Patient Choice Between Antibiotics and Appendectomy in Uncomplicated Appendicitis (FRENCH 47 - ALACARTE)

Appendectomy provides definitive treatment for acute appendicitis. However, antibiotic therapy alone represents an alternative treatment option for patients with acute uncomplicated appendicitis.Patients are centrally randomized in a 1:1 ratio to either the "Patient Preference Treatment" group or the "Systematic Appendectomy" group.In the "Patient Preference Treatment" group, patients receive information through a video, followed by a discussion with the investigator and a reflection period of at least 30 minutes. Patients may then choose between antibiotic therapy alone and appendectomy. Patients who do not make a treatment choice undergo appendectomy.The study is based on the hypothesis that giving patients a choice of treatment could reduce treatment regret without compromising safety, particularly by not increasing the risk of complicated appendicitis.Treatment regret will be assessed one year after the randomization.

• Shared decision-making (Other): Participants receive standardized information and are then allowed to choose between antibiotic therapy alone and appendectomy. Patients who do not express a preference undergo appendectomy.
• amoxicillin-clavulanate (Drug), also known as amoxicillin-clavulanic acid: amoxicillin-clavulanate (PO or IV 1 gx3/day for patients <90 kg or 1 gx4/day for patients ≥90 kg)
• Appendectomy (Procedure): Appendectomy

Primary outcomes

• Regret about the initial treatment [12 month after the randomization]: The presence of regret about the initial treatment will be evaluated through a specific questionnaire completed online by the patient. The question will be: "You were initially treated for your appendicitis (infection of the appendix) either by surgery with removal of the appendix (appendectomy) or by antibiotic therapy alone without surgery initially. Do you regret the treatment you received? YES - NO." The surgeon will be blinded to the answer.

Secondary outcomes

• Patient's symptom persistence or recurrence [at 12 months]: Proportion of patients with at least one symptom persistence or recurrence at 12 months : Symptom persistence defined by participants who report the persistence of significant abdominal pain (≥4 with intensity quantified using the numeric pain rating scale from 0 to 10), the persistence of a perceived or measured fever > 38.0°C, or the persistence of chills.
• Patient's quality of life at 12 months. [at 12 months]: Quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). questionnaire using the French value set for scoring heath states and fulfilled by the participants (Responses are recorded on a 5-point scale: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, and 5 = extreme problems or unable to perform the activity.)
• Regret concerning the treatment received [at 12 months]: The regret at 12 months assessed by the validated decisional regret scale. This standardized scale allows quantifying treatment regret by a score ranging from 0 for no regret to 100 for maximum regret.
• Diagnosis of a complicated AA [within 12 months after randomization]: Complicated AA is defined by a localized or diffuse peritonitis, abscessed appendicitis, necrotized appendicitis or appendicular plastron as determined by the surgeon through intraoperative findings or through clinical examination and abdominal imaging (CT-scan or MRI or abdominal US) in case of non-surgical management.
• Positive bacteriological examination of intrabdominal fluid harvested during surgery [during surgery]
• Overall 12-months morbidity [12 months]: The occurrence of at least one of the following complication during the 12 months after randomization: site-related infectious complications (defined as incisional infections or organ-space infections \[abscesses\]), percutaneous drainage procedure, surgical intervention (for complication after appendectomy or appendectomy for recurrent appendicitis after antibiotic), ileus requiring the placement of a nasogastric tube, wound hernia, small bowel obstruction requiring emergency consultation or hospitalization, adverse event related to the known side effects of the administered antibiotic therapy.
• Unscheduled medical encounter [within 12 months after randomization]: by at least one of the following events: * Unscheduled consultations or readmissions at hospital related to the AA or to its treatment reported by the participant. * Among patients treated initially by appendectomy: proportion of patient with unscheduled surgical procedures due to delayed complications after appendicitis or appendectomy. * Among patients treated initially by antibiotics only: proportion of occurrence of appendectomy (with or without appendicitis on the surgical specimen) or unscheduled surgical procedure other than appendectomy due to complications related to the AA. * Among patients treated initially by antibiotics only: proportion of recurrence or persistent AA proven by pathological examination of the appendix after appendectomy or by an imaging (CT or ultrasound or MRI) in case of nonsurgical management.
• Diagnosis of an appendicular tumor [within 12 months after randomization]: Presence of an appendicular tumor (benign or malignant) defined by the anatomopathological diagnosis on the operative specimen of appendectomy.
• Cost per quality-adjusted life year (QALY) gained [at 12 months]: Economic evaluation comparing patients who had the option to select their treatment versus patients who underwent systematic appendectomy. Results will be expressed as cost per QALY gained at 12 months.
• Cost per additional patient without complication [at 12 months]: Economic evaluation comparing patients who had the option to select their treatment versus patients who underwent systematic appendectomy. Results will be expressed as cost per additional patient without complication at 12 months.

