Appendectomy Versus Conservative Treatment for Uncomplicated Acute Appendicitis

Study Overview
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Brief Summary
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On September the 15th, 2015, Italian surgeons, radiologists and pathologists with a special interest and expertise in the diagnosis and management of Acute Appendicitis (AA), met up under the auspices of the Italian Society of Hospital Surgeons (ACOI) in Oristano (Italy) to constitute the ACTUAA collaborative working group. The main objectives of the working group are: To create a working basis for analyzing the diagnostic features, treatment modalities and outcomes of interest of both the antibiotic-first approach and appendectomy for patients with uncomplicated AA. To investigate the clinical, laboratory and radiologic modalities adopted for the diagnosis To determine the outcomes of patients treated with antibiotics or appendectomy in the short and long term periods. To compare results according to the type of intervention. To stratify the risk of recurrence for patients treated with antibiotics according to clinical, laboratory and radiology findings. To evaluate the sensibility and specificity of clinical and laboratory scores for the diagnosis of uncomplicated AA. To identify a subgroup of patients with uncomplicated AA for whom antibiotic treatment can be highly effective. General study design The study protocol is designed according to the SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. The study period is estimated to be of 12 month + 12 month of follow-up (with a second session of follow-up following 5-years), beginning on 01/04/2017. Participants All adult patients (aged over 18 years old) with suspected AA will be admitted to the Surgical Department of the nine participating Italian hospitals, where they will be studied carefully by the on call surgeon. Patients will be then informed of the study protocol and invited to give written consent for participation and for sensible data collection for scientific purposes. Subsequently, only patients who will undergo diagnostic imaging (as specified later) and from whom a written informed consent will be obtained, can be enrolled in the study and registered by each Center using a uniform electronic registration form and database. General characteristics, medical history, clinical findings, physical investigation, and blood tests will be reported in the medical record. Pain will be quantified by Visual Analogue Scale (VAS) scoring system before administrating any pain medications and after the treatments. In order to enter the study, patients will have to undergo diagnostic imaging (US and/or CT scan or MRI scan) and only the diagnosis of uncomplicated AA confirmed by diagnostic imaging will permit patient enrollment in the study. Specific aims of the ACTUAA Study The objective of this prospective non-randomized controlled, multicenter, multidisciplinary trial is to compare the antibiotic therapy and emergency appendectomy for the treatment of patients with uncomplicated AA(without abscess or free perforation), confirmed by US and/or CT or MRI scan. No changes in the daily practice regarding the diagnostic, clinical and treatment pathways will be required to the participating centers. However, only the patients with uncomplicated AA, confirmed by one of the above mentioned radiologic tools will be enrolled in the study. The decision on which of the tools are to be adopted will be up to the local lead surgeon. Primary Outcome Measure: Number of participants with complication-free treatment success, defined as success of the initial treatment with uncomplicated course. Secondary Outcome Measures: Length of hospital stay; Pain evaluation; Time to return to normal activity; Period of sick-leave; Complicated appendicitis with peritonitis identified at the time of surgical operation; Quality of life as assessed by the Short Form 12-scale (SF-12)

Official Title
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A Prospective Non-randomized Controlled, Multicenter, Multidisciplinary Trial Comparing Appendectomy and Conservative Treatment for Patients With Uncomplicated Acute Appendicitis (the ACTUAA STUDY).

Conditions
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Acute Appendicitis, Appendicitis Recurrent, Appendectomy, Antibiotic Therapy

Intervention / Treatment
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* Procedure: Laparoscopic or Open appendectomy
* Drug: Antibiotic-first therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age over 18 years Uncomplicated AA confirmed by US and/or CT or MRI scan. Exclusion Criteria: Pregnancy or lactating Diffuse peritonitis at physical examination Serious systemic illness Positive anamnesis for Inflammatory Bowel Disease (IBD)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients submitted to appendectomy as first-line treatment<br>Open or Laparoscopic Appendectomy The assignment of each patient to either the antibiotic-first management arm or the immediate surgery arm, will be non-randomized and decided independently by the Staff Specialist Surgeon on Call, upon careful assessment of AIR score, laboratory findings and imaging. The decision of the management pathway will not be influenced in any case by the participation of the patient in the study, and the assignment of the treatment will be decided by the consultant surgeon according to current good surgical practice and standard practice patterns in Italy. | Procedure: Laparoscopic or Open appendectomy<br>* Laparoscopic three-port or single-port appendectomy; or conventional McBurney laparotomic appendectomy; or open appendectomy performed through midline incision<br>|
| Patients treated with antibiotic-first strategy<br>Antibiotic therapy.maging. Patients managed conservatively will receive one of the following parenteral antibiotic treatments: Piperacillin/Tazobactam (4.5 g) three intravenous administration per day; Ceftriaxone (2 g) once per day or Ciprofloxacin (500 mg) twice per day plus Metronidazole (500 mg) three times per day; Amoxicillin/Clavulanic acid (2 g) four times per day for a length depending on the clinical conditions; Ertapenem (1 g) one administration per day for three days. Patients were discharged with oral antibiotics (amoxicillin/clavulanic acid or ciprofloxacin) for at least four days. | Drug: Antibiotic-first therapy<br>* Patients treated with antibiotics as first-line approach<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complication-free treatment success, as assessed by the Dindo-Clavien Scale. | Number of participants with complication-free treatment success, defined as success of the initial treatment with uncomplicated course: no postoperative complications, adverse events, or treatment failure occurring, as assessed by the Dindo-Clavien Classification. Post-treatment abdominal abscess, bowel occlusion, incisional hernia, pulmonary embolism, cardio-vascular complications, surgical site infection, complications due to anesthesia, adverse reactions to antibiotics. Complications are analyzed both for patients submitted to appendectomy and for those treated with surgery as second line approach, after primary antibiotic treatment failure. For patients treated with antibiotics, treatment failure (persistency and recurrence rates of acute appendicitis) will be evaluated within the overall-complications rate. Specific sub-analyses of the complications will be carried out. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Length of post-operative hospital stay for patients submitted to appendectomy; length of hospital stay for patients treated with antibiotics | 1 week | 
| VAS-Score | Pain evaluation performed through the visual analogue scale both for patients who undergo an appendectomy and for those treated with antibiotics | 1 month | 
| Time to return to normal activity | Time to return to normal activity both for patients who undergo an appendectomy and for those treated with antibiotics | 1 month | 
| Period of sick-leave | Period of sick-leave, intended as absence from work | 1 month | 
| Complicated appendicitis with peritonitis identified at the time of surgical operation. | In the antibiotic group the analysis will be carried out within the cohort of patients who will undergo appendectomy after the failure of the antibiotic therapy in order to assess whether or not a major risk of perforated appendicitis exists for patients who will be treated firstly with antibiotics. | 1 year | 
| Quality of life as assessed by the Short Form 12-scale (SF-12) | Quality of life estimated by the Short Form 12-scale (SF-12) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Appendicitis, Uncomplicated Acute Appendicitis, Appendectomy, Conservative Treatment, Antibiotic-first Treatment, Recurrent Appendicitis, Prospective Study