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Trial registered on ANZCTR


Registration number
ACTRN12618001229268
Ethics application status
Approved
Date submitted
15/06/2018
Date registered
23/07/2018
Date last updated
30/07/2019
Date data sharing statement initially provided
30/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Antibiotics versus key-hole surgery for successful treatment of acute appendicitis
Scientific title
Laparoscopic Appendicectomy versus Antibiotics for Resolution of Radiologically Confirmed Acute Uncomplicated Appendicitis: A Multi-Centre Randomised Pilot Tria
Secondary ID [1] 295217 0
None
Universal Trial Number (UTN)
Trial acronym
PLAPPY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Appendicitis 308369 0
Condition category
Condition code
Surgery 307359 307359 0 0
Surgical techniques
Oral and Gastrointestinal 307555 307555 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:

All patients will receive intravenous ceftriaxone 1g twice per day and intravenous metronidazole 500mg twice per day, in keeping with the Australian Therapeutic Guidelines for severe intra-abdominal infection secondary to perforated viscus. The patients would be re-evaluated within 12 to 24 hours of receiving the antibiotics and monitored at least daily. At least daily blood test will be performed.

If the patient has not met any failure criteria after 48 hours of treatment with IV antibiotics (i.e. at least 2 doses of ceftriaxone and 4 doses of metronidazole), the patient will be transitioned to a 5 day course of oral Augmentin DuoForte (amoxicillin 875mg + clavulanic acid 125mg) twice per day as an inpatient or an outpatient.

A patient who is hypersensitive or has a documented adverse drug reaction to the study medications will not be recruited for the study.

Failure of antibiotic therapy will be at the discretion of the treating physician. The treating physician will have to document the reason for failure: persistent tachycardia, persistent fever, worsening laboratory results (including white blood cell count or CRP), non-resolution or worsening of pain, signs of peritonitis, signs of shock, patient preference to proceed with surgery or other.
Intervention code [1] 301554 0
Treatment: Drugs
Intervention code [2] 301696 0
Treatment: Surgery
Comparator / control treatment
Laparoscopic Appendicectomy: this "key hole" operation is the standard treatment for those who present with appendicitis in Australia
Control group
Active

Outcomes
Primary outcome [1] 306325 0
Freedom from appendicectomy within 6 weeks (antibiotic group). The patient will be reviewed in the outpatient department to ascertain if surgery has been required. If the patient fails to attend, they will be contacted by phone. If the investigators are unable to contact the patient, their state-wide electronic health record will be interrogated ("The Viewer").
Timepoint [1] 306325 0
6 weeks post discharge from hospital.
Primary outcome [2] 306326 0
Successful appendicectomy (surgical group); that is successful appendicectomy with laparoscopic surgery and discharge as per the medical record and operation report. If open surgery, repeat surgery, interventional radiology procedures or prolonged antibiotics are required (e.g. for abscess), surgery will be deemed a failure.
Timepoint [2] 306326 0
Successful laparoscopic surgery and discharge without re-admission for further surgery or antibiotics 6 weeks following discharge.
Secondary outcome [1] 348189 0
Days off work as per patient reported survey at outpatients appointment 6 weeks following discharge. If patients fail to attend, they will be contacted by phone.
Timepoint [1] 348189 0
6 weeks following discharge.
Secondary outcome [2] 348190 0
Pain score as per 10-point VAS scale.
Timepoint [2] 348190 0
6 weeks post discharge from hospital at outpatient follow up. If patients fail to attend, they will be contacted by phone.
Secondary outcome [3] 348191 0
Requirement for opioid analgesia on discharge as per hospital medical record and requirement for opioid analgesia following discharge as per outpatient appointment 6 weeks following discharge from hospital.
Timepoint [3] 348191 0
6 weeks post discharge from hospital.
Secondary outcome [4] 348192 0
Surgical complications (if surgery undertaken) as per medical record.
Timepoint [4] 348192 0
From admission until 6 weeks post discharge from hospital. This would encompass re-admission and further treatment including wound infection, need for radiological or surgical re-intervention.
Secondary outcome [5] 348193 0
Hospital length of stay as per hospital record.
Timepoint [5] 348193 0
Hospital inpatient length of stay until 6 weeks post initial discharge: this will thus include re-admissions.
Secondary outcome [6] 348194 0
Medical complications including drug side effects (especially those due to antibiotics), abscess or phlegmon formation, perforation as per the hospital medical records.
Timepoint [6] 348194 0
From admission until 6 weeks following discharge.
Secondary outcome [7] 348195 0
Patient Satisfaction (questionnaire designed specifically for this study).
Timepoint [7] 348195 0
Questionnaire performed at 6 week outpatient appointment following inpatient episode.

