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

NCT ID: NCT04755179

Last Updated: 2024-07-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1308 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-08-12
• Study Completion Date: 2024-07-03

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.

Conditions

Appendicitis; Appendix Mass; Appendicitis Perforated

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Complex appendicitis without abscess or mass formation

All 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.

Laparoscopic appendectomy

Intervention Type: PROCEDURE

Laparoscopic appendectomy is performed according to daily practice but with the following standardized key points:

1. Conventional laparoscopy (three-trocar technique)

2. In case of purulent fluid: Suction and no peritoneal lavage procedure

3. Skelletizing of the mesoappendix (coagulation/clips according to routine practice locally)

4. 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.

5. Withdrawal of appendix: principle of abdominal wall protection is followed (trocar technique / endobag)

6. No drain placement, no nasogastric tube, and no urinary catheter routinely, only on indication.

7. Closure of wounds as appropriate

Open appendectomy

Intervention Type: PROCEDURE

Open appendectomy will be performed according to the following standardized key points:

1. Gridiron incision at the right lower quadrant. (McBurney's point)

2. After obtaining access to the abdominal cavity the principle of abdominal wall protection will be followed.

3. The appendiceal stump will be closed by ligation, not a purse string suture.

4. Closure of wounds as appropriate

Complex appendicitis with abscess or mass formation

All 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.

Non-operative treatment

Intervention Type: PROCEDURE

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:

1. Combination A:

1. 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

2. Gentamicin 7mg/kg once daily

2. Combination B:

1. Cefuroxim 25 mg/kg 6 hourly (total 100 mg/kg/day. Maximum 6gram/day)

2. 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

Intervention Type: PROCEDURE

laparoscopic or open appendectomy as described

Interventions

Laparoscopic appendectomy

Laparoscopic appendectomy is performed according to daily practice but with the following standardized key points:

1. Conventional laparoscopy (three-trocar technique)

2. In case of purulent fluid: Suction and no peritoneal lavage procedure

3. Skelletizing of the mesoappendix (coagulation/clips according to routine practice locally)

4. 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.

5. Withdrawal of appendix: principle of abdominal wall protection is followed (trocar technique / endobag)

6. No drain placement, no nasogastric tube, and no urinary catheter routinely, only on indication.

7. Closure of wounds as appropriate

Intervention Type: PROCEDURE

Open appendectomy

Open appendectomy will be performed according to the following standardized key points:

1. Gridiron incision at the right lower quadrant. (McBurney's point)

2. After obtaining access to the abdominal cavity the principle of abdominal wall protection will be followed.

3. The appendiceal stump will be closed by ligation, not a purse string suture.

4. Closure of wounds as appropriate

Intervention Type: PROCEDURE

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:

1. Combination A:

1. 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

2. Gentamicin 7mg/kg once daily

2. Combination B:

1. Cefuroxim 25 mg/kg 6 hourly (total 100 mg/kg/day. Maximum 6gram/day)

2. 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.

Intervention Type: PROCEDURE

Direct appendectomy

laparoscopic or open appendectomy as described

Intervention Type: PROCEDURE

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)

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: collaborator

Ramon Gorter

OTHER

Sponsor Role: lead

Responsible Party

Ramon Gorter

Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ramon Gorter, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Northwest hospital group

Alkmaar, , Netherlands

Flevoziekenhuis

Almere Stad, , 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

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

Haga/JKZ

The Hague, , Netherlands

Maxima Medical Centre

Veldhoven, , Netherlands

Zaans Medical Centre

Zaandam, , Netherlands

Isala

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 35177453 (View on PubMed)

Other Identifiers

W18_302#18.348

Identifier Type: -

Identifier Source: org_study_id