Acute Focal AppendicitisAPRESNCT02795793
Non-operative Management for Appendicitis in Children
A study testing Non-operative management group (NOM) and Appendectomy group (Operative management, OM) in people with Acute Focal Appendicitis and Appendicitis, run by Sydney Children's Hospitals Network at 2 sites in Australia.
Trial summary
This study is designed to determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed acute uncomplicated appendicitis in children. Enrolled patients will be randomised and an allocation ratio of 1:1 will be made via weighted minimisation, where half of the patients will receive… Read more about this study
- Who is it for?
- Ages 5 to 16 years
- Conditions the study is for
- Acute Focal Appendicitis, Appendicitis
- What is being tested?
- Non-operative management group (NOM) and Appendectomy group (Operative management, OM)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 226 participants
- Where
- 2 sitesAustralia
- Study dates
- May 2016to Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age between 5 and 15 years;
- Clinical diagnosis by at least one paediatric surgeon (or duty surgical registrar) of acute uncomplicated appendicitis based on with a combination of clinical, laboratory and/or imaging findings; that before the study would have led to the decision to recommend been subjected to an appendicectomy.
- Exclusion Criteria: if one or more of the following is assessed to be present
- Suspicion of perforated appendicitis on the basis of generalised peritonitis and/or imaging studyA diagnosis of perforated or complicated appendicitis (e.g. peritonitis, appendiceal mass) is made on the basis of clinical, laboratory and/or imaging findings;
- Previous non-operative treatment of acute appendicitis;
- Age younger than 5 years or older than 16 years;
Show all 11Show fewer
- Known intolerance or allergy to Piperacillin with Tazobactam;
- Known history of inflammatory bowel disease, or other chronic abdominal pain syndrome;
- Known concurrent significant illness;
- Unable to obtain informed consent from parents or guardian;
- Known to have a cognitive impairment, an intellectual disability or a mental illness that would impair participation.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites, 2 recruiting
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
Susan Adams, MBBS
Susan Adams, MBBS
- Not yet recruiting
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Jonathon Karpewlosky, MBBCh
Jonathon Karpelowsky, MBBCh
About this study
Official title: A Prospective Randomised Controlled Non-inferiority Study to Evaluate the Effectiveness and Safety (APRES) of Non-operative Management in Children With Acute Uncomplicated Appendicitis
This study is designed to determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed acute uncomplicated appendicitis in children. Enrolled patients will be randomised and an allocation ratio of 1:1 will be made via weighted minimisation, where half of the patients will receive non-operative management with intravenous Piperacillin with Tazobactam, while the other half will have an appendicectomy.
Read the detailed description
Appendicectomy for acute appendicitis is one of the most commonly performed paediatric emergency operations in Australia. This standard treatment of acute uncomplicated appendicitis (AUA) has remained largely unchallenged since its introduction in the late nineteenth century, under the assumption that AUA progresses to perforation and thus complications should an operation be withheld. However, appendicectomy via laparoscopic or open approach is not without its risks.
Non-operative management (NOM) with antibiotics has been increasingly accepted as mainstay therapy for many intra-abdominal infections. In fact, children with appendicitis complicated by perforation, abscess or phlegmon formation are often preferentially treated non-operatively with antibiotic therapy, with or without percutaneous drainage. Systematic reviews and meta-analyses have demonstrated that antibiotics are a safe and effective treatment for AUA in adults and there is growing evidence that NOM is safe and effective in children.
Primary objectives:
To determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed likely AUA in children.
Secondary objectives:
- To compare the safety and efficacy of NOM of clinically diagnosed likely AUA with operative management (OM) in children.
- To assess the cost-effectiveness of NOM of clinically diagnosed likely AUA against OM in children.
- To assess the feasibility and acceptability of NOM of appendicitis in children.
This study will enrol 226 patients, age 5-16 years, with acute uncomplicated appendicitis at two tertiary children's hospitals. Allocation ratio of 1:1 will be made via weighted minimisation using the following criteria: age (5-8 years or 9-16 years), gender (male or female), and duration of symptoms (<48 or >48 hours).
