Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000109505
Ethics application status
Approved
Date submitted
30/07/2023
Date registered
8/02/2024
Date last updated
8/02/2024
Date data sharing statement initially provided
8/02/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Bedside Ultrasound study for appendicitis and its utility in the emergency department (Australian ED setting)
Scientific title
Diagnostic Accuracy of Point of Care Ultrasound (POCUS) for appendicitis in the Paediatric Population in an Australian ED Setting.
Secondary ID [1] 310239 0
nil known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Appendicitis 330933 0
Condition category
Condition code
Emergency medicine 328043 328043 0 0
Other emergency care
Oral and Gastrointestinal 328881 328881 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be identified by ED doctor's (Consultants, Registrars and RMO) on initial clinical exam if they meet the inclusion criteria of the study. Patients would only be approached for POCUS study when POCUS-certified clinicians are on shift. Initial doctor seeing the patient (intern, Resident Medical Officer (RMO), Registrar, other non-trained Consultants) would start off the data collection form based on history and clinical exam. Information about the participation information would be handed out at this point to give participants an opportunity to read and understand. Analgesia would be ensured prior to scan,

POCUS-certified physician will then approach the patient or their guardian/caregiver/parent to discuss potential study involvement and to seek verbal consent. There are two sets of clinicians performing the bedside ultrasound: accredited and nonaccredited. The accredited clinicians would perform bedside scans and if patients are positive for appendicitis, they would be referred to Surgeons directly. If the results are equivocal (meaning that appendix is not fully visualised) or negative, then they would arrange a subsequent formal ultrasound.

Non accredited clinicians performing POCUS will only perform bedside POCUS after verbal consent and all the bedside scans is followed up by formal scans. If at any point, the patient is uncomfortable and does not wish to have POCUS performed, the bedside POCUS exam would stop, and the patient’s concerns will be addressed.

POCUS findings will be documented in the proforma. All Bedside scans will be done within 30min and opportunistically.

Comparison would be made with subsequent RADUS scans (reported by the consultant Radiologist). The RADUS will be assessed from the Picture Archiving and Communications system (PACS) and findings would be recorded as either appendicitis, not appendicitis or equivocal.
Additional data collected about the ED visit will include laboratory findings ..

If appendicectomy is done, then the histo-pathological findings will be searched from the OASICS software and compared to both scans performed (in some cases with 1 bedside scan performed (for accredited clinicians))

POCUS performed positive scans would be compared with histopathology-proven appendicitis to deem true positive.

The only key between bedside POCUS and RADUS would be the level of experience or skills, more detailed exam (by RADUS) as they would be looking for other causes of abdominal pain if not appendicitis and the quality of the ultrasound machines.

All bedside scans would be done within 30 mins. Timings would be recorded. It would be done opportunistically while patients are waiting for formal scans.

- In terms of training; All clinicians would get 1 hour of didactic teaching by an experienced sonographer 4 weeks before commencement. A practical session would follow with demonstration of POCUS technique on healthy volunteer patients. The first 10 scans done by non-accredited clinicians would be supervised by accredited clinicians in ED and data collected would be under the names of the accredited clinician's name. After the 10 initial scans supervised, the non-accredited clinicians would then perform scans individually.
- Follow-up would be done for all patients who have had negative or equivocal ultrasound scan results by both physician and radiographer performed. They would be followed up via a text message in two weeks to check if they represented with abdominal pain again to any hospital after the initial hospital visit.

Intervention code [1] 326627 0
Early detection / Screening
Intervention code [2] 327488 0
Diagnosis / Prognosis
Comparator / control treatment
Bedside Clinician performed ultrasound compared to formal radiographer performed scan. Formal scans would be performed by sonographers and read by consultant Radiologist.

Time to formal scan varies depending on the timing of the day. During day time , this can be 1-4 hours. Overnight , there are usually no sonographers around and patients are then booked for “next day ultrasound”. If patient is clinically not well , sometimes sonographers are called in overnight.
Control group
Active

Outcomes
Primary outcome [1] 336689 0
To determine the diagnostic accuracy of POCUS for appendicitis when performed by ED clinicians. Positive POCUS findings will be compared with the histopathology.
Timepoint [1] 336689 0
This study would be carried out from August 2023 to May 2024.
RADUS can take up to 1-4 hours if performed during day time working hours. There are no sonographers available on site after hours, therefore, for some patients the formal RADUS would be arranged as "next day ultrasound" if clinically stable and presentation has been after hours.
Secondary outcome [1] 424895 0
Proportion of equivocal diagnoses of POCUS as determined by physician
Timepoint [1] 424895 0
This will be assessed during data analysis post study.

