Clinical trial NCT04755179: Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population
Official title: The Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Appendicitis
Appendix Mass
Appendicitis Perforated
Keywords: Complex appendicitis
Children
Treatment
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: 2021-02-16
Enrollment: 1308
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All children that present with a preoperative suspicion of complex appendicitis. This suspicion is based on 4 points or more on the abovementioned complex appendicitis scoring system OR a high index of suspicion of complex appendicitis by the treating physician.

Brief summary: Aim of this study is to evaluate the effect of different treatment strategies on overall complications, health related-Quality of Life (hr-QOL) and costs among two subtypes of complex appendicitis in children (\<18 years old).

Main research questions: What is the difference in overall complications at three months between:

Subgroup 1 (complex appendicitis without abscess/mass formation): Laparoscopic (LA) and open appendectomy (OA) Subgroup 2: (complex appendicitis with abscess/mass formation): Non-operative treatment (NOT) and direct appendectomy

Detailed description: Up till now initiated research projects worldwide mainly focus on simple appendicitis (questioning the necessity of an appendectomy). However, complex appendicitis is associated with significant morbidity (up to 30%), prolonged hospital stay and high costs. Identification of the optimal treatment strategy for children with complex appendicitis is therefore essential. Heterogeneity in the treatment of complex appendicitis still exists in daily practice and reflects the lack of high-quality data and emphasizes the need for well-designed studies. Complex appendicitis can be divided into two subtypes:

1. Complex appendicitis without mass/abscess. (subgroup 1) Although (inter)national guidelines agree that appendectomy should be usual care, the optimal approach (open or laparoscopy) is unclear. Laparoscopic appendectomy (LA) is increasingly applied both in adults (80%) and children (60%). Benefits reported for LA in children are, but not limited to, less superficial site infection (SSI), reduced length of hospital stay and significant less postoperative bowel obstruction compared with open appendectomy (OA). Reluctance for usage of LA in this specific subgroup, however, remains due to the potential higher incidence of post-appendectomy abscess formation (PAA) reported. However, the quality of studies on this topic is low and there is considerable inconsistency in results.
2. Complex appendicitis with mass/abscess. (subgroup 2) The recommendation made in our national guideline (to perform direct appendectomy in this subgroup) is not in line with the available literature. A recent Cochrane review on this topic could only include two trials and stated that no firm conclusions could be drawn. An older systematic review, including 7 studies in children, concluded that non-operative treatment (NOT) led to fewer complications, specifically SSI and PAA, when compared to direct appendectomy. Still the recommendation from our national guideline is to perform a direct appendectomy based upon good experiences in the pediatric academic centers.

In order to investigate the optimal treatment for children with complex appendicitis we will perform a nationwide, multi-center, comparative, prospective cohort study. For the purpose of this study, treatment strategies will be standardized among the participating hospitals in order to reduce heterogeneity. Prospectively derived, high quality data will be sufficient to answer the research questions regarding the optimal treatment strategy for each subtype of complex appendicitis in the pediatric population. As it is a non-randomized prospective cohort study, propensity score matching technique will be performed in order to estimate the effect of the treatments adjusted for potential confounders.

Eligibility criteria: Inclusion Criteria:

Eligible for inclusion are all children \<18 years old that need to undergo treatment for the suspicion of complex appendicitis. Suspicion of complex appendicitis is based upon the following predefined criteria:

4 or more points on our scoring system developed to predict complex appendicitis. The diagnostic accuracy of this scoring system is 91% (Range: 84-98%). This scoring system consists of five variables (clinical, biochemical and radiological,each awarded points). In case the total score is 4 or more points, the patient is likely to have complex appendicitis. Variables included in the scoring system are:

* Diffuse abdominal guarding (3 points)
* CRP level more than 38 mg/L (2 points)
* Signs on ultrasound / imaging indicative for complex appendicitis (2 points)
* More than one day abdominal pain (2 points)
* Temperature more than 37.5 degrees Celsius (1 point)

Or

High index of suspicion of complex appendicitis by the treating physician. If this is the case, the treating physician will make pre-treatment note upon what clinical, biochemical or radiological variable the high index of suspicion is based.

Exclusion Criteria:

* Adult patients (=18 years old)
* Children with a suspicion of simple appendicitis (based upon the previous mentioned scoring system and radiological features)

Primary outcomes:
measure: Overall complications
timeFrame: 3 months
Secondary outcomes:
measure: Postappendectomy abscess
timeFrame: 3 months
measure: Superficial Site Infection
timeFrame: 3 months
measure: Secondary bowel obstruction
timeFrame: 3 months
measure: Days absent from school, social or sports events
timeFrame: 30 days, 3 months
measure: Number of days absent from work
timeFrame: 30 days, 3 months
measure: Total number of extra visits
timeFrame: 30 days, 3 months
measure: Length of hospital stay
timeFrame: 3 months
measure: Level of pain
timeFrame: at inclusion/baseline (=day 0), 3 days, 5 days, 30 days, 3 months
measure: Pain medication utilization
timeFrame: 30 days, 3 months
measure: Need for appendectomy
timeFrame: 3 months
measure: Recurrent appendicitis
timeFrame: 3 months
measure: Early failure of non-operative treatment
timeFrame: 3 months
measure: Quality of Life questionnaire (EQ-5d-Youth/EQ-5d-Proxy)
timeFrame: at inclusion/baseline (=day 0), 30 days, 3 months
measure: Quality of Life questionnaire (PedsQL 4.0)
timeFrame: at inclusion/baseline (=day 0), 30 days, 3 months
measure: Medical costs (iMCQ)
timeFrame: at inclusion/baseline (=day 0), 30 days, 3 months
measure: Non-medical / indirect costs (iPCQ)
timeFrame: at inclusion/baseline (=day 0), 30 days, 3 months
measure: Quality adjusted life months (QALM's)
timeFrame: 3 months
measure: Patient satisfaction questionnaire (PSQ-18)
timeFrame: 3 months
measure: Patient satisfaction questionnaire (Net promotor score)
timeFrame: 3 months
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Northwest hospital group
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander MC
city: Amstelveen
country: Netherlands
facility: Hospital Amstelland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Location AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Location VUmc
city: Amsterdam
country: Netherlands
facility: OLVG
city: Apeldoorn
country: Netherlands
facility: Gelre hospital
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Bergen Op Zoom
country: Netherlands
facility: Bravis Hospital
city: Beverwijk
country: Netherlands
facility: Red Cross Hospital
city: Blaricum
country: Netherlands
facility: Tergooi
city: Breda
country: Netherlands
facility: Amphia
city: Capelle Aan Den IJssel
country: Netherlands
facility: IJsselland Hospital
city: Den Haag
country: Netherlands
facility: Haga/JKZ
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Eindhoven
country: Netherlands
facility: Catharina hospital
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Hospital
city: Groningen
country: Netherlands
facility: UMCG
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
city: Heerlen
country: Netherlands
facility: Zuyderland MC
city: Hoorn
country: Netherlands
facility: Dijklander
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Hospital
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Roermond
country: Netherlands
facility: Laurentius
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
city: Rotterdam
country: Netherlands
facility: Ikazia
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Veldhoven
country: Netherlands
facility: Maxima Medical Centre
city: Zaandam
country: Netherlands
facility: Zaans Medical Centre
city: Zwolle
country: Netherlands
facility: Isala
Study officials:
affiliation: Amsterdam UMC
name: Ramon Gorter, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Amstel P, Bakx R, van der Lee JH, van der Weide MC, Eekelen RV, Derikx JPM, van Heurn ELW, Gorter RR; CAPP collaborative study group. Identification of the optimal treatment strategy for complex appendicitis in the paediatric population: a protocol for a multicentre prospective cohort study (CAPP study). BMJ Open. 2022 Feb 17;12(2):e054826. doi: 10.1136/bmjopen-2021-054826.