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Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children (APAC)

Primary Purpose

Appendicitis

Status
Active
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Augmentin + Gentamicin
Appendectomy
Sponsored by
Ramon Gorter
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Appendicitis focused on measuring Appendicitis, Appendectomy, Antibiotics

Eligibility Criteria

7 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 7-17 years

  • Radiologically confirmed simple appendicitis, defined as:

    1. Clinical findings:

      • Unwell, but not generally ill
      • Localized tenderness in the right iliac fossa region
      • Normal/hyperactive bowel sounds
      • No guarding
      • No mass palpable

    2. Ultrasonography:

      • Incompressible appendix with an outer diameter of ≥6 mm
      • Hyperaemia within the appendiceal wall
      • Without faecolith
      • Infiltration of surrounding fat
      • No signs of perforation
      • No signs of intra-abdominal abscess/phlegmon

Exclusion Criteria:

  • Generalized peritonitis, complex appendicitis or sepsis (based upon predefined criteria and scoring system).

  • Scoring system: As scoring system was developed determining the risk of complex appendicitis based upon five pre-operative variable. Points have been awarded to each variable. In case the total score is less than 4 points, the patient is likely to have a simple appendicitis. In case the score is 4 or more points, the chance of having complex appendicitis is significant and those children will be excluded from this study. Variables:

    • Diffuse abdominal guarding (3 points)
    • C-Reactive Protein level more than 38 mg/L (2 points)
    • Signs on ultrasound indicative of complex appendicitis (2 points)
    • More than one day abdominal pain (2 points)
    • Temperature: more than 37.5 degree Celsius (1 point)
  • Faecolith (ultrasound)
  • Serious co-morbidity
  • Recurrent appendicitis
  • Suspicion of an underlying malignancy or inflammatory bowel disease
  • Documented type 1 allergy to the antibiotics used.

Sites / Locations

  • Medical Center Alkmaar
  • Flevoziekenhuis
  • Amstelland
  • AMC
  • OLVG
  • VU University medical center
  • Gelre Hospital
  • Rijnstate
  • Red Cross Hospital
  • Haga ziekenhuis
  • Albert Schweitzer
  • Maxima medical center
  • Zuyderland
  • Antonius Hospital
  • Franciscus, Gasthuis en Vlietland

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Augmentin + Gentamicin

Operative treatment strategy

Arm Description

Initial non-operative treatment strategy reserving an appendectomy for those not responding or with recurrent disease. It consist of: Clinical observation for 48 hours with administration of Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) and gentamicin 7mg/kg once daily for 48 hours. If after 48 hours the patient fulfils the predefined discharge criteria, the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days and discharge. An appendectomy is reserved for those patients with clinical deterioration, non-improvement after 72 hours or recurrent appendicitis. Pain medication according to national protocol.

Clinical observation and semi-urgent appendectomy. Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics. Discharge if the patient fulfils the predefined discharge criteria. Pain medication according to national protocol.

Outcomes

Primary Outcome Measures

Proportion of patients experiencing complications

Secondary Outcome Measures

Number of days absent from school, social or sport events
Number of days absent from work
Total number of extra visits (not the already scheduled ones) to the outpatient clinic, general practitioners office or emergency department for abdominal pain.
Total length of hospital stay during the follow-up period for strategy related treatment or complications
Total days of analgesics medication use.
Pain score measured by the Visual Analogue Scale (VAS)
Proportion of patients with missed diagnosis of complex appendicitis with risk of peritonitis
Proportion of patients not having to undergone appendectomy
Proportion of patients experiencing recurrent appendicitis
Proportion of patients experiencing early failure of initial non-operative treatment.
Proportion of patients that undergo interval appendectomy.
Quality of life questionnaire (CHQ-CF87, EQ-5d-Youth, EQ-5d-Proxy)
Medical and non-medical costs (Health and Labor questionnaire)
Quality adjusted life years (QALY's). Calculating using outcome 13 and 14
Patient satisfaction questionnaire (PSQ-18 & Net promotor score)
Promoting and obstructing factors of implementability measured by questionnaires

