Efficacy of non operative treatment with amoxicillin/clavulanic acid versus surgical treatment in acute uncomplicated appendicitis in children: a prospective multicenter randomized controlled non-inferiority trial with cost utility analysis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2025-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministry of Health - DGOS - France

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

is to evaluate the non-inferiority in terms of efficacy at one year of the Non Operative Treatment with amoxicillin/clavulanic acid (80mg/kg/day of amoxicillin) IV for a minimum of 24 hours and a maximum of 48 hours with a relay of Amoxicillin/clavulanic acid (80mg/kg/day) PO in 3 doses daily versus Surgical Treatment.

Secondary objectives 5

1. 1. To evaluate the efficiency of the intervention (cost-utility analyses) from the payer’s perspective (health insurance) and according to a time horizon of 12 months 2. To compare the 2 groups in terms of: a) initial success rate at Day 12 b) quality of life of children at inclusion, 30 days and 1 year c) quality of life of parents at inclusion, 30 days and 1 year 3. To analyze healthcare consumption during the one-year follow-up period 4. Using consumption data available in SNDS database, describe child care pathways over 5 years (i.e.Rehospitalization, appendectomy). 5. To describe safety at day 30 and at one year of the Non Operative Treatment and of the Surgical Treatment.
2. 2. To compare the 2 groups in terms of: a) initial success rate at Day 12 b) quality of life of children at inclusion, 30 days and 1 year c) quality of life of parents at inclusion, 30 days and 1 year
3. 3. To analyze healthcare consumption during the one-year follow-up period
4. 4. Using consumption data available in SNDS database, describe child care pathways over 5 years (i.e.Rehospitalization, appendectomy).
5. 5. To describe safety at day 30 and at one year of the Non Operative Treatment and of the Surgical Treatment.

Conditions and MedDRA coding

uncomplicated appendicitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age from 5 to <15 years-old
2. Diagnosis of first episode of acute uncomplicated appendicitis (abdominal pain, non-septic clinical aspect: good general condition, normal haemodynamic status, normal diuresis evaluated at clinical examination., and ultrasound and biology or CT scan (in cases where the appendix is not visible on ultrasound) confirming the diagnosis: - an increase in the calibre of the appendix, measured at more than 6 mm in diameter and non-compressibility - free fluid, echogenic fat, regional hyperemia - performed in hospital or reviewed by local radiologist investigators if performed outpatient.)
3. - Surgery expected within 24 hours after diagnosis
4. Parental good understanding of the monitoring French instructions
5. Free and informed consent, signed by both holders of parental authority/legal representative, with the accord of the minor patient
6. Affiliation to the health insurance plan

Exclusion criteria 16

1. Ultrasound or CT scan showing one or several stercoliths, a plastron, an abscess or peritonitis
2. Known immunodepression, ongoing immunosuppressive treatment, diabetes
3. Severe hematologic disorders (such as bone marrow failure, blood clotting disorders)
4. o History of proved allergy to Penicillin  History of proved allergy to amoxicillin and/or clavulanic acid  History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).  History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid History of allergy to any of the excipients listed in section 6.1 of each SmPC.
5. On going antibiotherapy : previous antibiotherapy have to be stopped at least 48h before inclusion
6. Parental refusal of research protocol
7. Impossibility of home follow-up after discharge from hospital
8. Renal insufficiency with creatinine clearance < 30 mL/min
9. Pregnancy/ breastfeeding
10. Presence of an appendicolith
11. situations contraindicating surgery or anesthesia (patient for whom surgery and anesthesia would pose a life-threatening risk)
12. patients who have already received antibiotic therapy for acute appendicitis/ongoing immunosuppressive treatment
13. Mental state rendering the person giving consent incapable of understanding the trial
14. Parents being a relative of the investigator or a relative of someone from the team directly involved in the trial, including assistant doctors, pharmacists, nurses, and trial coordinators
15. Simultaneously participation in another research study involving medicinal products
16. Non-visualization of the appendix at ultrasound or CT scan

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. percentage of treatment-related failures at one year defined as : - secondary surgery, - In surgery group, a normal appendix based on pathology or a complication requiring a new general anaesthesia - Readmissions for suspected appendicitis, emergency room visits related to appendicitis treatment, postoperative infections, adverse effects of antibiotics, adverse effects of anesthesia

Secondary endpoints 4

1. Differential cost-utility ratio between the two groups of treatment at one year
2. Direct Medical costs, and indirect costs (parental absenteeism) descriptions at 1 year
3. Using consumption data available in SNDS database, describe child care pathways over 5 years : Rehospitalization, appendectomy
4. Incidence of adverse events at day 30 and at one year in the two groups, and incidence of adverse events due to antibiotics in the NOT group

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

330 Avenue De Grande Bretagne

City

Toulouse Cedex 9

Postcode

31059

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Olivier ABBO

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Olivier ABBO

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications