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Trial registered on ANZCTR


Registration number
ACTRN12621000107820
Ethics application status
Approved
Date submitted
17/09/2020
Date registered
3/02/2021
Date last updated
27/04/2023
Date data sharing statement initially provided
3/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
STOP : Study of Tranexamic acid On Post Tonsillectomy haemorrhage
Scientific title
STOP : Study of Tranexamic acid On Post Tonsillectomy haemorrhage in children and adolescents
Secondary ID [1] 302342 0
Therapeutic Goods Administration, Australian Government Department of Health; CT-2022-CTN-00420-1
Universal Trial Number (UTN)
Trial acronym
STOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary post tonsillectomy haemorrhage 319115 0
Condition category
Condition code
Emergency medicine 317076 317076 0 0
Other emergency care
Surgery 317491 317491 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of nebulised tranexamic acid (nTXA) for patients (aged 3-16 yrs) presenting to the emergency department (ED) with a case of secondary post tonsillectomy haemorrhage (sPTH). The solution for injection form of tranexamic acid (100mg/ml) will be used and administered via a nebuliser. The dose will be 250 mg for patients weighing less than or equal to 25 kg and 500 mg for patients weighing more than 25 kg. The nebulised dose of TXA will be given in lieu of a single intravenous dose of TXA which is our current standard management for sPTH in the ED at the study site. Adherence to the intervention will monitored in a number of ways. The allocated study pack will be bundled with the study data collection form (CF). This will provide clear guidance on which form of TXA is to be given and will provide a source of documentation. Medical records including ED medical notes, ED nursing notes and medication charts will also provide sources to verify method and dose of TXA administration.
Intervention code [1] 318634 0
Treatment: Drugs
Comparator / control treatment
The control group or arm will be patients who receive a single dose (10 mg/kg) of intravenous tranexamic acid (IV TXA) which forms our current standard management of this condition in our emergency department.
Control group
Active

Outcomes
Primary outcome [1] 325166 0
The primary outcome measure will be a change in bleeding grade, according to a modified version of the Stammberger classification of sPTH, measure 15 minutes after commencement of TXA treatment.

