Clinical trial NCT03435900: Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis
Official title: Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Conventional Antibiotics for Perforated Appendicitis - a Pivotal Quasi-randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Appendicitis Perforated
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
First posted: 2018-02-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Quasi-randomised controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Total length of hospital stay
timeFrame: From end of surgery until 30-days follow-up
Secondary outcomes:
measure: Gastrointestinal Quality of Life Index (GIQLI)
timeFrame: 10 days (±2 days) and 30 days (±3 days) postoperatively
measure: Side effects
timeFrame: Within 24 hours after surgery and 10 days (±2 days) postoperatively
measure: Postoperative complications
timeFrame: From end of surgery until 30-days follow-up
measure: Surgical site infections requiring surgical drainage
timeFrame: From end of surgery until 30-days follow-up
measure: Intraabdominal abscesses requiring drainage
timeFrame: From end of surgery until 30-days follow-up
measure: Readmissions
timeFrame: From end of surgery until 30-days follow-up
measure: Reoperations
timeFrame: From end of surgery until 30-days follow-up
measure: Time to return to normal activities
timeFrame: From end of surgery until 30-days follow-up
measure: Period of sick leave "absence from work"
timeFrame: From end of surgery until 30-days follow-up
measure: Costs
timeFrame: From end of surgery until 30-days follow-up
measure: Adverse events
timeFrame: From end of surgery until 30-days follow-up
measure: Microbiological flora and susceptibility
timeFrame: From end of surgery until 30-days follow-up
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Surgery, Bispebjerg Hospital
city: Herlev
country: Denmark
facility: Department of Surgery, Herlev Hospital
Study officials:
References:
citation: Fonnes S, Roepstorff S, Holzknecht BJ, Olesen CS, Olsen JHH, Schmidt L, Alder R, Gamborg S, Rasmussen T, Arpi M, Jorgensen LN, Rosenberg J. Shorter Total Length of Stay After Intraperitoneal Fosfomycin, Metronidazole, and Molgramostim for Complicated Appendicitis: A Pivotal Quasi-Randomized Controlled Trial. Front Surg. 2020 May 5;7:25. doi: 10.3389/fsurg.2020.00025. eCollection 2020.