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

Appendicitis Clinical Trial

— CAPP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04755179
• Other study ID #: W18_302#18.348
• Status: Recruiting
• Start date: August 12, 2019
• Est. completion date: July 12, 2023

Study information

• Verified date: July 2022
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Ramon Gorter, MD PhD
• Phone: 0031-205665693
• Email: rr.gorter[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 1308
• Est. completion date: July 12, 2023
• Est. primary completion date: May 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Appendicitis
• Appendicitis Perforated
• Appendix Mass

Intervention

Procedure:
• Laparoscopic appendectomy
Laparoscopic appendectomy is performed according to daily practice but with the following standardized key points: Conventional laparoscopy (three-trocar technique) In case of purulent fluid: Suction and no peritoneal lavage procedure Skelletizing of the mesoappendix (coagulation/clips according to routine practice locally) Appendiceal stump closure: with two endoloops and dissected between the endoloops. In case of involvement of the appendiceal base, the use of endostapler is recommended. Withdrawal of appendix: principle of abdominal wall protection is followed (trocar technique / endobag) No drain placement, no nasogastric tube, and no urinary catheter routinely, only on indication. Closure of wounds as appropriate
• Open appendectomy
Open appendectomy will be performed according to the following standardized key points: Gridiron incision at the right lower quadrant. (McBurney's point) After obtaining access to the abdominal cavity the principle of abdominal wall protection will be followed. The appendiceal stump will be closed by ligation, not a purse string suture. Closure of wounds as appropriate
• Non-operative treatment
Non-operative treatment consisting of administration of intravenous antibiotics with or without drainage procedures (in case of an abscess), reserving an appendectomy for those not responding or with recurrent disease. One of the two antibiotic regiments: Combination A: Amoxicillin/clavulanic acid 25/2.5mg/kg 6 hourly (total 100/10 mg/kg daily. Maximum 6000/600mg a day) for children <40 kg OR Amoxicillin/clavulanic acid 1000/200mg/kg 8 hourly (total 3000/6000 mg/kg daily) for children > 40 kg Gentamicin 7mg/kg once daily Combination B: Cefuroxim 25 mg/kg 6 hourly (total 100 mg/kg/day. Maximum 6gram/day) Metronidazole 10mg/kg 8hourly (total 30 mg/kg/day. Maximum 4000 mg/day) In case of peri-appendicular abscess the decision can be made to perform a drainage procedure either percutaneously or surgical.
• Direct appendectomy
laparoscopic or open appendectomy as described

Locations

Country	Name	City	State
Netherlands	Northwest hospital group	Alkmaar
Netherlands	Flevoziekenhuis	Almere
Netherlands	Meander MC	Amersfoort
Netherlands	Hospital Amstelland	Amstelveen
Netherlands	Amsterdam UMC - Location AMC	Amsterdam
Netherlands	Amsterdam UMC - Location VUmc	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	Gelre hospital	Apeldoorn
Netherlands	Rijnstate	Arnhem
Netherlands	Bravis Hospital	Bergen Op Zoom
Netherlands	Red Cross Hospital	Beverwijk
Netherlands	Tergooi	Blaricum
Netherlands	Amphia	Breda
Netherlands	IJsselland Hospital	Capelle Aan Den IJssel
Netherlands	Haga/JKZ	Den Haag
Netherlands	Albert Schweitzer Hospital	Dordrecht
Netherlands	Catharina hospital	Eindhoven
Netherlands	Admiraal de Ruyter Hospital	Goes
Netherlands	UMCG	Groningen
Netherlands	Spaarne Gasthuis	Haarlem
Netherlands	Zuyderland MC	Heerlen
Netherlands	Dijklander	Hoorn
Netherlands	Sint Antonius Hospital	Nieuwegein
Netherlands	Radboud UMC	Nijmegen
Netherlands	Laurentius	Roermond
Netherlands	Erasmus MC	Rotterdam
Netherlands	Franciscus Gasthuis & Vlietland	Rotterdam
Netherlands	Ikazia	Rotterdam
Netherlands	Maasstad Hospital	Rotterdam
Netherlands	Maxima Medical Centre	Veldhoven
Netherlands	Zaans Medical Centre	Zaandam
Netherlands	Isala	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Ramon Gorter	Amsterdam UMC, location VUmc, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall complications	The proportion of patients experiencing any complication within 3 months after inclusion	3 months
Secondary	Postappendectomy abscess	Proportion patients with a postappendectomy abscess	3 months
Secondary	Superficial Site Infection	Proportion of patients with a superficial site infection	3 months
Secondary	Secondary bowel obstruction	Proportion of patients with a secondary/prolonged bowel obstruction	3 months
Secondary	Days absent from school, social or sports events	Number of days absent from school, social or sports events	30 days, 3 months
Secondary	Number of days absent from work	Number of days that parents are absent from work	30 days, 3 months
Secondary	Total number of extra visits	Total number of extra visits to the outpatient clinic, general pratctitioner's office or emergency department	30 days, 3 months
Secondary	Length of hospital stay	Total length of hospital stay during follow-up due to trategy related treatment or complications	3 months
Secondary	Level of pain	Level of pain measured according to the Visual Analogue Scale (0-10 points, higher scores indicating worse outcomes)	at inclusion/baseline (=day 0), 3 days, 5 days, 30 days, 3 months
Secondary	Pain medication utilization	Pain medication utilization during admission	30 days, 3 months
Secondary	Need for appendectomy	Proportion of patients not having to undergo appendectomy within 3 months after start of non-operative treatment	3 months
Secondary	Recurrent appendicitis	Proportion of patients experiencing recurrent appendicitis within 3 months after inclusion	3 months
Secondary	Early failure of non-operative treatment	Proportion of patients experiencing early failure of initial non-operative treatment	3 months
Secondary	Quality of Life questionnaire (EQ-5d-Youth/EQ-5d-Proxy)	QoL measured by the validated EQ-5d-Youth / EQ-5d-Proxy questionnaire (0-1 point, higher scores indicating better outcome)	at inclusion/baseline (=day 0), 30 days, 3 months
Secondary	Quality of Life questionnaire (PedsQL 4.0)	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	at inclusion/baseline (=day 0), 30 days, 3 months
Secondary	Medical costs (iMCQ)	Medical costs measured by the iMedical Consumption Questionnaire	at inclusion/baseline (=day 0), 30 days, 3 months
Secondary	Non-medical / indirect costs (iPCQ)	Non-medical / indirect costs measured by the iProductivity Cost Questionnaire	at inclusion/baseline (=day 0), 30 days, 3 months
Secondary	Quality adjusted life months (QALM's)	Quality adjusted life months calculated using outcomes 14 -17	3 months
Secondary	Patient satisfaction questionnaire (PSQ-18)	Patient satisfaction measured by the Patient Satisfaction Questionnaire (PSQ) (0-100, higher scores indicating better outcome)	3 months
Secondary	Patient satisfaction questionnaire (Net promotor score)	Patient satisfaction measured by the NET PROMOTOR SCORE (0-10, higher scores indicating better outcome)	3 months