATION 91 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
92 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 she 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 investigator will take data of C-reactive protein values in this study
10 STATISTICAL CONSIDERATIONS
101 Blinding Procedures The patients trial participants anesthesiologists and data collectors will be blinded to allocation into two groups while assessors will know the allocation
102 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 Descriptive statistics of demographics and outcome measure variables will be calculated in form of mean standard deviation
Interferential statistics will include comparison of variables within and in between both groups
Comparison of all outcome variables will be measured according to normality of data which will be assessed by data normality tests included Kolmogorov-Smirnov and the Shapiro Wilk Test
1021 Within group If data will be normally distributed then paired sample t-test will be applied within group If data will be not normally distributed then Wilcoxon signed rank test will be applied 1022 In between groups If data will be normally distributed then independent sample t-test will be applied within group If data will be not normally distributed then Mann Whittney U-test will be applied
103 Determination of Sample Size and Power Calculation
Z1-α2 Level of significance95 µ1 Expected mean change in total blood loss in Group A9380 µ2 Expected mean change in total blood loss in Group B 9598 δ1 Expected standard deviation in group A388 δ2 Expected standard deviation in group B282 Z1-β power of the study 80 sample size in a groupn 38 After adding 20 drop out 38846 in each group Total sample size will be 92 1031 Type of comparison Superiority comparison 1032 Type of configuration Parallel designs 1033 Level of significance Alpha level 95 1034 Power 08 or 80 1035 Allocation ratio 11 1036 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
1037 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 111 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
112 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
113 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
114 Management of Clinical Data The patients 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
115 Lost to Follow-up Procedures
A documented reasonable effort ie 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
116 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
117 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 121 Safety Definitions 1211 Adverse Event AE Not any 1212 Adverse Event SAE Not any 1213 Adverse Reaction Not any
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
Primary Objective
To evaluate the effectiveness of peri operative intravenous 2 doses of dexamethasone in total lower limb joint 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
42 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
51 Study Design Randomized controlled trial with 2 arms Arm 1 GROUP A will receive 1 dose of dexamethasone 10mg with tranexamic acid 20mgkg peri operatively
Arm 2 GROUP B will receive 2 doses of dexamethasone 210mg with tranexamic acid 20mgkg peri operatively
52 Study setting target population Study settings Orthopedics Department Indus Hospital and Health Network Targeted Population patients having kneehip osteoarthritis scheduled for joint replacement of one or both sides
53 Duration of study 12 months 8 patients per month will be enrolled
54 Trial Population
Screening Criteria
After giving the informed signed consent participants will have a detailed examination and will assess for eligibility as defined in inclusionexclusion criteria
55 Clinical contraindications Not any 56 Excluded medications Not any 57 Known allergysensitivity or any hypersensitivity to components of study drugs or their formulation Not any 58 Active drug or alcohol use or dependence that would interfere with adherence to study requirements Serious illness requiring systemic treatment andor 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 71 Regimens or Intervention Administration and Duration All patients will randomize into two groups Group A 1 dose of IV Dexamethasone 10mg tranexamic acid 20 mgkg Group B 2 doses of IV Dexamethasone 10mg tranexamic acid 20 mgkg
In group A 1 dose of 10 mg of intravenous dexamethasone and 20mgkg of intravenous tranexamic acid administered at 10 minutes before surgery
In group B dose of 10 mg of intravenous dexamethasone and 20mgkg of intravenous tranexamic acid administered at 10 minutes before surgery and then 10mg of intravenous dexamethasone will be again administered before incision closure
72 Concomitant Medications 721 Required Medications IV TXA 20 mgkg IV Dexamethasone 10mg
722 Prohibited Medications not any 723 Precautionary Medications not any 73 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
81 Timing of Evaluations
811 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
812 Pre-Entry Pre-entry evaluations will complete at 15 days after screening evaluations have been completed
813 Follow-up Follow up will take place at 1st and 4th week after discharge
82 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 investigator will take data of C-reactive protein values in our study to compare pre and post operatively
83 Questionnaires
Surgical Recovery Scale SRS-Short form of Post operative identity consequences fatigue rating scale
Numeric Pain rating Scale
9 CRITERIA FOR DISCONTINUATION 91 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
92 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 she 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 investigator will take data of C-reactive protein values in this study
10 STATISTICAL CONSIDERATIONS
101 Blinding Procedures The patients trial participants anesthesiologists and data collectors will be blinded to allocation into two groups while assessors will know the allocation
102 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 Descriptive statistics of demographics and outcome measure variables will be calculated in form of mean standard deviation
Interferential statistics will include comparison of variables within and in between both groups
Comparison of all outcome variables will be measured according to normality of data which will be assessed by data normality tests included Kolmogorov-Smirnov and the Shapiro Wilk Test
1021 Within group If data will be normally distributed then paired sample t-test will be applied within group If data will be not normally distributed then Wilcoxon signed rank test will be applied 1022 In between groups If data will be normally distributed then independent sample t-test will be applied within group If data will be not normally distributed then Mann Whittney U-test will be applied
103 Determination of Sample Size and Power Calculation
Z1-α2 Level of significance95 µ1 Expected mean change in total blood loss in Group A9380 µ2 Expected mean change in total blood loss in Group B 9598 δ1 Expected standard deviation in group A388 δ2 Expected standard deviation in group B282 Z1-β power of the study 80 sample size in a groupn 38 After adding 20 drop out 38846 in each group Total sample size will be 92 1031 Type of comparison Superiority comparison 1032 Type of configuration Parallel designs 1033 Level of significance Alpha level 95 1034 Power 08 or 80 1035 Allocation ratio 11 1036 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
1037 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 111 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
112 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
113 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
114 Management of Clinical Data The patients 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
115 Lost to Follow-up Procedures
A documented reasonable effort ie 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
116 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
117 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 121 Safety Definitions 1211 Adverse Event AE Not any 1212 Adverse Event SAE Not any 1213 Adverse Reaction Not any
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None