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

NCT03046758 | Completed Phase 2

• 1 other identifier: HEH-SF-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Appendicitis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Until 24 hours after surgery ±4 hours.

Secondary Outcomes (12)

• Main trial (14 patients): Biochemical markers

  4 hours ±30 minutes postoperatively.

• Main trial (14 patients): Blood pressure

  Until 12 hours ±30 minutes.

• Main trial (14 patients): Pulse

  Until 12 hours ±30 minutes.

• Main trial (14 patients): Frequency of respiration

  Until 12 hours ±30 minutes.

• Main trial (14 patients): Peripheral saturation

  Until 12 hours ±30 minutes.

Study Arms (1)

Participants

EXPERIMENTAL

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

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.

Participants

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Herlev Hospital: lead
• Jacob Rosenberg (Sponsor): collaborator
• Barbara Juliane Holzknecht (Investigator): collaborator
• Magnus Arpi (Investigator): collaborator
• Johan Juhl Weisser (Partner, data analysis): collaborator

Study Sites (1)

Department of Surgery, Herlev Hospital

Herlev, 2730, Denmark

Location

Related Publications (1)

• 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.

  PMID: 31040341 RESULT

Related Links

• Link to the article regarding the safety (open access)

MeSH Terms

Conditions

Appendicitis

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Siv Fonnes, MD

  Center for Perioperative Optimization, Department of Surgery, Herlev Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 8, 2017
• Study Start: February 24, 2017
• Primary Completion: December 7, 2017
• Study Completion: December 7, 2017
• Last Updated: May 29, 2019

Record last verified: 2019-05

Locations

DK (1)