Acute Uncomplicated AppendicitisPhase 3NACACNCT07587450
Efficacy of Non Operative Treatment With Amoxicillin/Clavulanic Acid Versus Surgical Treatment in Acute Uncomplicated Appendicitis in Children
A Phase 3 study testing Amoxi Clavulanate and appendicectomy in people with Acute Uncomplicated Appendicitis, run by University Hospital, Toulouse at 10 sites in France.
Trial summary
The majority of children with uncomplicated acute appendicitis may be considered for either a non-operative or an operative management. The antibiotic-first strategy appears effective as an initial treatment in 97% of children with uncomplicated AA (recurrence rate 14%), with Non Operative Treatment (NOT) also leading… Read more about this study
- Who is it for?
- Ages 5 to 14 years
- Conditions the study is for
- Acute Uncomplicated Appendicitis
- What is being tested?
- Amoxi Clavulanate and appendicectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 724 participants
- Where
- 10 sitesFrance
- Study dates
- 1 Sep 2026to 1 Sep 2034
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age from 5 to <15 years-old
- Diagnosis of first episode of acute uncomplicated appendicitis 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.
- Surgery expected within 24 hours after diagnosis
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- Parental good understanding of the monitoring French instructions
- Free and informed consent, signed by both holders of parental authority/legal representative, with the accord of the minor patient.
- Affiliation to the health insurance plan
Who cannot join
- Ultrasound or CT scan showing one or several stercoliths, a plastron, an abscess or peritonitis
- Non-visualization of the appendix at ultrasound or CT scan
- Situations contraindicating surgery or anesthesia (patient for whom surgery and anesthesia would pose a life-threatening risk)
- Patients who have already received antibiotic therapy for acute appendicitis
- Known immunodepression, ongoing immunosuppressive treatment, diabetes
- Severe hematologic disorders (such as bone marrow failure, blood clotting disorders)
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- 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.
- On going antibiotherapy : previous antibiotherapy have to be stopped at least 48h before inclusion
- Parental refusal of research protocol
- Impossibility of home follow-up after discharge from hospital
- Pregnancy/ breastfeeding
- Simultaneously participation in another research study involving medicinal products
- Mental state rendering the person giving consent incapable of understanding the trial
- 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
- Renal insufficiency with creatinine clearance < 30mL/min
- Presence of an appendicolith
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
France10 sites
CHU de Bordeaux - Pellerin
Bordeaux
Luke HARPER, luke.harper@chu-bordeaux.fr
Luke HARPER
Centre Hopsitalier Universitaire de Grenoble - Hôpital Nord
Grenoble
Romain FAGUET, Rfaguet@chu-grenoble.fr
Romain FAGUET
Centre Hospitalier Universitaire de Lille - Hôpital Salengro
Lille
Francois DUBOS, francois.dubos@chu-lille.fr
Francois DUBOS
Centre Hospitalier Universitaire de Limoges
Limoges
Quentin BALLOUHEY, Quentin.Ballouhey@chu-limoges.fr
Quentin BALLOUHEY
AP-HM Hopital Nord
Marseille
Anne DARIEL, anne.dariel@ap-hm.fr
Anne DARIEL
Centre Hospitalier Universitaire - Hôpital Lapeyronie
Montpellier
Nicolas KALFA, n-kalfa@chu-montpellier.fr
Nicolas KALFA
Centre Hospitalier Universitaire de Nantes - Hôtel-Dieu
Nantes
Marc-David LECLAIR, mdleclair@chu-nantes.fr
Marc-David LECLAIR
AP-HP Hôpital Trousseau
Paris
Sabine IRTAN, sabine.irtan@aphp.fr
Sabine IRTAN
Centre Hospitalier Régional Universitaire de Rennes
Rennes
Alexis ARNAUD, alexis.arnaud@chu-rennes.fr
Alexis ARNAUD
Centre Hospitalier Universitaire
Toulouse
Isabelle KIEFFER, kieffer.i@chu-toulouse.fr
Gwenaelle ALPHONSA, alphonsa.g@chu-toulouse.fr
About this study
Official title: 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
The majority of children with uncomplicated acute appendicitis may be considered for either a non-operative or an operative management. The antibiotic-first strategy appears effective as an initial treatment in 97% of children with uncomplicated AA (recurrence rate 14%), with Non Operative Treatment (NOT) also leading to less morbidity, fewer disability days, and lower costs than surgery. In this trial, the investigators will compare children randomised in a surgery group with children randomised in a NOT group (antibiotic strategy group). Children have 2 on-site visits (including surgery) in the first 12 days with recording of clinical datas and questionnaires, a phone visit at month 1, month 6, month 12 to collect concomitant treatment, Adverse Event (AE) and complications and parental questionnaires at the end of the study. A Cost-Utility analysis will be performed from the healthcare payer's perspective. The time horizon of the medico economic analysis was one year.