Eligibility
Key inclusion criteria
1. Clinical diagnosis of appendicitis as per treating physician.
2. Radiological evidence of appendicitis on Ultrasound or Computed Tomography scan.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical Exclusion Criteria:
Age < 18 or > 50
Severe sepsis / septic shock
Peritonitis
Abdominal surgery within last month
Received antibiotics within last week
Allergy to study medications (i.e. antibiotic regimen, paracetamol)

Comorbidity exclusion criteria
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 Exclusion Criteria
Inability/unwilling to return for follow up
Inability to provided written informed consent
Non-English speaker
Aboriginal and Torres Strait Islander heritage

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation with 3:1 allocation (3 antibiotics to 1 surgery) using statistical software STATA.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is a pilot trial and by definition will be under-powered. Non-quantitative descriptive statistics will be used only.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2018
Actual
1/12/2018
Date of last participant enrolment
Anticipated
1/12/2019
Actual
Date of last data collection
Anticipated
21/01/2020
Actual
Sample size
Target
40
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14351 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 14352 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 14353 0
The Townsville Hospital - Douglas
Recruitment postcode(s) [1] 27354 0
4029 - Herston
Recruitment postcode(s) [2] 27355 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 27356 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 299805 0
Charities/Societies/Foundations
Name [1] 299805 0
Townsville Hospital Study, Education and Research Trust Account (SERTA)
Country [1] 299805 0
Australia
Primary sponsor type
Hospital
Name
Townsville Hospital
Address
Townsville Hospital
100 Angus Smith Drive, Douglas
Townsville, QLD, 4814
Country
Australia
Secondary sponsor category [1] 299154 0
None
Name [1] 299154 0
Address [1] 299154 0
Country [1] 299154 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300687 0
Townsville Hospital Human Research and Ethics Committee
Ethics committee address [1] 300687 0
Human Research and Ethics Committee
Townsville Hospital
100 Angus Smith Drive, Douglas
Townsville, QLD, 4814
Ethics committee country [1] 300687 0
Australia
Date submitted for ethics approval [1] 300687 0
25/06/2018
Approval date [1] 300687 0
27/07/2018
Ethics approval number [1] 300687 0

Summary
Brief summary
Appendicitis has usually been treated with an operation (i.e. appendicectomy) for the last 125 years however recent studies have suggested antibiotics may be an effective treatment strategy in a subset of patients. While many recent studies have examined this, only one large rigorous clinical trial has been performed (the 2015 APPAC trial), itself with multiple caveats which limit generalizability to the Australian population. Another large trial, the CODA trial in the United States, also is underway however it too will be difficult to generalise this trial to the Australian setting.

We aim to conduct a pilot trial to assess the feasibility and acceptability of a treatment protocol designed to compare antibiotics with laparoscopic appendicectomy for the treatment of mild acute uncomplicated appendicitis.

The ultimate goal of this trial would be to perform a large, multi-centre trial in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84478 0
Dr Andrew Maurice
Address 84478 0
Department of General Surgery
Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville, QLD, 4814
Country 84478 0
Australia
Phone 84478 0
+61744331111
Fax 84478 0
Email 84478 0
andrew.maurice@uqconnect.edu.au
Contact person for public queries
Name 84479 0
Dr Andrew Maurice
Address 84479 0
Department of General Surgery
Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville, QLD, 4814
Country 84479 0
Australia
Phone 84479 0
+61744331111
Fax 84479 0
Email 84479 0
andrew.maurice@uqconnect.edu.au
Contact person for scientific queries
Name 84480 0
Dr Andrew Maurice
Address 84480 0
Department of General Surgery
Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville, QLD, 4814
Country 84480 0
Australia
Phone 84480 0
+61744331111
Fax 84480 0
Email 84480 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 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.