Timepoint [1] 325166 0
Time Zero minutes (T0) - baseline bleeding grade using the modified Stammberger classification of sPTH taken at time 0 minutes during initial ED doctor assessment. Time Fifteen minutes (T15) - follow-up bleeding grade according to a modified Stammberger classification of sPTH, taken at time 15 minutes from the initial ED doctor assessment
Secondary outcome [1] 387054 0
Time from initial ED assessment to commencement of tranexamic acid therapy (nTXA or IV TXA). This time will be obtained from the study data collection form (CF). The electronic Emergency Department patient information system (EDIS) and hospital medication charts will provide an additional sources of verification.
Timepoint [1] 387054 0
At any time following initial ED doctor assessment.
Secondary outcome [2] 387057 0
Rescue therapy rates for those randomised to nTXA; defined as receiving a dose of IV TXA at any stage within the first 2 hours. The indications to give this 'rescue' IV TXA are clearly defined within the protocol. This outcome will be assessed using data from the study CF. All cases allocated to the nTXA arm will be additionally analysed by review of the patient medical record and medication chart to determine whether any IV TXA was administered within the first two hours of presentation to ED.
Timepoint [2] 387057 0
Within the first 2 hours of treatment within the ED.
Secondary outcome [3] 387059 0
Total volume per kg of intravenous fluid therapy received in the first hour in the ED. This outcome will be assessed by examining patient intravenous fluid charts and patient medical records.
Timepoint [3] 387059 0
Within the first hour of treatment within the ED.
Secondary outcome [4] 387060 0
Patient Full Blood Examination (FBE), taken at the time of patient presenting to ED with sPTH . We intend to examine baseline haemoglobin.
Timepoint [4] 387060 0
FBE taken from patient during the ED episode for sPTH.
Secondary outcome [5] 387061 0
Blood product administration rates during the hospital admission. This outcome will be assessed by examination of patient medical records,including medical and nursing notes, blood product forms and intravenous fluid charts. Further analysis will be performed by cross checking patient hospital numbers for supply of blood products with our transfusion medicine laboratory.
Timepoint [5] 387061 0
At any time of the patient's admission to hospital with sPTH.
Secondary outcome [6] 387062 0
Hospital Length of Stay (LOS) in hours. This will be obtained from our hospital business intelligence unit. Further analysis will obtained from the hospital electronic patient information system if required.
Timepoint [6] 387062 0
Determined after the patient's hospital admission is complete.
Secondary outcome [7] 387063 0
Return to theatre (RTT) rates for control of sPTH. This will be determined from the patient medical record including medical notes, nursing notes and theatre records and the electronic discharge summary. Further analysis will obtained from the hospital business intelligence unit and the hospital patient electronic information system using the patient hospital number.
Timepoint [7] 387063 0
At any time of the patient's admission to hospital with sPTH.
Secondary outcome [8] 387064 0
ICU admission rate. This will be obtained from the patient medical record including medical records and nursing records and the electronic discharge summary.
Timepoint [8] 387064 0
At any time of the patient's admission to hospital with sPTH.
Secondary outcome [9] 387065 0
Determination of complication rates in relation to TXA administration including: Bronchospasm occurring after treatment with a nebulised dose of TXA. This will be determined from the study CF and by examination of the patient medical record including medical and nursing notes plus medication chart for administration of bronchodilators during the time in ED.
Timepoint [9] 387065 0
At any time of the patient's treatment within the ED.
Secondary outcome [10] 387066 0
Determination of complication rates in relation to TXA administration including:
Requirement of treatment for an allergic reaction. This will be determined from the study CF and by examination of the patient medical record including medical and nursing notes plus medication chart for administration of adrenaline, steroids or anithistamines during the time in ED.
Timepoint [10] 387066 0
At any time of the patient's treatment within the ED.
Secondary outcome [11] 387067 0
Determination of complication rates in relation to TXA administration including: Significant nausea, vomiting or abdominal pain during the hospital admission. This will be determined from the study CF and by examination of the patient medical record including medical and nursing notes, electronic discharge summary plus the medication chart for administration of repeated doses of antiemetics. This information will also be recorded as part of the Day 7 follow up phone call or sms to the parent.
Timepoint [11] 387067 0
At any time of the patient's admission to hospital with sPTH.
Secondary outcome [12] 387068 0
Determination of complication rates in relation to TXA administration including: Unexpected thrombotic events, renal impairment, or seizures within the first 7 days of presentation. This will be determined from the study CF and by examination of the patient medical record including medical and nursing notes, electronic discharge summary plus the inspection of medication chart for doses of seizure management medications or anticoagulants. The hospital electronic pathology system will be used to seek any creatinine values that fall into the abnormal range during the hospital stay. This information will also be recorded as part of the Day 7 follow up phone call or sms to the parent
Timepoint [12] 387068 0
At any time within the first 7 days of the patient's presentation to the ED with sPTH.
Secondary outcome [13] 388300 0
Coagulation Profile (CP) comprising of INR, APTT and fibrinogen levels.
Timepoint [13] 388300 0
Blood results taken at the time of patient presenting to ED with sPTH and any further subsequently during the hospital stay. This outcome will be assessed using the hospital electronic pathology results system.
Secondary outcome [14] 388301 0
Von Willebrand Factor (VWF) assay.
Timepoint [14] 388301 0
Blood results taken at the time of patient presenting to ED with sPTH. This outcome will be assessed using the hospital electronic pathology results system.
Secondary outcome [15] 406448 0
Nil assistance required to complete nebulised TXA. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [15] 406448 0
After completion of the nebuliser
Secondary outcome [16] 406449 0
Minor assistance required to complete nebuliser; including positional adjustments and corrections. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [16] 406449 0
After completion of the nebuliser
Secondary outcome [17] 406450 0
Extensive assistance required to complete nebuliser; including holding the mask in place by force. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [17] 406450 0
After completion of the nebuliser.
Secondary outcome [18] 406451 0
Failure to complete the nebuliser. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [18] 406451 0
After the nebuliser dose has completed through the nebuliser device.
Secondary outcome [19] 406452 0
Coughing or spitting blood during nTXA or IV TXA treatment. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [19] 406452 0
After completion of the TXA treatment.
Secondary outcome [20] 406453 0
New onset cough during or immediately after the nTXA or IV TXA treatment. This specific information will be collected in real time by the treating ED doctor on the study data collection form.
Timepoint [20] 406453 0
After completion of the nTXA or IV TXA treatment.

