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Trial registered on ANZCTR


Registration number
ACTRN12620000537954
Ethics application status
Approved
Date submitted
7/03/2020
Date registered
1/05/2020
Date last updated
1/05/2020
Date data sharing statement initially provided
1/05/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Antibiotics versus key-hole surgery for treatment of acute appendicitis (the TRAIN trial)
Scientific title
Laparoscopic Appendicectomy versus Antibiotics for Imaging Confirmed Acute Uncomplicated Appendicitis: A Multisite Randomised Controlled Trial
Secondary ID [1] 300740 0
None
Universal Trial Number (UTN)
Trial acronym
TRAIN
Linked study record
This is a full-scale trial of the pilot study registered under ACTRN12618001229268.

Health condition
Health condition(s) or problem(s) studied:
Appendicitis 316562 0
Condition category
Condition code
Surgery 314802 314802 0 0
Surgical techniques
Infection 314803 314803 0 0
Other infectious diseases
Oral and Gastrointestinal 314968 314968 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
Antibiotics:

A minimum 48 hour duration of in-hospital, intravenous antibiotics will be given. Acceptable regimens (based on local guidelines) will be one of the following (all regimen are intravenous):
- Regimen 1: Piperacillin / Tazobactam 4.5g four times per day
- Regimen 2: Ceftriaxone 1-2g one to two times per day + Metronidazole 500mg twice or three times per day
- Regimen 3: Ampicillin/amoxicillin 2g six-hourly + Gentamicin (variable dosing as per local guideline) + Metronidazole 500mg twice or three times per day
- Regimen 4: Augmentin 1.2G 8-hourly

In the event the patient has resolving appendicitis, after 48 hours the patient will be discharged with oral antibiotics. Acceptable regimens include:
- Regimen 1: Augmentin Duo Forte 825/125mg twice per day orally
- Regimen 2: Trimethoprim/sulfamethoxazole 160/800mg twice per day + Metronidazole 400mg three times per day orally

If the patient fails to improve, an operation will be performed and this will be classed as a treatment failure as per the primary end-point.
Intervention code [1] 317062 0
Treatment: Drugs
Intervention code [2] 317401 0
Treatment: Surgery
Comparator / control treatment
Surgery (Laparoscopic Appendicectomy)
Control group
Active

Outcomes
Primary outcome [1] 323166 0
The primary outcome measure will be “treatment success” defined as successful treatment without prolonged admission or re-admission.

In the surgical arm, this will be defined as successful laparoscopic appendicectomy and discharge within one overnight stay following surgery with no complications and no re-admissions for condition or procedure related reasons within one year (e.g. pain, wound infection, complications or observation). A “treatment failure” would thus include remaining in hospital for two nights or longer, procedural complications or a visit to the General Practitioner with a wound infection or pain.

In the antibiotics arm, treatment success will be defined as avoidance of surgery or procedure and discharge within two days and no re-admissions within one year with appendicitis related symptoms. This would include re-admissions where no surgery or procedure is performed (e.g. re-presentation to the emergency department with right iliac fossa pain).

To determine the above, the patients will be physically contacted at 6 weeks and 1 year post-intervention. State-wide medical records will also be interrogated. Although the end-point will be measured at one year, contact will be made at 6 weeks to reduce the effect of recall bias (e.g. unplanned return to GP soon after discharge from hospital).
Timepoint [1] 323166 0
1 year post-randomisation (i.e. 1 year post attempt at antibiotic management or 1 year post randomisation to surgery)
Secondary outcome [1] 381020 0
Patient satisfaction scores as per the Short-Form-12 (SF12) and EuroQol-5 Dimension 5 Level (EQ-5D-5L). This will be performed via a phone survey.
Timepoint [1] 381020 0
6 weeks and 1 year post randomisation.
Secondary outcome [2] 381731 0
Complications and morbidity as per Clavien-Dindo Classification, This will be determined through phone survey and interrogation of medical records.
Timepoint [2] 381731 0
6 weeks and 1 year post randomisation
Secondary outcome [3] 381732 0
Days off work, as per patient phone call.
Timepoint [3] 381732 0
At 6 weeks post randomisation.