Eligibility
Key inclusion criteria
-Children between the age 5 to 18 years
-< 5 days duration (120 hours) of pain
-Appendicitis is a differential diagnosis
Minimum age
5 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Pain >120 hours duration
- Previous bowel surgery, IBD, chronic pancreatitis, CF, sickle cell disease??
-Medical condition preventing the ability to obtain accurate history –nonverbal?
- Language barrier
-Transplant patients
-Abdominal trauma within two weeks
-Hemodynamic instability requiring resuscitation
-Pregnancy
- Testicular pain

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
not a RCT
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NOT A RCT
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Prospective study
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This study will be a single-centre convenience sample prospective study for over one year at an academic tertiary Paediatric Hospital.

POCUS Appendicitis Study: Analysis Plan

Primary Outcome: The primary aim of the study is to determine the accuracy of POCUS, performed in the paediatric ED by ED physicians, for diagnosis of appendicitis. The study population will consist of patients 5-18 years old presenting to the WCH ED with suspicion of appendicitis. Study will over a 9-month period, with POCUS performed by 7 different ED physicians with differing levels of experience. Thus, the primary interest are overall measures of diagnostic accuracy of POCUS when performed in the ED setting on children 5-18 years old, with pain <120 hours 'duration, in whom appendicitis is a differential diagnosis.

The measures of diagnostic accuracy to be estimated are:
Sensitivity: proportion of appendicitis cases which are correctly diagnosed via POCUS. For this measure, an equivocal diagnosis will be treated as not correctly diagnosed; i.e. the POCUS diagnosis will be dichotomized as ‘diagnosed as appendicitis’ versus ‘not diagnosed as appendicitis’.
Specificity: proportion of non-appendicitis cases which are correctly diagnosed via POCUS. For this measure, an equivocal diagnosis will be treated as not correctly diagnosed; i.e. the POCUS diagnosis will be dichotomized as ‘diagnosed as negative for appendicitis’ versus ‘not diagnosed as negative for appendicitis’.
Positive Predictive Value: proportion of patients diagnosed as appendicitis via POCUS who have appendicitis. Equivocal diagnoses will be classified as ‘not diagnosed as appendicitis’ as for sensitivity above.
Negative Predictive Value: proportion of patients diagnosed as negative for appendicitis via POCUS who actually do not have appendicitis. Equivocal diagnoses will be classified as ‘not diagnosed as equivocal for appendicitis’ as for specificity above.

Note that in similar studies of diagnostic accuracy of POCUS, equivocal or inconclusive diagnoses have been classified as ‘negative’ (i.e. not appendicitis) for all performance measures; however the current plan is to classify equivocal/inconclusive diagnoses as ‘not diagnosed as appendicitis’ for sensitivity and PPV, and ‘not diagnosed as negative for appendicitis’ for specificity and NPV. This is because an equivocal diagnosis is strictly speaking neither positive nor negative, and patients with this diagnosis would in practice be followed up with further investigation rather than being treated as definitively having appendicitis or definitively not having appendicitis. In fact, the performance of POCUS in relation to correctly ruling out appendicitis is not symmetrical to its performance for correctly identifying appendicitis, and these two types of accuracy should be considered separately. For this reason, likelihood ratios have not been included in the list of performance measures, as they combine estimates of sensitivity and specificity (positive likelihood ratio is sensitivity/(1-specificity) and negative likelihood ratio is (1-sensitivity)/specificity ); in this context they are of less relevance as they would require equivocal diagnoses to be interpreted as either positive or negative diagnoses.

Method of analysis: a logistic regression model will be fitted in which the predictor is POCUS diagnosis (yes, no, or equivocal diagnosis). The probability of appendicitis corresponding to each category will be estimated and the measures listed above calculated. 95% Confidence Intervals for each of the measures will be calculated using the exact (Clopper-Pearson) method.

