Appendicitis Perforated
Conditions
Brief summary
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.
Interventions
DRUGCombination 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.
DRUGStandard antibiotics intravenously
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.
Sponsors
Bispebjerg Hospital
Herlev Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Quasi-randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total length of hospital stay | From end of surgery until 30-days follow-up | in hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side effects | Within 24 hours after surgery and 10 days (±2 days) postoperatively | Number and description. A questionnaire regarding side effects is collected within the first 24 hours after surgery and at 10 days postoperatively (±2 days) |
| Postoperative complications | From end of surgery until 30-days follow-up | Number. According to the Clavien-Dindo grading |
| Surgical site infections requiring surgical drainage | From end of surgery until 30-days follow-up | It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC) |
| Intraabdominal abscesses requiring drainage | From end of surgery until 30-days follow-up | Number. It is defined as an organ/space surgical site infection according to CDC |
| Readmissions | From end of surgery until 30-days follow-up | Number. Only readmissions related to the surgery will be registered; e.g. admission and treatment of a non-related condition will not be registered. |
| Gastrointestinal Quality of Life Index (GIQLI) | 10 days (±2 days) and 30 days (±3 days) postoperatively | A disease-specific questionnaire validated in Danish is collected at 10 days postoperatively (±2 days) and at 30 days postoperatively (±3 days) |
| Time to return to normal activities | From end of surgery until 30-days follow-up | Time period in days. The date is defined at the time point at which the participant could return to normal daily activities. |
| Period of sick leave absence from work | From end of surgery until 30-days follow-up | 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. |
| Costs | From end of surgery until 30-days follow-up | The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups. |
| Adverse events | From end of surgery until 30-days follow-up | — |
| Microbiological flora and susceptibility | From end of surgery until 30-days follow-up | Number and type of positive specimens. If participants have a postoperative infectious complication. |
| Reoperations | From end of surgery until 30-days follow-up | Number. Only reoperations related to the appendectomy will be registered. |
Countries
Denmark
Outcome results
None listed