The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000663358
Ethics application status
Approved
Date submitted
4/03/2017
Date registered
8/05/2017
Date last updated
16/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Tranexamic Acid in Paediatric Scoliosis Surgery (TRIPSS)
Scientific title
Randomised Trial of Low Dose versus High Dose Tranexamic Acid in Paediatric Scoliosis Surgery-effect on intraoperative blood loss and transfusion requirement
Secondary ID [1] 291281 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TRIPSS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adolescent idiopathic scoliosis 302258 0
Condition category
Condition code
Musculoskeletal 301930 301930 0 0
Other muscular and skeletal disorders
Anaesthesiology 302233 302233 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aims at determine the efficacy of Tranexamic Acid in adolescent idiopathic scoliosis surgery. A total of 160 patients are assigned into 2 groups (80 patients each)- high dose (30mg/kg loading dose over 15 minutes 30 to 60 minutes prior to surgical incision, follow by 10mg/kg/hour ) or low dose (10mg/kg loading dose over 15 minutes at 30-60minutes prior to surgical incision; follow by 1mg/kg/hour) Tranexamic Acid Regime.

Tranexamic Acid 500mg/5ml injection Bioindustria laboratorio Italiano Medinali (L.I.M) will be adminstered to the patients.

Total intraoperative Blood loss will be calculated from the cell salvage system as well as weighing the soaked sponges. This collected cell salvage blood will be re-infused to patient at the completion of surgery. For all groups,Ringer’s lactate solution will be used throughout the operation as maintenance fluid therapy and as replacement for insensible fluid loss in accordance with Holliday-Segar formula.

Should the patient developed hypotension with MAP < 60mmHg or tachycardia >20% from baseline intraoperatively, additional 5mls/kg bolus of Ringer’s lactate solution will be given to patient and can be repeated up to 4 times if necessary. However, if persistent hemodynamic instability and there is more than 20% loss of blood volume, collected cell salvage blood will be transfused back to patient immediately.

Allogenic blood would be administered when the intraoperative Hemoglobin concentration fell below 8gdl-1 despite completion of autologous blood and adequate fluid resuscitation with persistent hemodynamic instability i.e. persistent hypotension or tachycardia >20% from baseline.

Patients with postoperative Hemoglobin value of less than 8gdl-1 will also receive one unit of allogenic packed red cell transfusion.

All patients will be followed up until hospital discharge and within 30 days post-operation period.
Intervention code [1] 297318 0
Treatment: Drugs
Comparator / control treatment
1. Group A :30mg/kg loading dose over 15 minutes 30 to 60 minutes prior to surgical incision; follow by 10mg/kg/hour. (high dose)
2. Group B : 10mg/kg loading dose over 15 minutes at 30-60minutes prior to surgical incision; follow by 1mg/kg/hour. (low dose)
Control group
Dose comparison

Outcomes
Primary outcome [1] 301282 0
Mean Total blood loss
Total intraoperative blood loss will be calculated from the cell salvage system as well as weighing the soaked sponges.
Total blood loss = final volume accumulated in the reservoir (mls) - total volume of Anticoagulant Citrate Dextrose - total irrigation fluid used intraoperatively + total unfiltered blood
Timepoint [1] 301282 0
from incision until discharge from hospital
Primary outcome [2] 301283 0
Incidence of transfusion requirement
No specific tools will be used. Each subject will be followed up until discharge and event of transfusion will be recorded and analysed
Timepoint [2] 301283 0
until discharge from hospital
Secondary outcome [1] 332194 0
Perioperative changes of hemoglobin level
These samples will be delivered to our lab immediately for analysis using standard reagents.
The result will be evaluated and correlate clinically if the subject require transfusion.
Timepoint [1] 332194 0
T1: pre-operation; T2: post-operation 0 hour; T3 : post-operation 48 hour post surgery
Secondary outcome [2] 332196 0
Measurement of Plasma tranexamic acid level
Timepoint [2] 332196 0
post-operation 0 hour, 1 hour, 3 hour and 6 hour
Secondary outcome [3] 333786 0
Peri operative change of INR. Blood sample will be stored in citrate bottle and the test will be done in our hospital laboratory using standardised reagent and test.
Timepoint [3] 333786 0
T1 is pre operative, t2 is 0 hour post operative, t3 is 48hours post operative
Secondary outcome [4] 333787 0
Peri operative changes of PT. The blood sample will be stored in a citrate bottle and the test will performed in our hospital laboratory using standardised reagent
Timepoint [4] 333787 0
T1 is at preoperative, t2 is at 0 hour post operative, t3 is at 48 hours post operative
Secondary outcome [5] 333788 0
Peri operative changes in APTT.the blood sample will be stored in a citrate bottle and the test will be performed in our hospital laboratory using a standardised reagent.
Timepoint [5] 333788 0
T1 is preoperative, t2 is at 0 hour post operative, t3 is at 48 hours of post operative
Secondary outcome [6] 333791 0
Peri operative changes of fibrinogen level. The blood sample will be stored in a citrate bottle and immediately the test will be performed in our hospital laboratory using a standardised reagent
Timepoint [6] 333791 0
T1 is at preoperative, t2 is at 0 hour post operative, t3 is at 48 hours post operative

