Pragmatic Randomized Trial of Patient‑Driven Choice (Oral Amoxicillin/Clavulanic Acid vs Appendectomy) vs Systematic Appendectomy in Uncomplicated Acute Appendicitis

The primary objective is to determine whether offering patients with uncomplicated acute appendicitis a choice between antibiotic therapy and appendectomy reduces treatment regret at 12 months compared with a policy of systematic appendectomy, thereby assessing the impact of shared decision‑making on patient satisfaction. Secondary objectives address additional clinical and economic outcomes:

• Efficacy – comparison of symptom persistence or recurrence at 12 months, quality of life at 12 months, and quantitative assessment of treatment regret using the decision regret scale at 12 months;
• Safety – comparison of the incidence of complicated appendicitis within 12 months, positive bacteriological findings from intra‑abdominal fluid, overall 12‑month morbidity, unscheduled medical encounters, and diagnosis of an appendiceal tumor within 12 months;
• Economic evaluation – cost‑effectiveness analysis of the patient‑driven treatment option versus systematic appendectomy.

The trial enrolled adult patients aged 18–70 years diagnosed with uncomplicated acute appendicitis based on clinical suspicion confirmed by ultrasonography, CT, or MRI showing an appendix diameter > 6 mm without diffuse peritonitis, free air, abscess, significant intra‑abdominal fluid, or adjacent organ involvement. Both female and male individuals were eligible. Inclusion required ability to read and understand study documents, internet access with a valid email for online questionnaires, affiliation with a French health‑insurance scheme, and provision of written informed consent. Surgery was expected within 24 hours of diagnosis. General health status was limited to the absence of severe intra‑abdominal infection or widespread peritonitis. Lifestyle factors such as specific diet or physical‑activity restrictions were not stipulated. The sponsor did not provide information on the total number of participants.

The study is a phase 4 pragmatic randomized trial evaluating management of adult patients with uncomplicated acute appendicitis diagnosed by clinical assessment and imaging; eligible individuals are aged 18–70 years, have no diffuse peritonitis or abscess, and are scheduled for surgery within 24 hours. After an initial screening visit to confirm eligibility and obtain written informed consent, participants are allocated to either a patient‑driven choice arm, permitting selection of oral amoxicillin/clavulanic acid (4 g per day) or immediate appendectomy, or to a systematic appendectomy arm. The primary endpoint, assessed at the 12‑month visit, is the presence of treatment regret regarding the initial therapy, with secondary outcomes including symptom persistence or recurrence, health‑related quality of life (EQ‑5D‑5L), and a validated decisional regret scale. Follow‑up visits are scheduled at 30 days, 6 months, and 12 months after treatment initiation, culminating in an end‑of‑study visit at 12 months; the total duration of participant involvement therefore spans approximately one year from randomization. Recruitment is planned to commence on 1 April 2026 and conclude on 31 May 2029.

The investigational regimen consists of a fixed‑dose combination of amoxicillin sodium and clavulanic acid supplied as oral tablets (pharmaceutical form code PHF00231MIG). Each administered dose contains a total of 4 g of active ingredients and is given by mouth according to the schedule defined in the protocol.

Amoxicillin sodium provides the β‑lactam antibacterial component of the combination. It is delivered in the oral tablet formulation described above.

Clavulanic acid acts as a β‑lactamase inhibitor, enhancing the activity of amoxicillin against β‑lactamase‑producing organisms. It is co‑formulated with amoxicillin sodium in the same tablet.

The comparator treatment is standard surgical management. Participants assigned to the systematic‑appendectomy arm undergo an open or laparoscopic appendectomy performed by the treating surgeon according to local practice.

Administration of the oral regimen is recorded in the study log, and compliance is assessed by pill count and patient diary review at each follow‑up visit.

Efficacy will be evaluated using predefined endpoints. The primary endpoint is the presence of regret about the initial treatment one year after initiation, assessed by a single yes/no question. Secondary endpoints include the proportion of patients with symptom persistence or recurrence at 12 months, health‑related quality of life at 12 months measured with the EQ‑5D‑5L questionnaire using the French value set, and treatment regret quantified by the validated decisional regret scale (score 0–100). The study population consists of adult patients diagnosed with uncomplicated acute appendicitis.

All efficacy assessments will be performed at the 12‑month follow‑up visit. The regret question and decisional regret scale will be self‑administered by participants. Symptom persistence or recurrence will be captured through patient‑reported outcomes. The EQ‑5D‑5L questionnaire will be completed by participants to generate an index score. The primary outcome will be reported as the proportion of participants answering “YES” to the regret question. Secondary outcomes will be expressed as the proportion with symptom persistence/recurrence, mean EQ‑5D‑5L index values, and mean decisional regret scores. Comparative analyses between the patient‑driven choice arm and the systematic appendectomy arm will employ chi‑square tests for categorical data and t‑tests or appropriate non‑parametric methods for continuous variables.