Clinical trial NCT03046758: The Safety and Pharmacokinetics of Intraperitoneal Administration in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
Official title: The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Appendicitis
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Jacob Rosenberg (Sponsor)
name: Barbara Juliane Holzknecht (Investigator)
name: Magnus Arpi (Investigator)
name: Johan Juhl Weisser (Partner, data analysis)
First posted: 2017-02-08
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to evaluate the safety of the intraperitoneal administration of the combination of fosfomycin, metronidazole, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients undergoing surgery for uncomplicated appendicitis. Further, in a sub-trial the aim is to investigate the plasma concentrations of fosfomycin and metronidazole after intraperitoneal administration.


Eligibility criteria: Inclusion Criteria:

* Men ≥18 years old
* Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual appendectomy
* Written informed consent after written and verbal information

Exclusion Criteria:

* Cannot understand, read or speak Danish
* Previous allergic reaction to fosfomycin, metronidazole, or GM-CSF
* Perforated appendicitis (diagnosed either during surgery or at a preoperative computer tomography (CT) scan)
* Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy
* Other intra-abdominal pathology requiring surgical intervention (diagnosed either during surgery or at a preoperative CT-scan)
* Known renal or hepatic disease or biochemical evidence at the time of admission
* Known autoimmune disease or other chronic inflammation
* Known hematologic disease or cancer
* Previous abdominal surgery (either laparoscopic or open surgery)
* Daily use or use of medication one week prior to or during the trial period apart from painkillers such as paracetamol, ibuprofen, tramadol, and morphine as well as drugs needed for anaesthesia, thrombosis prophylaxis, and nausea. Limitations for antibiotics are defined below
* Use of other antimicrobial agents than the trial treatment one month before until 24 hours after the trial treatment
* Participant in another drug trial one month prior to the date of the surgery
* Body mass index ≥35 kg/m2
* Weekly intake of alcohol \>14 units, where one unit corresponds to 12 g alcohol

Primary outcomes:
measure: Main trial (14 patients): Drop of white blood cell counts
timeFrame: 4 hours (± 30 minutes)
measure: Sub-trial (8 patients): The pharmacokinetics of fosfomycin.
timeFrame: Until 24 hours after surgery ±4 hours.
Secondary outcomes:
measure: Main trial (14 patients): Biochemical markers
timeFrame: 4 hours ±30 minutes postoperatively.
measure: Main trial (14 patients): Blood pressure
timeFrame: Until 12 hours ±30 minutes.
measure: Main trial (14 patients): Pulse
timeFrame: Until 12 hours ±30 minutes.
measure: Main trial (14 patients): Frequency of respiration
timeFrame: Until 12 hours ±30 minutes.
measure: Main trial (14 patients): Peripheral saturation
timeFrame: Until 12 hours ±30 minutes.
measure: Main trial (14 patients): Temperature
timeFrame: Until 12 hours ±30 minutes.
measure: Main trial (14 patients): Length of stay.
timeFrame: Until 30 days postoperatively.
measure: Main trial (14 patients): Length of stay.
timeFrame: Until 30 days postoperatively.
measure: Main trial (14 patients): Side effects
timeFrame: 10 days postoperatively ±1 day.
measure: Main trial (14 patients): Adverse events
timeFrame: Until 30 days postoperatively.
measure: Sub-trial (8 patients): The pharmacokinetics of metronidazole.
timeFrame: Until 24 hours after surgery ±4 hours.
measure: Sub-trial (8 patients): Microbiological flora and susceptibility
timeFrame: Until 30 days postoperatively.
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Department of Surgery, Herlev Hospital
Study officials:
affiliation: Center for Perioperative Optimization, Department of Surgery, Herlev Hospital
name: Siv Fonnes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fonnes S, Holzknecht BJ, Arpi M, Rosenberg J. Intraperitoneal administration of fosfomycin, metronidazole, and granulocyte-macrophage colony-stimulating factor in patients undergoing appendectomy is safe: a phase II clinical trial. Sci Rep. 2019 Apr 30;9(1):6727. doi: 10.1038/s41598-019-43151-4.