Read the detailed description
The design of the NACAC study is an open-label, randomized, multicenter controlled non-inferiority trial with 2 parallel groups: one group of patients will have appendectomy (ST), and the other group will receive antibiotic treatment (NOT).
Children in the non-operative treatment group will be hospitalised for clinical monitoring with initiation of antibiotic therapy at day 1 with Amoxicillin/clavulanic acid IntraVeinous (IV) in 2 doses daily for a minimum of 24 hours and a maximum of 48 hours with a relay of Amoxicillin/clavulanic acid Per Os (PO) in 2 doses daily, for a total of 7 days (IV and PO).
Children can be discharged from hospital after day 1 if the clinical conditions are safe.
In case of hypersensitivity to antibiotic administered the patient will be withdrawn from the study.
Children randomised to the Surgical Treatment group will be hospitalised for a surgical usual management within 24 hours, according to the surgical unit organisation.
For all patients a physical examination (same as inclusion) will be made by an investigator at Day 1 and discharge. Questionnaires will be assessed at D1 and discharge. At discharge, parental absenteism will be evaluated. For ST group, possible post-operative complication will also be evaluated. A visit on the investigator site from Day 10 to Day 15 : all the patients will have a complete physical examination (same as inclusion), child activity evolution and parental absenteeism will be evaluated.
An abdominal ultrasound or CT scan will be performed in patients randomized in the non-operative treatment group. AE and concomitant treatment will be assessed at this study visit by questioning, during the physical examination of the patient.
Compliance to study treatment will be reviewed at day 12 in the NOT group. For ST group, possible post-operative complication will also be evaluated.
At Month 1 (D30), Month 6 (M6) and Month 12 (M12) investigator will realize phone visits in order to :
Get safety aspects related to antibiotic treatment and treatment-related failures at month 1, six months and one year, notably, secondary surgery and in ST group, a complication requiring anew general anaesthesia or possible post-operative complication, will be recorded.
Child activity evolution and parental absenteeism will also be recorded. AE and concomitant treatment will be recorded. A Cost-Utility analysis will be performed from the healthcare payer's perspective.This medico anlysis will need Direct medical costs collection based on security social system.
- Conditions
- Acute Uncomplicated Appendicitis
- Being tested
- Amoxi Clavulanate, appendicectomy
- Keywords
- surgery, antibiotics therapy, medico - economic analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amoxi ClavulanateDrug
children in the arm NOT
appendicectomyProcedure or surgery
children in usual care in arm Surgery
| Study group | Role | What they receive |
|---|---|---|
| Non Operative Treatment Group | Experimental | Children randomised in this group are treated by antibiotic therapy : 80mg/kg/day of amoxicillin for patients weighing less than 40 kg and 3 g/day for those weighing 40 kg or more)with a relay of Amoxicillin/clavulanic acid (80mg/kg/day for patients weighing less than 40 kg and 3 g/day for those weighing 40 kg or more) PO in 2 doses daily, for a total antibiotictreatment (IV and PO) of 7 days. Receives: Drug: Amoxi Clavulanate |
| Surgery Treatment Group | Other | Children randomised in this group the child will undergo appendectomy within 24 hours, according to surgical unit organization. No antibiotics will be administered before surgery. Receives: Procedure: appendicectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of treatment-related failures at one year
readmissions for suspicion of appendicitis, secondary surgery, emergency visits related to appendicitis management, postoperative infections, side effects of antibiotics, adverse events of anesthesia. In surgery group, a normal appendix based on pathology or a complication requiring a new general anaesthesia
Measured: 12 months
Secondary outcomes (6)
Initial success rate
Measured: Day 12
Score of quality of life with the questionnaire EQ-5D-Y-3L for children
0 is the worst score and 1 the better score (it is possible to have very bad values under 0)
Measured: Day 1, Month 1 and Month 12.
Score of of quality of life with the questionnaire EQ-5D-5L for parents
0 is the worst score and 1 the better score (it is possible to have very bad values under 0)
Measured: Day 1, Month 1 and Month 12.
Direct Medical costs, and indirect costs (parental absenteeism) descriptions
Measured: Month 12
Rehospitalization, appendectomy
Using consumption data available in SNDS database, describe child care pathways over 5 years
Measured: from Day 1 to Year 5
Incidence of adverse events
in the two groups, and incidence of adverse events due to antibiotics in the NOT group
Measured: At Month 1 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Uncomplicated AppendicitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 724 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier ABBO, Study director, University Hospital of Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07587450
- Sponsor's protocol ID
- RC31/24/0320
- Acronym
- NACAC
- Status last verified
- May 2026
- First submitted
- 7 May 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided