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Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population

Completed
Conditions
Appendix Mass
Appendicitis Perforated
Appendicitis
Interventions
Procedure: Non-operative treatment
Procedure: Laparoscopic appendectomy
Procedure: Direct appendectomy
Procedure: Open appendectomy
Registration Number
NCT04755179
Lead Sponsor
Ramon Gorter
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1308
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)

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Complex appendicitis with abscess or mass formationDirect appendectomyAll children (\<18 years old) that present with a suspicion of complex appendicitis with clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Complex appendicitis without abscess or mass formationOpen appendectomyAll children (\<18 years old) that present with a suspicion of complex appendicitis without clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Complex appendicitis with abscess or mass formationNon-operative treatmentAll children (\<18 years old) that present with a suspicion of complex appendicitis with clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Complex appendicitis without abscess or mass formationLaparoscopic appendectomyAll children (\<18 years old) that present with a suspicion of complex appendicitis without clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Primary Outcome Measures
NameTimeMethod
Overall complications3 months

The proportion of patients experiencing any complication within 3 months after inclusion

Secondary Outcome Measures
NameTimeMethod
Secondary bowel obstruction3 months

Proportion of patients with a secondary/prolonged bowel obstruction

Days absent from school, social or sports events30 days, 3 months

Number of days absent from school, social or sports events

Length of hospital stay3 months

Total length of hospital stay during follow-up due to trategy related treatment or complications

Pain medication utilization30 days, 3 months

Pain medication utilization during admission

Quality of Life questionnaire (PedsQL 4.0)at inclusion/baseline (=day 0), 30 days, 3 months

QoL measured by the validated Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (0-100 points, higher scores indicating better outcome) Labor Questionnaire (HLQ), Medical Consumption Questionnaire (iMCQ) and Productivity Consumption Questionnaire (iPCQ) and gathered actual health care cost

Superficial Site Infection3 months

Proportion of patients with a superficial site infection

Quality adjusted life months (QALM's)3 months

Quality adjusted life months calculated using outcomes 14 -17

Number of days absent from work30 days, 3 months

Number of days that parents are absent from work

Level of painat inclusion/baseline (=day 0), 3 days, 5 days, 30 days, 3 months

Level of pain measured according to the Visual Analogue Scale (0-10 points, higher scores indicating worse outcomes)

Need for appendectomy3 months

Proportion of patients not having to undergo appendectomy within 3 months after start of non-operative treatment

Recurrent appendicitis3 months

Proportion of patients experiencing recurrent appendicitis within 3 months after inclusion

Early failure of non-operative treatment3 months

Proportion of patients experiencing early failure of initial non-operative treatment

Medical costs (iMCQ)at inclusion/baseline (=day 0), 30 days, 3 months

Medical costs measured by the iMedical Consumption Questionnaire

Patient satisfaction questionnaire (PSQ-18)3 months

Patient satisfaction measured by the Patient Satisfaction Questionnaire (PSQ) (0-100, higher scores indicating better outcome)

Quality of Life questionnaire (EQ-5d-Youth/EQ-5d-Proxy)at inclusion/baseline (=day 0), 30 days, 3 months

QoL measured by the validated EQ-5d-Youth / EQ-5d-Proxy questionnaire (0-1 point, higher scores indicating better outcome)

Non-medical / indirect costs (iPCQ)at inclusion/baseline (=day 0), 30 days, 3 months

Non-medical / indirect costs measured by the iProductivity Cost Questionnaire

Postappendectomy abscess3 months

Proportion patients with a postappendectomy abscess

Total number of extra visits30 days, 3 months

Total number of extra visits to the outpatient clinic, general pratctitioner's office or emergency department

Patient satisfaction questionnaire (Net promotor score)3 months

Patient satisfaction measured by the NET PROMOTOR SCORE (0-10, higher scores indicating better outcome)

Trial Locations

Locations (32)

Gelre hospital

🇳🇱

Apeldoorn, Netherlands

Rijnstate

🇳🇱

Arnhem, Netherlands

Admiraal de Ruyter Hospital

🇳🇱

Goes, Netherlands

Zaans Medical Centre

🇳🇱

Zaandam, Netherlands

Northwest hospital group

🇳🇱

Alkmaar, Netherlands

Tergooi

🇳🇱

Blaricum, Netherlands

Haga/JKZ

🇳🇱

Den Haag, Netherlands

Isala

🇳🇱

Zwolle, Netherlands

Flevoziekenhuis

🇳🇱

Almere, Netherlands

Amsterdam UMC - Location AMC

🇳🇱

Amsterdam, Netherlands

OLVG

🇳🇱

Amsterdam, Netherlands

IJsselland Hospital

🇳🇱

Capelle Aan Den IJssel, Netherlands

Catharina hospital

🇳🇱

Eindhoven, Netherlands

Zuyderland MC

🇳🇱

Heerlen, Netherlands

Ikazia

🇳🇱

Rotterdam, Netherlands

Maasstad Hospital

🇳🇱

Rotterdam, Netherlands

Amsterdam UMC - Location VUmc

🇳🇱

Amsterdam, Netherlands

Albert Schweitzer Hospital

🇳🇱

Dordrecht, Netherlands

Hospital Amstelland

🇳🇱

Amstelveen, Netherlands

UMCG

🇳🇱

Groningen, Netherlands

Meander MC

🇳🇱

Amersfoort, Netherlands

Red Cross Hospital

🇳🇱

Beverwijk, Netherlands

Amphia

🇳🇱

Breda, Netherlands

Bravis Hospital

🇳🇱

Bergen Op Zoom, Netherlands

Sint Antonius Hospital

🇳🇱

Nieuwegein, Netherlands

Spaarne Gasthuis

🇳🇱

Haarlem, Netherlands

Dijklander

🇳🇱

Hoorn, Netherlands

Laurentius

🇳🇱

Roermond, Netherlands

Radboud UMC

🇳🇱

Nijmegen, Netherlands

Franciscus Gasthuis & Vlietland

🇳🇱

Rotterdam, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Maxima Medical Centre

🇳🇱

Veldhoven, Netherlands

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