- Conditions
- Acute Focal Appendicitis, Appendicitis
- Being tested
- Non-operative management group (NOM), Appendectomy group (Operative management, OM)
- Keywords
- appendicitis, non-operative management, children, pediatric
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-operative management group (NOM)Drug
With intravenous Piperacillin with Tazobactam (Tazocin)
Appendectomy group (Operative management, OM)Procedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Non-operative management group (NOM) | Experimental | Children in the NOM group will receive intravenous Piperacillin with Tazobactam (Tazocin) 100mg/kg/dose every 8 hours for at least 24 hours, and they will be observed and reassessed within 24 hours after randomisation. A further 24 hours of intravenous Piperacillin with Tazobactam therapy will be offered to children in invariable condition. A clinical decision will be made by the attending surgeon to offer OM if a patient's condition deteriorates at any time, or if a patient has failed to improve after 48 hours of intravenous antibiotic therapy. Once the patient is clinically improving and tolerating oral intake, the antibiotic regimen will be changed to oral Amoxicillin plus Clavulanic acid (Augmentin) 22.5mg/kg/dose twice per day to complete a total seven day course of antibiotics. Oral Ciprofloxacin 15mg/kg/dose twice daily and oral Metronidazole 10mg/kg/dose twice daily will be offered to children who are known to have an intolerance or allergy to Amoxicillin or Clavulanic acid. Receives: Drug: Non-operative management group (NOM) |
| Appendectomy group (Operative management, OM) | Active comparator | Children allocated to OM may receive preoperative antibiotic prophylaxis as clinically indicated. Appendicectomy will be performed laparoscopically, or via open surgery according to the surgeon's standard practice. Postoperative antibiotic treatment will be determined on the basis of intraoperative findings in accordance with the institutional practice. The appendix specimen will be examined by a paediatric pathologist, and the formal histopathology report will be recorded. Receives: Procedure: Appendectomy group (Operative management, OM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unplanned or unnecessary operation(s) and complications
Measured: 30 days
Secondary outcomes (7)
Unplanned or unnecessary operation, or complications
Measured: 6 months
Length of primary hospital stay
Time of randomisation to discharge
Measured: 72 hours
Treatment-related complications
Measured: 12 months
Redamission and Emergency Department presentation
Measured: 12 months
Cost of treatment in Australian Dollars (AUD)
Measured: 12 months
Return to school from time of randomisation
Measured: 30 days
Return to normal activities from time of randomisation
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionMay 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Focal AppendicitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 226 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sydney Children's Hospitals Network
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Susan Adams, Sydney Children's Hospitals Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02795793
- Sponsor's protocol ID
- HERC/15/SCHN/266
- Acronym
- APRES
- Status last verified
- Sep 2018
- First submitted
- 29 May 2016
- Last updated
- 18 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Xu J, Liu YC, Adams S, Karpelowsky J. Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis. BMJ Open. 2016 Dec 21;6(12):e013299. doi: 10.1136/bmjopen-2016-013299.
PubMed 28003294
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomised Controlled Non-inferiority Study to Evaluate the Effectiveness and Safety (APRES) of Non-operative Management in Children With Acute Uncomplicated Appendicitis
- ClinicalTrials.gov ID
- NCT02795793
- Acronym / sponsor ID
- APRES / HERC/15/SCHN/266
- Conditions
- Acute Focal Appendicitis, Appendicitis
- Keywords
- appendicitis, non-operative management, children, pediatric
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 226 participants (estimated)
- Lead sponsor
- Sydney Children's Hospitals NetworkUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- May 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed acute uncomplicated appendicitis in children. Enrolled patients will be randomised and an allocation ratio of 1:1 will be made via weighted minimisation, where half of the patients will receive non-operative management with intravenous Piperacillin with Tazobactam, while the other half will have an appendicectomy.
Detailed description
Appendicectomy for acute appendicitis is one of the most commonly performed paediatric emergency operations in Australia. This standard treatment of acute uncomplicated appendicitis (AUA) has remained largely unchallenged since its introduction in the late nineteenth century, under the assumption that AUA progresses to perforation and thus complications should an operation be withheld. However, appendicectomy via laparoscopic or open approach is not without its risks.
Non-operative management (NOM) with antibiotics has been increasingly accepted as mainstay therapy for many intra-abdominal infections. In fact, children with appendicitis complicated by perforation, abscess or phlegmon formation are often preferentially treated non-operatively with antibiotic therapy, with or without percutaneous drainage. Systematic reviews and meta-analyses have demonstrated that antibiotics are a safe and effective treatment for AUA in adults and there is growing evidence that NOM is safe and effective in children.