Full Information

First Posted
July 24, 2016
Last Updated
October 20, 2023
Sponsor
Ramon Gorter
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Amsterdam UMC, location VUmc
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1. Study Identification

Unique Protocol Identification Number
NCT02848820
Brief Title
Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children
Acronym
APAC
Official Title
Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children Aged 7-17 Years Old - Antibiotics Versus Primary Appendectomy in Children With Simple Appendicitis: APAC Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2016 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ramon Gorter
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Amsterdam UMC, location VUmc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
OBJECTIVE The aim of this study is to compare the effectiveness of initial non-operative treatment strategy (reserving appendectomy for those not responding or with recurrent disease) with immediate appendectomy in children from 7 to 17 years old, inclusive, with acute simple appendicitis in terms of complications, health-related QOL and costs. Main research question: What is the difference in proportion of patients experiencing complications within 1 year between both strategies in children from 7 to 17 years old, inclusive, with acute simple appendicitis?
Detailed Description
Initial non-operative treatment of acute simple appendicitis has recently been investigated in both the adult as the paediatric population. In the adult population, six Randomised Controlled Trial (RCTs) showed that an appendectomy could be avoided in 40-76% of the patients at the end of their follow-up period. Despite the fact that some patients need to undergo a delayed appendectomy, it has been demonstrated in systematic reviews that non-operative treatment strategy is associated with a significant reduction in complications, faster recovery and return to work, less pain duration and analgesic medication consumption. In children only pilot data is yet available. Short-term success rates of this strategy (including of the investigators own pilot cohort study) are between the 83-92%. Long-term results (one-year follow-up) are available from two studies; 62-75% did not require an appendectomy. No large RCT have yet been conducted in the paediatric population. It is therefore essential to generate high quality empirical evidence regarding this strategy in this subset of patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Appendicitis
Keywords
Appendicitis, Appendectomy, Antibiotics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Augmentin + Gentamicin
Arm Type
Experimental
Arm Description
Initial non-operative treatment strategy reserving an appendectomy for those not responding or with recurrent disease. It consist of: Clinical observation for 48 hours with administration of Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) and gentamicin 7mg/kg once daily for 48 hours. If after 48 hours the patient fulfils the predefined discharge criteria, the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days and discharge. An appendectomy is reserved for those patients with clinical deterioration, non-improvement after 72 hours or recurrent appendicitis. Pain medication according to national protocol.
Arm Title
Operative treatment strategy
Arm Type
Active Comparator
Arm Description
Clinical observation and semi-urgent appendectomy. Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics. Discharge if the patient fulfils the predefined discharge criteria. Pain medication according to national protocol.
Intervention Type
Drug
Intervention Name(s)
Augmentin + Gentamicin
Other Intervention Name(s)
Amoxicillin/clavulanic acid (Augmentin) + Gentamicin
Intervention Description
Amoxicillin/clavulanic acid (Augmentin) 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) intravenously for 48 hours Oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days Gentamicin 7mg/kg once daily for 48 hours
Intervention Type
Procedure
Intervention Name(s)
Appendectomy
Intervention Description
Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics
Primary Outcome Measure Information:
Title
Proportion of patients experiencing complications
Time Frame
One year follow up
Secondary Outcome Measure Information:
Title
Number of days absent from school, social or sport events
Time Frame
7 days, 1,6,12 months
Title
Number of days absent from work
Time Frame
7 days, 1,6,12 months
Title
Total number of extra visits (not the already scheduled ones) to the outpatient clinic, general practitioners office or emergency department for abdominal pain.
Time Frame
