Clinical trial NCT03688295: The Value of Post-operative Antibiotic Therapy After Laparoscopic Appendectomy for Complicated Acute Appendicitis (Other Than for Generalized Peritonitis)
Official title: The Value of Post-operative Antibiotic Therapy After Laparoscopic Appendectomy for Complicated Acute Appendicitis (Other Than for Generalized Peritonitis): a Prospective, Randomized, Placebo-controlled Phase III Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Complicated Acute Appendicitis
Keywords: complicated acute appendicitis
post-operative antibiotic therapy
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2018-09-28
Enrollment: 1476
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Around 30% of appendectomies are performed for complicated acute appendicitis (CAA, i.e. cases with perforated appendicitis, extraluminal fecaliths, abscesses, or local or generalized peritonitis). The treatment of these complicated forms involves the following steps: initiation of antibiotic treatment at the time of the diagnosis, appendectomy and post-operative antibiotic therapy that continues for 3 days for localized forms of CAA and for 5 days for generalized peritonitis (according to the guidelines issued by the French Society for Anaesthesia and Critical Care Medicine (SFAR)). The results of a Cochrane meta-analysis published in 2005 suggested that the post-operative infection rate was lower in patients having receiving antibiotic therapy after surgery for AA. When only cases of CAA were considered, the difference was no longer significant. However, it should be noted that the studies included in the meta-analysis are now rather old (published before 1995, with open procedures) and no longer provide valid data for answering this question because most appendectomies (80%) are now performed using laparoscopy. Furthermore, a recent cohort study compared a short (3-day) course of antibiotics with a long course (at least 5 days) in patients with CAA having undergone laparoscopic or open appendectomy. There was no significant intergroup difference in the post-operative complication rate. One can thus legitimately question whether post-operative antibiotic therapy is required after laparoscopic appendectomy for CAA.

The purpose of the present study is to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection (SSI) rate in patients presenting with CAA (other than cases of generalized peritonitis) by comparing a group of patients having undergone a conventional strategy of post-operative antibiotic therapy for three days after appendectomy for CAA (the control group) with a group of patients having received a post-operative placebo for three days after appendectomy for CAA (the experimental group). The primary endpoint will be evaluated at one month after randomization.


Eligibility criteria: Inclusion Criteria:

1. CAA suspected pre-operatively through a Saint-Antoine score ≤3 and confirmed peroperatively by the presence of a perforated appendicitis, extraluminal fecaliths, abscesses and/or localized peritonitis (pus in one or two abdominal quadrants).
2. Laparoscopic appendectomy.
3. Aged 18 or over
4. Written, informed consent

Exclusion Criteria:

1. Pre-operative exclusion criteria:

   * Patients with cardiac valvulopathy
   * Immunodepressed patients
   * Diabetic patients
   * Patients who have received an antibiotic treatment within 3 months before the surgery (and having a potential impact on the intestinal flora)
   * Related to the diagnosis: other diseases (Crohn's disease, ulcerative colitis, treatment with an immunosuppressive therapy).
   * Related to the severity of the appendicitis:
   * A Saint-Antoine score of 4 or 5 (non-complicated acute appendicitis)
   * Severe sepsis, septic shock, generalized peritonitis
   * Related to the treatment:

     * A decision to perform open appendectomy.
     * Patients who received an adaptive dose of Levofloxacine 250 mg/24H instead of 500 mg/24H in pre-operative or in per-operative (notably for patients with creatinine clearance ≤ 50 ml/min)
     * allergy to metronidazole or to one of the excipient
     * Contra-indication to the use of ceftriaxone (hypersensibility to the active substance, to another cephalosporin, to the excipient of the used speciality), history of severe hypersesibility (as anaphylactic shock), history of hypersensibility to another antibiotic of the beta-lactamin family (penicillin, monobactam, carbapénèmes)
     * Contra-indication to the use of levofloxacin, hypersensibility to levofloxacin, to another quinolone or to the excipient of one of the use speciality, hypersensibility to levofloxacine ou any other quinolone or to any excipient, epilepsia, history of tendinitis when injection of fluoroquinolones.
   * Related to the patient

     * Living at more than one hour from an hospital
     * Patient who has no relative or other third person who could be present at home and provide assistance in case of any problem for the discharged patient
2. Per-operative exclusion criteria (related to the severity of appendicitis):

   * Non-complicated forms (catarrhal appendicitis or the absence of extraluminal fecaliths, abscess or peritonitis).
   * Generalized purulent or stercoral peritonitis (the presence of pus or faeces in more than two quadrants of the abdomen).

In order to assess the reproducibility of the inclusion criteria in the various centres and to avoid variations due to the lack of an official definition for localized peritonitis, all centres will receive a video tutorial on localized peritonitis before the start of the study.

* Pregnancy or breastfeeding.
* Patients under guardianship.
* Patients unable to provide informed consent.
* Patient lacking social security coverage
* Allergy to metronidazole

Primary outcomes:
measure: proportion of patients having developed organ space surgical site infections (SSIs) by postoperative day (POD)30
timeFrame: postoperative day 30
Secondary outcomes:
measure: Quality of life post surgery using the 36-Item Short Form Health Survey
timeFrame: day 0 and day 30
measure: proportion of patients with superficial SSIs
timeFrame: postoperative day 30
measure: post-operative infection rates
timeFrame: postoperative day 30
measure: number of antibiotic-free days
timeFrame: postoperative day 30
measure: Description of the microbial flora
timeFrame: Day 0
measure: balance between antibiotic therapy and microbial resistance
timeFrame: postoperative day 30
measure: Evaluation of morbidity and mortality
timeFrame: postoperative day 30
measure: Length of hospital stay
timeFrame: postoperative day 30
measure: rehospitalization rate
timeFrame: postoperative day 30
Other outcomes:
Locations:
city: Amiens
country: France
facility: Amiens North Hospital
Study officials:
References:
citation: Sabbagh C, Siembida N, Dupont H, Diouf M, Schmit JL, Boddaert S, Regimbeau JM. The value of post-operative antibiotic therapy after laparoscopic appendectomy for complicated acute appendicitis: a prospective, randomized, double-blinded, placebo-controlled phase III study (ABAP study). Trials. 2020 Jun 1;21(1):451. doi: 10.1186/s13063-020-04411-1.