Other outcomes

• Patient's regret [at 1 and 6 months]: assessed by the answer at the question : " : "You were initially treated for your appendicitis (infection of the appendix) either by surgery with removal of the appendix (appendectomy) or by antibiotic therapy alone without surgery initially. Do you regret the treatment you received? YES - NO."
• Treatment regret assessed by the validated decisional regret scale. [at 1 and 6 months]: This standardized scale allows quantifying treatment regret by a score ranging from 0 for no regret to 100 for maximum regret.
• Persistence of appendicitis-related symptoms assessed by abdominal pain, fever, or chills [at 1 and 6 months]: Symptom's persistence defined by participants who report the persistence of a significant abdominal pain (≥4 with intensity quantified using the numeric pain rating scale from 0 to 10), the persistence of a perceived or measured fever > 38.0°C, or the persistence of chills.
• Patient's quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at 1 month and 6 months [at 1 and 6 months]: Quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). questionnaire using the French value set for scoring heath states and fulfilled by the participants (Responses are recorded on a 5-point scale: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, and 5 = extreme problems or unable to perform the activity.)
• Number of participants reporting each potential cause of treatment regret, assessed using a 13-item self-administered questionnaire [at 12 months]: Potential causes of treatment regret assessed using a 13-item self-administered questionnaire evaluating information and understanding before treatment, decision-making process, treatment experience, and social and economic consequences. Each item is scored from 1 (strongly agree) to 5 (strongly disagree).
• 12-month overall length of stay [within 12 months after the randomization]
• 12-month duration of sick leave related to the AA or to its treatment. [within 12 months after the randomization]
• Therapeutic adherence to the treatment (Among patients initially treated by antibiotics only) [at 1 month]: Among patients initially treated by antibiotics only: Therapeutic adherence to the treatment defined by the complete intake of the prescribed antibiotic doses over a duration of 7 days. This criterion will be assessed by the following question at 1 month: "Regarding the antibiotic treatment prescribed, have you?: 1) Taken all prescribed doses, 2) Missed some doses but at least 75% of the treatment was taken, 3) Missed some doses but between 25% and 75% of the treatment was taken, 4) Missed some doses with less than 25% of the treatment taken"
• Pain intensity at the time of the treatment decision assessed by the Numeric Pain Rating Scale (patient preference treatment group) [at inclusion]: Pain intensity on an 11-point Numeric Pain Rating Scale from 0 (no pain) to 10 (worst imaginable pain); higher scores indicate more pain. Presence or absence of fever, nausea and vomiting recorded at the same time.
• Main motivation for the treatment decision assessed by a self-administered questionnaire (patient preference treatment group) [at inclusion]: Self-administered questionnaire completed after the treatment decision: main reason for choosing antibiotic therapy alone or appendectomy (8 options), or for choosing not to decide (4 options).
• Decisional conflict assessed by the Decisional Conflict Scale (patient preference treatment group) [at inclusion]: 16-item validated Decisional Conflict Scale. Total score from 0 (no decisional conflict) to 100 (extremely high decisional conflict); higher scores indicate greater decisional conflict.
• Healthcare access and lifestyle assessed by a self-administered questionnaire (patient preference treatment group) [at 1 month]: Self-administered online questionnaire on travel time to the general practitioner and to the hospital, living conditions, occupational status, educational level, use of primary care and sources of health information.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Patients aged 18-70 years
2. Diagnosis of uncomplicated AA established by the investigator surgeon that relies on clinico-biological suspicion of acute AA confirm by care radiological tests (US and/or CT and/or MRI) including appendix diameter >6.0mm. and without:

   1. Diffuse peritonitis on clinical exam (i.e., rigid abdomen / four quadrant peritonitis);
   2. Radiologic findings of:

   i. Free air ii. Walled off fluid collection concerning for an abscess iii. Significant amounts of intra-abdominal fluid throughout abdomen (i.e.,more than trace fluid) iv. Extent of inflammation or adjacent organ involvement on radiologic, appendicular plastron on radiologic imaging
3. Surgery expected within 24 hours after diagnosis
4. Patient able to read and understand the language and content of the study documents and agreeing to adhere to the protocol requirements
5. Patient with internet access at home and a valid email address who declares being able to complete an online questionnaire
6. Signature of the written informed consent form by the patient
7. Affiliation to a French health insurance scheme

Exclusion Criteria:

Exclusion Criteria :

1. Appendicolith visible on radiological tests (US and/or CT and/or MRI)
2. Appendix diameter >15mm (risk factor of appendicular tumor) visible on radiological tests (US and/or CT and/or MRI)
3. Suspicion of a tumor of the appendix on the imaging exam ((US and/or CT and/or MRI) by the radiologist: (mucocele, pseudomyxoma, neuroendocrine tumor, adenocarcinoma of the appendix, another type of tumor…)
4. Evidence of severe sepsis or septic shock (e.g., new presumed sepsis-related organ dysfunction, elevated lactate, and/or fluid unresponsive hypotension)
5. Severe or uncontrolled comorbidities, such as hepatic cirrhosis, heart failure, acute or chronic kidney failure (estimated glomerular filtration rate <60mL/min), concurrent hemodialysis or peritoneal dialysis, or treatments using indwelling venous catheters, presence of active cancer or a malignant hemopathy, anticoagulant treatments
6. Recent (within 90 days) placement of surgical implant (e.g., pacemaker, joint prosthesis, mechanical valve) or indwelling Left Ventricular Assist Device
7. Immunodeficiency (e.g., absolute neutrophil count <500/mm3, chronic immunosuppressive drugs, long term corticosteroids, or known AIDS \[CD4 count <200/mm3 or AIDS-defining illness assessed by patient history)
8. History of inflammatory bowel disease (Crohn disease, or ulcerative colitis or indeterminate colitis)
9. Ongoing antibiotic therapy for another infection
10. Abdominal/pelvic surgery in the past month
11. Hypersensitivity to Amoxicillin, clavulanic acid and penicillins
12. History of severe immediate hypersensitivity reaction (e.g., anaphylaxis) to another beta-lactam (e.g., a cephalosporin, carbapenem, or monobactam).
13. History of icterus/liver damage related to amoxicillin/clavulanic acid
14. Allergy to any of the excipients listed in section 6.1 of SmPC
15. History of AA treated by antibiotics or appendectomy
16. Pregnant* or breast-feeding women
17. Participation in another interventional study or being in the exclusion period at the end of a previous study.
18. Mental or cognitive impairment rendering the patient unable to understand study information or to provide informed consent.
19. Patient being a relative of the investigator or of a member of the research team directly involved in the trial (assistant doctors, pharmacists, nurses, or study coordinators).
20. Adult under guardianship or deprived of freedom

• Maxime COLLARD, Principal investigator, APHP

NIH grants: 2025