Eligibility
Key inclusion criteria
Patients who will be undergo elective single-staged idiopathic scoliosis surgery (posterior repair only)in University Malaya Medical Centre, Federal Territory, Malaysia between March 2017 and March 2018
American Society of Anesthesiologists (ASA) physical status I and II
preoperative hemoglobin level > 10 g/dL
preoperative platelet level > 150,000/L
written informed consent
Minimum age
10 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe Hematological disorder
Patients who receive anticoagulants and antiplateletswithin 14 days prior to operation
Severe cardiac disease (Aortic stenosis or cardiac ejection fraction <40%; Myocardial
infarction in the previous 6 months; myocardial ischemia on resting Electrocardiogram)
Severe pulmonary disease (FEV1 < 50% predicted, PaO2 < 9 kPa on air)
Preoperative creatinine >200 mmol/L
Serum Aspartate aminotransferase (AST)>100 IU/L

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The researcher will hand in a sealed opaque envelope containing randomisation number to the non relevant party. A non-relevant party (scrub nurse, anaesthetic assistant etc.) will prepare the assigned drug or placebo following the randomization table given to them . The operating surgeons and the anaesthetic team will not be aware of the assignment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A web-based random-number generator will be used to formulate an allocation schedule, from www.randomization.com created on 3/3/2017, 4:27:51 PM.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All data will be tabulate in a computer files and analyze using IBM SPSS software version 22. All normally-distributed numerical variables were expressed as mean +/- standard deviation and compared with the parametric One-way analysis of Variance (ANOVA) test. Data with skewed distribution were compared with Kruskal Wallis test and expressed as median [Interquartile Range]. Categorical data was presented as frequencies (percentages) and compared with the chi-square test. Level of significance is set at p < 0.05.

Sample size calculation was performed using a web-based calculator,https://www.stat.ubc.ca/~rollin/stats/ssize/n2.html, the result obtained was 80 subjects per group.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8696 0
Malaysia
State/province [1] 8696 0
Kuala Lumpur

Funding & Sponsors
Funding source category [1] 295745 0
Self funded/Unfunded
Name [1] 295745 0
Address [1] 295745 0
Country [1] 295745 0
Primary sponsor type
Individual
Name
Associate Professor Dr. Mohd Shahnaz Hasan
Address
Department of Anaesthesiology,
Level 3,
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country
Malaysia
Secondary sponsor category [1] 294587 0
Individual
Name [1] 294587 0
Dr. Ng Ching Choe
Address [1] 294587 0
Department of Anaesthesiology,
Level 3,
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country [1] 294587 0
Malaysia
Secondary sponsor category [2] 294681 0
Individual
Name [2] 294681 0
Dr Siti Nadzrah binti yunus
Address [2] 294681 0
Department of Anaesthesiology,
Level 3,
Faculty of Medicine,
University Malaya
50603 kuala Lumpur
Country [2] 294681 0
Malaysia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297044 0
Medical Research Ethics Committee, University of Malaya Medical Centre
Ethics committee address [1] 297044 0
University Malaya Medical Centre
Lembah Pantai
59100 Kuala Lumpur
Malaysia
Ethics committee country [1] 297044 0
Malaysia
Date submitted for ethics approval [1] 297044 0
04/01/2017
Approval date [1] 297044 0
18/01/2017
Ethics approval number [1] 297044 0
MEC ID : 201714-4736

Summary
Brief summary
Scoliosis surgery is often associated with substantial blood loss due to the extensive exposure and instrumentation.Despite common blood conservation strategies and improved surgical techniques used, more than half of patients underwent this procedure received blood transfusion.
Concerns of transfusion related complications have revived interest in hemostatic pharmaceuticals,
Tranexamic acid (TA) is a lysine analogue anti-fibrinolytic drug that inhibits degradation of fibrin. Recent meta-analysis has shown that TA is effective in reducing amount of blood loss and the volume of blood transfusion,
The efficacy of TA has been postulated to be dose-dependent, but there is no standard guidelines and adequate pharmacokinetic modelling study on the most appropriate dosing regimen and administration, as well as prevention of adverse events such as thromboembolism and seizure risk.

We aims to conduct this randomized study to determine the efficacy of high dose versus low dose Tranexamic Acid in surgery for adolescent idiopathic scoliosis. Primary outcome for this study is to determine the mean total blood loss and also transfusion requirement. Secondary outcome is to assess the perioperative trend of Hematological parameters and also to look at the 6-hours plasma level of Tranexamic acid post-operatively.

A total of 160 patients (80 per group) who will be undergo elective single-staged idiopathic scoliosis surgery (posterior repair only)in University Malaya Medical Centre, Federal Territory, Malaysia between March 2017 and March 2018 will be recruited in this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72794 0
A/Prof Mohd Shahnaz Hasan
Address 72794 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country 72794 0
Malaysia
Phone 72794 0
+60379493116
Fax 72794 0
Email 72794 0
shahnaz@ummc.edu.my
Contact person for public queries
Name 72795 0
Dr Ng Ching Choe
Address 72795 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country 72795 0
Malaysia
Phone 72795 0
+60379493116
Fax 72795 0
Email 72795 0
ncchoe@hotmail.com
Contact person for scientific queries
Name 72796 0
Dr Mohd Shahnaz Hasan
Address 72796 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country 72796 0
Malaysia
Phone 72796 0
+60379493116
Fax 72796 0
Email 72796 0
shahnaz@ummc.edu.my

No data has been provided for results reporting
Summary results
Not applicable