Eligibility
Key inclusion criteria
- Uncomplicated acute appendicitis as deemed by reporting radiologist at time of admission
- Clinical diagnosis of appendicitis as per treating physician
- Age 18 to 50, both males and females
- Able to speak English and consent to follow up
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical
- Age < 18 or > 50
- Severe sepsis / septic shock / medically unstable as per treating physician
- Severe peritonitis (as per treating physician)
- Abdominal surgery within last month
- Received antibiotics within last week
- Allergy to all study antibiotics

Co-morbidities
- Pregnancy
- Complex diabetes: requiring any medication (e.g. metformin, insulin), ketoacidosis or coma
- Immunodeficiency
- Ischaemic heart disease, Congestive heart failure, Congenital heart disease
- Cardiac surgery or coronary stents
- Takin aspirin, antiplatelet, anticoagulant medications
- History of bleeding disorders
- History of chronic liver disease, cirrhosis, liver failure
- Chronic renal insufficiency (eGFR < 40), haemodialysis, peritoneal dialysis, plasmapheresis
- Concurrent severe illness requiring hospitalization
- Other infection requiring antibiotic treatment
- Intravenous drug use (ever)
- Cognitive impairment, intellectual disability, severe mental illness
- Previous colonic or small bowel surgery
- Any active malignancy apart from non-metastatic skin cancer

Logistical
- Inability/unwilling to return for follow up
- Inability to provided written informed consent
- Non-English speaker

Radiological Exclusion Criteria
- CT / USS evidence of complicated appendicitis (phlegmon, abscess, perforation)
- Presence of faecolith
- Any radiological suspicion for alternative diagnosis or malignancy

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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 in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 16083 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 16084 0
Caboolture Hospital - Caboolture
Recruitment hospital [3] 16085 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 16086 0
Cairns Base Hospital - Cairns
Recruitment hospital [5] 16087 0
The Townsville Hospital - Douglas
Recruitment hospital [6] 16088 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment hospital [7] 16089 0
Logan Hospital - Meadowbrook
Recruitment hospital [8] 16090 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 16091 0
Toowoomba Hospital - Toowoomba
Recruitment postcode(s) [1] 29595 0
4006 - Herston
Recruitment postcode(s) [2] 29602 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 29600 0
4108 - Coopers Plains
Recruitment postcode(s) [4] 29601 0
4131 - Meadowbrook
Recruitment postcode(s) [5] 29603 0
4350 - Toowoomba
Recruitment postcode(s) [6] 29596 0
4510 - Caboolture
Recruitment postcode(s) [7] 29597 0
4575 - Birtinya
Recruitment postcode(s) [8] 29599 0
4814 - Douglas
Recruitment postcode(s) [9] 29598 0
4870 - Cairns

Funding & Sponsors
Funding source category [1] 304614 0
Charities/Societies/Foundations
Name [1] 304614 0
Royal Brisbane and Women's Foundation
Address [1] 304614 0
Royal Brisbane and Women's Hospital (RBWH) Foundation
RBWH
Butterfield Street, Herston, 4006
QLD
Country [1] 304614 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
University of Queensland Offices
Level 4, Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
QLD 4102
Country
Australia
Secondary sponsor category [1] 305550 0
Government body
Name [1] 305550 0
Queensland Health
Address [1] 305550 0
Queensland Health Offices
RBWH
Butterfield St
Herston, 4006
QLD
Country [1] 305550 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305035 0
Townsville Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 305035 0
Townsville Hospital and Health Service Human Research Ethics Committee
Townsville Hospital
100 Angus Smith Drive
Douglas, 4814
QLD
Ethics committee country [1] 305035 0
Australia
Date submitted for ethics approval [1] 305035 0
25/11/2019
Approval date [1] 305035 0
19/12/2019
Ethics approval number [1] 305035 0
59863

Summary
Brief summary
The traditional treatment for appendicitis is an operation but this has been challenged by other studies in recent years: we will treat some patients with antibiotics alone and see if their appendicitis resolves without an operation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99050 0
Dr Andrew Maurice
Address 99050 0
University of Queensland Offices
Level 4, Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
QLD, 4102
Country 99050 0
Australia
Phone 99050 0
+61 736468111
Fax 99050 0
Email 99050 0
andrew.maurice@uqconnect.edu.au
Contact person for public queries
Name 99051 0
Dr Andrew Maurice
Address 99051 0
University of Queensland Offices
Level 4, Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
QLD, 4102
Country 99051 0
Australia
Phone 99051 0
+61 736468111
Fax 99051 0
Email 99051 0
andrew.maurice@uqconnect.edu.au
Contact person for scientific queries
Name 99052 0
Dr Andrew Maurice
Address 99052 0
University of Queensland Offices
Level 4, Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
QLD, 4102
Country 99052 0
Australia
Phone 99052 0
+61 736468111
Fax 99052 0
Email 99052 0
andrew.maurice@uqconnect.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results