Decision curves will be used to show the Net Benefit of using POCUS for (a) ruling out appendicitis, and (b) diagnosing appendicitis, versus further investigation of all patients.

Secondary Outcomes

1. Variation in diagnostic accuracy by physician experience

The performance measures listed above will be assessed for variation according to level of ED Physician experience. Sensitivity, specificity, PPV and NPV for 3-month increments of physician experience will be calculated as defined above using random effects to account for correlation (and potentially heterogeneity of time effect) due to repeated values for each ED physician.

If sample size permits, models may also be fitted separately for each physician to estimate the change in probabilities of appendicitis corresponding to each diagnostic category (yes, no, equivocal) over time.

Decision curves as described above will be produced for different levels of physician experience, to assess the Net Benefit of using POCUS performed by less or more experienced physicians.

2. Proportion of equivocal diagnoses by physician experience

The proportion of equivocal diagnoses within a 3-month period will be modelled as a function of physician experience (categorised in 3-month increments), to estimate the change in proportion of equivocal diagnoses with increasing experience. As with variation in diagnostic accuracy, random effects will be used to account for correlation due to the same ED physicians being repeatedly measured over time.

3. Increase in predictive performance with addition of POCUS to risk prediction tools

POCUS diagnosis will be added to risk prediction models (utilising existing tools, i.e. pARC / PAS / Alvarado score) to assess whether this results in an improvement in model performance. Model performance will be assessed using calibration curves (actual proportion of appendicitis cases within categories of predicted risk), Area Under the ROC Curve, and the measures above. Sensitivity and specificity will be calculated against a threshold determined by a fixed false negative rate (the maximum clinically acceptable rate of false negative diagnoses). Comparison between models with and without POCUS will be undertaken using measures of model fit and area under the ROC curve, as well as descriptive comparison of other model measures. Bootstrap validation will be carried out to determine the extent of optimism in estimated model performance due to overfitting.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
13/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
60
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 25291 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 40964 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 314447 0
Hospital
Name [1] 314447 0
Kind in support - Women's and Children Hospital
Country [1] 314447 0
Australia
Primary sponsor type
Hospital
Name
Women's and Children Hospital Network (WCHN)
Address
72 King William Rd,North Adelaide,SA 5006 Australia
Country
Australia
Secondary sponsor category [1] 316668 0
None
Name [1] 316668 0
Address [1] 316668 0
Country [1] 316668 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313487 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 313487 0
Research GEMS 72 King William Rd North Adelaide SA 5006 Australia
Ethics committee country [1] 313487 0
Australia
Date submitted for ethics approval [1] 313487 0
12/04/2023
Approval date [1] 313487 0
15/06/2023
Ethics approval number [1] 313487 0
2023/HRE00088

Summary
Brief summary
The primary aim of the study is to determine the accuracy of POCUS, performed in the paediatric ED by ED physicians, for diagnosis of appendicitis. The study population will consist of patients 5-18 years old presenting to the WCH ED with suspicion of appendicitis over a 9 month period, with POCUS performed by 7 different ED physicians with differing levels of experience. Thus the primary interest are overall measures of diagnostic accuracy of POCUS when performed in the ED setting with formal scans.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128342 0
Dr Nandini Sami
Address 128342 0
Paediatric Emergency Department Women's and Children Hospital 72 King William RD, North Adelaide, SA 5006, Australia
Country 128342 0
Australia
Phone 128342 0
+61 492803673
Fax 128342 0
Email 128342 0
nandini.sami@sa.gov.au
Contact person for public queries
Name 128343 0
Dr Nandini Sami
Address 128343 0
Paediatric Emergency Department, Women's and Children Hospital, 72 King William RD, North Adelaide, SA 5006, Australia
Country 128343 0
Australia
Phone 128343 0
+61 492803673
Fax 128343 0
Email 128343 0
nandini.sami@sa.gov.au
Contact person for scientific queries
Name 128344 0
Dr Nandini Sami
Address 128344 0
Paediatric Emergency Department, Women's and Children Hospital, 72 King William RD, North Adelaide, SA 5006, Australia
Country 128344 0
Australia
Phone 128344 0
+61 492803673
Fax 128344 0
Email 128344 0
nandini.sami@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
all data will be pooled


What supporting documents are/will be available?




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.