7 days, 1,6,12 months
Title
Total length of hospital stay during the follow-up period for strategy related treatment or complications
Time Frame
7 days, 1,6,12 months
Title
Total days of analgesics medication use.
Time Frame
one month
Title
Pain score measured by the Visual Analogue Scale (VAS)
Time Frame
Clinical phase (up to 7 days)
Title
Proportion of patients with missed diagnosis of complex appendicitis with risk of peritonitis
Time Frame
7 days, 1,6,12 months
Title
Proportion of patients not having to undergone appendectomy
Time Frame
7 days, 1,6,12 months
Title
Proportion of patients experiencing recurrent appendicitis
Time Frame
7 days, 1,6,12 months
Title
Proportion of patients experiencing early failure of initial non-operative treatment.
Time Frame
7 days, 1,6,12 months
Title
Proportion of patients that undergo interval appendectomy.
Time Frame
7 days, 1,6,12 months
Title
Quality of life questionnaire (CHQ-CF87, EQ-5d-Youth, EQ-5d-Proxy)
Time Frame
7 days, 1,6,12 months
Title
Medical and non-medical costs (Health and Labor questionnaire)
Time Frame
1,6,12 months
Title
Quality adjusted life years (QALY's). Calculating using outcome 13 and 14
Time Frame
1,6,12 months
Title
Patient satisfaction questionnaire (PSQ-18 & Net promotor score)
Time Frame
7 days, 1,6,12 months
Title
Promoting and obstructing factors of implementability measured by questionnaires
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 7-17 years Radiologically confirmed simple appendicitis, defined as: Clinical findings: Unwell, but not generally ill Localized tenderness in the right iliac fossa region Normal/hyperactive bowel sounds No guarding No mass palpable Ultrasonography: Incompressible appendix with an outer diameter of ≥6 mm Hyperaemia within the appendiceal wall Without faecolith Infiltration of surrounding fat No signs of perforation No signs of intra-abdominal abscess/phlegmon Exclusion Criteria: Generalized peritonitis, complex appendicitis or sepsis (based upon predefined criteria and scoring system). Scoring system: As scoring system was developed determining the risk of complex appendicitis based upon five pre-operative variable. Points have been awarded to each variable. In case the total score is less than 4 points, the patient is likely to have a simple appendicitis. In case the score is 4 or more points, the chance of having complex appendicitis is significant and those children will be excluded from this study. Variables: Diffuse abdominal guarding (3 points) C-Reactive Protein level more than 38 mg/L (2 points) Signs on ultrasound indicative of complex appendicitis (2 points) More than one day abdominal pain (2 points) Temperature: more than 37.5 degree Celsius (1 point) Faecolith (ultrasound) Serious co-morbidity Recurrent appendicitis Suspicion of an underlying malignancy or inflammatory bowel disease Documented type 1 allergy to the antibiotics used.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ernst van Heurn, MD PhD
Organizational Affiliation
Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ramon Gorter, MD
Organizational Affiliation
Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Roel Bakx, MD PhD
Organizational Affiliation
Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Center Alkmaar
City
Alkmaar
Country
Netherlands
Facility Name
Flevoziekenhuis
City
Almere
Country
Netherlands
Facility Name
Amstelland
City
Amstelveen
Country
Netherlands
Facility Name
AMC
City
Amsterdam
Country
Netherlands
Facility Name
OLVG
City
Amsterdam
Country
Netherlands
Facility Name
VU University medical center
City
Amsterdam
Country
Netherlands
Facility Name
Gelre Hospital
City
Apeldoorn
Country
Netherlands
Facility Name
Rijnstate
City
Arnhem
Country
Netherlands
Facility Name
Red Cross Hospital
City
Beverwijk
Country
Netherlands
Facility Name
Haga ziekenhuis
City
Den Haag
Country
Netherlands
Facility Name
Albert Schweitzer
City
Dordrecht
Country
Netherlands
Facility Name
Maxima medical center
City
Eindhoven
Country
Netherlands
Facility Name
Zuyderland
City
Heerlen
Country
Netherlands
Facility Name
Antonius Hospital
City
Nieuwegein
Country
Netherlands
Facility Name
Franciscus, Gasthuis en Vlietland
City
Rotterdam
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Will follow
Citations:
PubMed Identifier
29146647
Citation
Knaapen M, van der Lee JH, Bakx R, The SL, van Heurn EWE, Heij HA, Gorter RR; APAC collaborative study group. Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial). BMJ Open. 2017 Nov 15;7(11):e018145. doi: 10.1136/bmjopen-2017-018145.
Results Reference
derived

Learn more about this trial

Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children

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