Clinical trial NCT02848820: Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Appendicitis
Keywords: Appendicitis
Appendectomy
Antibiotics
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Amsterdam UMC, location VUmc
First posted: 2016-07-29
Enrollment: 302
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients experiencing complications
timeFrame: One year follow up
Secondary outcomes:
measure: Number of days absent from school, social or sport events
timeFrame: 7 days, 1,6,12 months
measure: Number of days absent from work
timeFrame: 7 days, 1,6,12 months
measure: Total number of extra visits (not the already scheduled ones) to the outpatient clinic, general practitioners office or emergency department for abdominal pain.
timeFrame: 7 days, 1,6,12 months
measure: Total length of hospital stay during the follow-up period for strategy related treatment or complications
timeFrame: 7 days, 1,6,12 months
measure: Total days of analgesics medication use.
timeFrame: one month
measure: Pain score measured by the Visual Analogue Scale (VAS)
timeFrame: Clinical phase (up to 7 days)
measure: Proportion of patients with missed diagnosis of complex appendicitis with risk of peritonitis
timeFrame: 7 days, 1,6,12 months
measure: Proportion of patients not having to undergone appendectomy
timeFrame: 7 days, 1,6,12 months
measure: Proportion of patients experiencing recurrent appendicitis
timeFrame: 7 days, 1,6,12 months
measure: Proportion of patients experiencing early failure of initial non-operative treatment.
timeFrame: 7 days, 1,6,12 months
measure: Proportion of patients that undergo interval appendectomy.
timeFrame: 7 days, 1,6,12 months
measure: Quality of life questionnaire (CHQ-CF87, EQ-5d-Youth, EQ-5d-Proxy)
timeFrame: 7 days, 1,6,12 months
measure: Medical and non-medical costs (Health and Labor questionnaire)
timeFrame: 1,6,12 months
measure: Quality adjusted life years (QALY's). Calculating using outcome 13 and 14
timeFrame: 1,6,12 months
measure: Patient satisfaction questionnaire (PSQ-18 & Net promotor score)
timeFrame: 7 days, 1,6,12 months
measure: Promoting and obstructing factors of implementability measured by questionnaires
timeFrame: 12 months
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medical Center Alkmaar
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amstelveen
country: Netherlands
facility: Amstelland
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: VU University medical center
city: Apeldoorn
country: Netherlands
facility: Gelre Hospital
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Beverwijk
country: Netherlands
facility: Red Cross Hospital
city: Den Haag
country: Netherlands
facility: Haga ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer
city: Eindhoven
country: Netherlands
facility: Maxima medical center
city: Heerlen
country: Netherlands
facility: Zuyderland
city: Nieuwegein
country: Netherlands
facility: Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Franciscus, Gasthuis en Vlietland
Study officials:
affiliation: Pediatric Surgical Center of Amsterdam (VUmc & AMC)
name: Ernst van Heurn, MD PhD
role: STUDY_CHAIR
affiliation: Pediatric Surgical Center of Amsterdam (VUmc & AMC)
name: Ramon Gorter, MD
role: STUDY_DIRECTOR
affiliation: Pediatric Surgical Center of Amsterdam (VUmc & AMC)
name: Roel Bakx, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.