Eligibility
Key inclusion criteria
Patients age 3-16 years presenting to a tertiary paediatric emergency department within the hours of 0600-2400 with secondary post tonsillectomy haemorrhage (sPTH). sPTH is defined as bleeding onset more than 24hrs after initial tonsillectomy.
Minimum age
3 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Initial Exclusion Criteria;
Any sPTH patient with an obvious Grade 4 bleed.
Any sPTH patient that appears pale, subdued or unwell looking.
Any sPTH patient with a HR or BP giving an early warning score of 3 on the local institution's Paediatric Acute Recognition and Response Observation Tool at the time of ED presentation.

Further Exclusion Criteria;
Any patient presenting with sPTH who has already received IV TXA or oral TXA as part of their treatment for that episode of sPTH. This may occur if they have transferred from a peripheral ED.

Patients with a known allergy or contraindication to TXA.

Patients with a history of severe asthma defined as previous ICU admission for asthma.

Patients with a prothrombotic condition including thromboembolism, deep venous thrombosis, stroke, or Kawasaki’s disease.

Patients with known renal impairment.

Patients with a seizure disorder

Patients with a known bleeding disorder

Patients who have previously been enrolled in this study

Patients with parents or carers who are judged to have a limited understanding of English and therefore, will not be able to participate in the deferred consent process.


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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent statistician or pharmacist will generate a randomisation schedule using variable block sizes. Patients will be block randomised in a 1:1 ratio to one of the two treatment groups: nTXA or standard IV TXA therapy.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2022
Actual
22/10/2022
Date of last participant enrolment
Anticipated
1/04/2024
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
70
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 31300 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 306771 0
Hospital
Name [1] 306771 0
Perth Children's Hospital
Country [1] 306771 0
Australia
Primary sponsor type
Hospital
Name
Perth Children's Hospital
Address
15 Hospital Avenue
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 307324 0
None
Name [1] 307324 0
Address [1] 307324 0
Country [1] 307324 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306937 0
Child and Adolescent Health Service HREC
Ethics committee address [1] 306937 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Ethics committee country [1] 306937 0
Australia
Date submitted for ethics approval [1] 306937 0
20/10/2020
Approval date [1] 306937 0
18/11/2021
Ethics approval number [1] 306937 0

Summary
Brief summary
STOP is intended to be a small pilot study conducted in a specialised paediatric emergency department (ED) examining the effect of giving the medication tranexamic acid or 'TXA' via a nebuliser on children aged 3-16y ears who come to the ED with throat bleeding after tonsillectomy surgery. We intend to study whether nebulised TXA is a safe and effective alternative to intravenous TXA, which is currently part of the standard treatment for this condition in the institution involved. Each child presenting to our ED with bleeding following tonsillectomy surgery will be screened for suitability, considered for enrolment and approached for consent to participate. Half of the patients will be allocated to a single initial dose of nebulised TXA and half will be allocated the standard single dose intravenous TXA treatment. We will grade the severity of bleeding from the throat on each patient firstly on their arrival to the ED and again 15 minutes after the TXA has been administered. We will also capture data concerning the timing of treatment, the acceptability and tolerance to nebulised TXA for this condition and information regarding the patient's episode of hospital care. The results will help us understand whether nebulised TXA is tolerated, easy to administer, its safety profile and its impact on post tonsillectomy bleeding in comparison to IV TXA treatment. We will also seek to establish if there is any evident differences in subsequent hospital stay and medium term adverse effects.
Trial website
Trial related presentations / publications

Public notes

Contacts
Principal investigator
Name 105510 0
Dr Kate Wheadon
Address 105510 0
Emergency Department
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 105510 0
Australia
Phone 105510 0
+61 8 64562222
Fax 105510 0
Email 105510 0
[email protected]
Contact person for public queries
Name 105511 0
Sharon O'Brien
Address 105511 0
Emergency Department
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 105511 0
Australia
Phone 105511 0
+61 8 64562222
Fax 105511 0
Email 105511 0
sharon.o'[email protected]
Contact person for scientific queries
Name 105512 0
Kate Wheadon
Address 105512 0
Emergency Department
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 105512 0
Australia
Phone 105512 0
+61 8 64562222
Fax 105512 0
Email 105512 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality. Small intra-departmental pilot trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.