Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis

Herlev Hospital13 enrolled

Overview

The objective of this trial is to evaluate if intraoperative intraperitoneal administration of fosfomycin, metronidazole and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) followed by oral antibiotic for three days is as effective as the current intravenous antibiotic treatment given during and three days after appendectomy for perforated appendicitis. The primary outcome is the total length of hospital stay, defined as the number of hours in hospital after end of operation and until 30-day follow-up.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Appendicitis Perforated

Interventions

Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o.

All drugs will be administered together intraperitoneally at the end of the surgery after the appendix has been removed. Hereafter, the intervention group will receive three days of orally administered antibiotics: 500 mg amoxicillin combined with 125 mg clavulanic acid and 500 mg metronidazole. These doses will be administered three times daily.

Standard antibiotics intravenouslyDRUG

4 g piperacillin/500 mg tazobactam and 1 g metronidazole administered intravenously during surgery followed by 4 g piperacillin/500 mg tazobactam and 500 mg metronidazole administered intravenously three times daily for three days.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years * Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual laparoscopic appendectomy * Perforated appendicitis (diagnosed during surgery by the surgeon) * Negative p-HCG (women) * Written informed consent after written and verbal information (preoperatively for the intervention group and postoperatively for the control group) Exclusion Criteria: * Cannot understand, read or speak Danish * Previous allergic reaction to fosfomycin, metronidazole, rhGM-CSF, or penicillins e.g. piperacillin or amoxicillin * Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy or appendicitis without perforation * Other intra-abdominal pathology requiring surgical intervention at the same operation * Known renal or hepatic disease or biochemical evidence at the time of admission * Known hematologic disease in current medical treatment * American Society of Anesthesiologists (ASA) physical status ≥4 (a patient with severe systemic disease that is a constant threat to life) * Body weight \>110 kg * Surgery converted to open appendectomy * Anticipated compliance problems

Locations (2)

Department of Surgery, Bispebjerg Hospital

Copenhagen, Denmark

Department of Surgery, Herlev Hospital

Herlev, Denmark

Outcomes

Primary Outcomes

Total length of hospital stay

in hours

Time frame: From end of surgery until 30-days follow-up

Secondary Outcomes

Gastrointestinal Quality of Life Index (GIQLI)

A disease-specific questionnaire validated in Danish is collected at 10 days postoperatively (±2 days) and at 30 days postoperatively (±3 days)

Time frame: 10 days (±2 days) and 30 days (±3 days) postoperatively

Side effects

Number and description. A questionnaire regarding side effects is collected within the first 24 hours after surgery and at 10 days postoperatively (±2 days)

Time frame: Within 24 hours after surgery and 10 days (±2 days) postoperatively

Postoperative complications

Number. According to the Clavien-Dindo grading

Time frame: From end of surgery until 30-days follow-up

Surgical site infections requiring surgical drainage

It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC)

Time frame: From end of surgery until 30-days follow-up

Intraabdominal abscesses requiring drainage

Number. It is defined as an organ/space surgical site infection according to CDC

Time frame: From end of surgery until 30-days follow-up

Readmissions

Number. Only readmissions related to the surgery will be registered; e.g. admission and treatment of a non-related condition will not be registered.

Time frame: From end of surgery until 30-days follow-up

Reoperations

Number. Only reoperations related to the appendectomy will be registered.

Time frame: From end of surgery until 30-days follow-up

Time to return to normal activities

Time period in days. The date is defined at the time point at which the participant could return to normal daily activities.

Time frame: From end of surgery until 30-days follow-up

Period of sick leave "absence from work"

Time periode in days. The parameter is defined as the number of days from the operation to the time point at where the participant returned to work or school.

Time frame: From end of surgery until 30-days follow-up

Costs

The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups.

Time frame: From end of surgery until 30-days follow-up

Adverse events

Time frame: From end of surgery until 30-days follow-up

Microbiological flora and susceptibility

Number and type of positive specimens. If participants have a postoperative infectious complication.

Time frame: From end of surgery until 30-days follow-up