Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children

NCT ID: NCT02848820

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2024-12-31

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.

Conditions

Appendicitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Augmentin + Gentamicin

Initial non-operative treatment strategy reserving an appendectomy for those not responding or with recurrent disease. It consist of:

Clinical observation for 48 hours with administration of Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) and gentamicin 7mg/kg once daily for 48 hours. If after 48 hours the patient fulfils the predefined discharge criteria, the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days and discharge. An appendectomy is reserved for those patients with clinical deterioration, non-improvement after 72 hours or recurrent appendicitis.

Pain medication according to national protocol.

Group Type: EXPERIMENTAL

Augmentin + Gentamicin

Intervention Type: DRUG

Amoxicillin/clavulanic acid (Augmentin) 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) intravenously for 48 hours Oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days Gentamicin 7mg/kg once daily for 48 hours

Operative treatment strategy

Clinical observation and semi-urgent appendectomy. Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics. Discharge if the patient fulfils the predefined discharge criteria. Pain medication according to national protocol.

Group Type: ACTIVE_COMPARATOR

Appendectomy

Intervention Type: PROCEDURE

Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics

Interventions

Augmentin + Gentamicin

Amoxicillin/clavulanic acid (Augmentin) 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) intravenously for 48 hours Oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days Gentamicin 7mg/kg once daily for 48 hours

Intervention Type: DRUG

Appendectomy

Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics

Intervention Type: PROCEDURE

Other Intervention Names

Amoxicillin/clavulanic acid (Augmentin) + Gentamicin

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.

• Minimum Eligible Age: 7 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

drs.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ernst van Heurn, MD PhD

Role: STUDY_CHAIR

Pediatric Surgical Center of Amsterdam (VUmc & AMC)

Ramon Gorter, MD

Role: STUDY_DIRECTOR

Pediatric Surgical Center of Amsterdam (VUmc & AMC)

Roel Bakx, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Surgical Center of Amsterdam (VUmc & AMC)

Locations

Medical Center Alkmaar

Alkmaar, , Netherlands

Flevoziekenhuis

Almere Stad, , Netherlands

Amstelland

Amstelveen, , Netherlands

AMC

Amsterdam, , Netherlands

OLVG

Amsterdam, , Netherlands

VU University medical center

Amsterdam, , Netherlands

Gelre Hospital

Apeldoorn, , Netherlands

Rijnstate

Arnhem, , Netherlands

Red Cross Hospital

Beverwijk, , Netherlands

Albert Schweitzer

Dordrecht, , Netherlands

Maxima medical center

Eindhoven, , Netherlands

Zuyderland

Heerlen, , Netherlands

Antonius Hospital

Nieuwegein, , Netherlands

Franciscus, Gasthuis en Vlietland

Rotterdam, , Netherlands

Haga ziekenhuis

The Hague, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 29146647 (View on PubMed)

Other Identifiers

APAC2016

Identifier Type: -

Identifier Source: org_study_id