Primary objectives:
To determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed likely AUA in children.
Secondary objectives:
- To compare the safety and efficacy of NOM of clinically diagnosed likely AUA with operative management (OM) in children.
- To assess the cost-effectiveness of NOM of clinically diagnosed likely AUA against OM in children.
- To assess the feasibility and acceptability of NOM of appendicitis in children.
This study will enrol 226 patients, age 5-16 years, with acute uncomplicated appendicitis at two tertiary children's hospitals. Allocation ratio of 1:1 will be made via weighted minimisation using the following criteria: age (5-8 years or 9-16 years), gender (male or female), and duration of symptoms (<48 or >48 hours).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-operative management group (NOM) | Experimental | Drug: Non-operative management group (NOM)Children in the NOM group will receive intravenous Piperacillin with Tazobactam (Tazocin) 100mg/kg/dose every 8 hours for at least 24 hours, and they will be observed and reassessed within 24 hours after randomisation. A further 24 hours of intravenous Piperacillin with Tazobactam therapy will be offered to children in invariable condition. A clinical decision will be made by the attending surgeon to offer OM if a patient's condition deteriorates at any time, or if a patient has failed to improve after 48 hours of intravenous antibiotic therapy. Once the patient is clinically improving and tolerating oral intake, the antibiotic regimen will be changed to oral Amoxicillin plus Clavulanic acid (Augmentin) 22.5mg/kg/dose twice per day to complete a total seven day course of antibiotics. Oral Ciprofloxacin 15mg/kg/dose twice daily and oral Metronidazole 10mg/kg/dose twice daily will be offered to children who are known to have an intolerance or allergy to Amoxicillin or Clavulanic acid. |
| Appendectomy group (Operative management, OM) | Active comparator | Procedure: Appendectomy group (Operative management, OM)Children allocated to OM may receive preoperative antibiotic prophylaxis as clinically indicated. Appendicectomy will be performed laparoscopically, or via open surgery according to the surgeon's standard practice. Postoperative antibiotic treatment will be determined on the basis of intraoperative findings in accordance with the institutional practice. The appendix specimen will be examined by a paediatric pathologist, and the formal histopathology report will be recorded. |
Who may qualify
- Ages
- 5 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Age between 5 and 15 years;
- Clinical diagnosis by at least one paediatric surgeon (or duty surgical registrar) of acute uncomplicated appendicitis based on with a combination of clinical, laboratory and/or imaging findings; that before the study would have led to the decision to recommend been subjected to an appendicectomy.
- Exclusion Criteria: if one or more of the following is assessed to be present
- Suspicion of perforated appendicitis on the basis of generalised peritonitis and/or imaging studyA diagnosis of perforated or complicated appendicitis (e.g. peritonitis, appendiceal mass) is made on the basis of clinical, laboratory and/or imaging findings;
- Previous non-operative treatment of acute appendicitis;
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-operative management group (NOM)With intravenous Piperacillin with Tazobactam (Tazocin) | Drug | Non-operative management group (NOM) |
| Appendectomy group (Operative management, OM) | Procedure or surgery | Appendectomy group (Operative management, OM) |
Primary outcome
Unplanned or unnecessary operation(s) and complications
Time frame: 30 days
7 secondary outcomes
Unplanned or unnecessary operation, or complications
Time frame: 6 months
Length of primary hospital stay
Time frame: 72 hours
Treatment-related complications
Time frame: 12 months
Redamission and Emergency Department presentation
Time frame: 12 months
Cost of treatment in Australian Dollars (AUD)
Time frame: 12 months
Return to school from time of randomisation
Time frame: 30 days
Return to normal activities from time of randomisation
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Derived from this study: PubMed 28003294Xu J, Liu YC, Adams S, Karpelowsky J. Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis. BMJ Open. 2016 Dec 21;6(12):e013299. doi: 10.1136/bmjopen-2016-013299.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Non-operative management group (NOM) and Appendectomy group (Operative management, OM) in people with Acute Focal Appendicitis and Appendicitis, run by Sydney Children's Hospitals Network at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Susan Adams, MBBS (61 02 9382 1776, susan.adams@unsw.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unplanned or unnecessary operation(s) and complications (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02795793, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2018.