Evaluation of Postoperative Antibiotic Therapy with Metronidazole, Ceftriaxone, and Ofloxacin in Complicated Acute Appendicitis: A Phase III Non-Inferiority Study
- Trial ID
- 2024-515834-34-00
- Protocol
- PI2017_843_0002
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this 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 complicated acute appendicitis (CAA), excluding cases of generalized peritonitis. This is clinically relevant as it aims to determine whether withholding antibiotics post-surgery could maintain similar infection rates, potentially reducing unnecessary antibiotic use and its associated risks.
Participants
The clinical trial focuses on patients diagnosed with **complicated acute appendicitis** (CAA), excluding cases of generalized peritonitis. The study population includes both male and female participants aged 18 and over, with no vulnerable populations selected. Participants must have undergone a laparoscopic appendectomy and have CAA confirmed peroperatively by the presence of a perforated appendicitis, extraluminal fecaliths, abscesses, and/or localized peritonitis. The trial aims to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection rate. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that only individuals who have signed an informed consent form (ICF) are included in the study.
Plans and Procedures
The clinical trial is designed to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection (SSI) rate in patients with **complicated acute appendicitis** (CAA), excluding cases of generalized peritonitis. This is a prospective, randomized, open-label, non-inferiority Phase III study. The trial will involve a comparison between patients receiving standard post-operative antibiotic therapy and those who do not, following laparoscopic appendectomy. The study is expected to run from October 2018 to November 2026, with the primary endpoint being the proportion of patients with deep SSIs by post-operative day 30 (POD30).
Participants will be randomly assigned to either the treatment or control group. The trial will include several study visits: an initial screening visit to confirm eligibility, which requires a diagnosis of CAA confirmed peroperatively, laparoscopic appendectomy, age 18 or over, and a signed informed consent form. Follow-up visits will occur at regular intervals to monitor the patient's recovery and collect data on infection rates, quality of life, and other secondary endpoints. The end-of-study visit will occur at POD30, where final assessments will be made.
The expected length of participant involvement is approximately 30 days post-surgery. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that necessitate discontinuation of participation. The study aims to provide valuable insights into the necessity of post-operative antibiotics in preventing SSIs in patients with CAA, potentially influencing future treatment guidelines.
Treatment
The clinical trial involves the administration of several **experimental medications** and a non-experimental treatment. The first experimental medication is a combination of **metronidazole** and glucose, administered via infusion. The pharmaceutical form is designated as PHF00230MIG. The maximum daily dose is 1500 mg, with a total maximum dose of 4500 mg over a treatment period of up to 3 days. This medication is used as a comparator in the study.
The second experimental medication is a combination of **ceftriaxone sodium** and lidocaine hydrochloride, also administered via infusion. The pharmaceutical form is PHF00231MIG. The maximum daily dose is 2 g, with a total maximum dose of 6 g over a 3-day treatment period. This medication serves as a comparator in the trial.
The third substance used in the study is **sodium chloride**, which acts as the test treatment. It is administered via infusion in a pharmaceutical form identified as PHF00169MIG. The maximum daily dose is 0.9%, with a total maximum dose of 2.7% over a 3-day period.
The fourth experimental medication is **ofloxacin hydrochloride**, administered via infusion. The pharmaceutical form is PHF00230MIG. The maximum daily dose is 500 mg, with a total maximum dose of 1500 mg over a 3-day treatment period. This medication is used as a comparator in the study.
All medications are administered via the infusion route, and participant compliance is monitored throughout the trial. The study aims to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection rate in patients with complicated acute appendicitis, excluding cases of generalized peritonitis.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of patients with deep **Surgical Site Infections (SSIs)** by post-operative day 30 (POD30). Deep SSIs are defined according to the Centers for Disease Control and Prevention (CDC) criteria as infections occurring within 30 days of surgery, related to the surgery, affecting the organ or cavity around the surgical site, and exhibiting at least one sign as defined in the protocol.
Secondary endpoints include several measures: quality of life assessed using the SF36 questionnaires prior to surgery and upon discharge, the proportion of patients with superficial SSIs, post-operative infection rates by POD30 including SSIs and remote infections, and the number of antibiotic-free days between randomization and POD30. Additionally, the study will evaluate the microbial flora from per-operative samples, the balance between antibiotic therapy and microbial resistance, morbidity and mortality according to the Dindo-Clavien classification, length of stay (LOS) defined as the number of days of hospitalization between surgery and discharge, and the rehospitalization rate during the study period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- CAA confirmed peroperatively by the presence of a perforated appendicitis, extraluminal fecaliths, abscesses and/or localized peritonitis (pus in one or two abdominal quadrants out of four: upper left, upper right, lower left or lower right). Actually, there is no official definition of what a localized CAA is, however Ross (J.Ross. Secondary peritonitis: principles of diagnosis and intervention, BMJ. 2018; 361) define localized peritonitis as infection to one or two quadrants out of four (upper left, upper left, lower left or lower right)
- Laparoscopic appendectomy
- Aged 18 or over
- signed ICF
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)
- other diseases (Crohn’s disease, ulcerative colitis, treatment with an immunosuppressive therapy)
- Severe sepsis, septic shock or generalized peritonitis.
- a) A decision to perform open appendectomy.
- b) 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
- d) 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)
- e) 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
- Living at more than one hour from an hospital
- b) 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
- 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 out of four).
- Pregnancy or breastfeeding.
- Patient under guardianship
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 22 Oct 2018 | 1494 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
METRONIDAZOLE | Comparator | PHF00230MIG | INFUSION | 1500 | 3 | SCP1153368 |
CEFTRIAXONE | Comparator | PHF00231MIG | INFUSION | 2 | 3 | SCP107121969 |
SODIUM CHLORIDE | Test | PHF00169MIG | INFUSION | 0.9 | 3 | SCP12712712 |
LEVOFLOXACIN | Comparator | PHF00230MIG | INFUSION | 500 | 3 | SCP111060923 |