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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
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
Universal Trial Number (UTN)
Trial acronym
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

Study type
Description of intervention(s) / exposure

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

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.

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
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
- 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

- 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

- 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
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
Other design features
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
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
Name [1] 304614 0
Royal Brisbane and Women's Foundation
Address [1] 304614 0
Royal Brisbane and Women's Hospital (RBWH) Foundation
Butterfield Street, Herston, 4006
Country [1] 304614 0
Primary sponsor type
University of Queensland
University of Queensland Offices
Level 4, Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
QLD 4102
Secondary sponsor category [1] 305550 0
Government body
Name [1] 305550 0
Queensland Health
Address [1] 305550 0
Queensland Health Offices
Butterfield St
Herston, 4006
Country [1] 305550 0

Ethics approval
Ethics application status
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
Ethics committee country [1] 305035 0
Date submitted for ethics approval [1] 305035 0
Approval date [1] 305035 0
Ethics approval number [1] 305035 0

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

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
Phone 99050 0
+61 736468111
Fax 99050 0
Email 99050 0
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
Phone 99051 0
+61 736468111
Fax 99051 0
Email 99051 0
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
Phone 99052 0
+61 736468111
Fax 99052 0
Email 99052 0

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