The Safety and Pharmacokinetics of Intraperitoneal Administration in Patients Undergoing Appendectomy for Uncomplicated Appendicitis

Herlev Hospital14 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Appendicitis

Interventions

A combination of fosfomycin, metronidazole and GM-CSF i.p.DRUG

All drugs will be administered together intraperitoneally at the end of the surgery after the appendix has been removed.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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

Locations (1)

Department of Surgery, Herlev Hospital

Herlev, Denmark

Outcomes

Primary Outcomes

Main trial (14 patients): Drop of white blood cell counts

The safety of intraperitoneal administration is evaluated through the white blood cell counts 4 hours (± 30 minutes) postoperatively. A toxic effect is defined by a drop below the lower reference range.

Time frame: 4 hours (± 30 minutes)

Sub-trial (8 patients): The pharmacokinetics of fosfomycin.

The plasma concentrations of fosfomycin over time are measured with high-performance liquid chromatography mass spectrometry (HPLC-MS) until 24 hours after surgery ±4 hours.

Time frame: Until 24 hours after surgery ±4 hours.

Secondary Outcomes

Main trial (14 patients): Biochemical markers

A standard panel of blood samples (e.g. white blood cell differential count, inflammation marker C-reactive protein (CRP), kidney function tests, liver function tests, and electrolytes) are analysed at admission (baseline) and 4 hours ±30 minutes postoperatively, these markers are compared.

Time frame: 4 hours ±30 minutes postoperatively.

Main trial (14 patients): Blood pressure

Blood pressure in mmHg is measured perioperatively (baseline, 5 minutes, 10 minutes and 15 minutes after the trial treatment has been administered) and postoperatively (4 and 12 hours ±30 minutes after the trial treatment has been administered).

Time frame: Until 12 hours ±30 minutes.

Main trial (14 patients): Pulse

Pulse in beats per minute is measured perioperatively (baseline, 5 minutes, 10 minutes and 15 minutes after the trial treatment has been administered) and postoperatively (4 and 12 hours ±30 minutes after the trial treatment has been administered).

Time frame: Until 12 hours ±30 minutes.

Main trial (14 patients): Frequency of respiration

Data from ClinicalTrials.gov

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