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Completed

NCT Number: NCT03046758

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

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.

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Key information

Conditions

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

Age range

18 year–100 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Department of Surgery, Herlev Hospital

Herlev, 2730, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

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

    Time frame: 4 hours (± 30 minutes)

    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.

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

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

    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.

Secondary outcomes

  1. Main trial (14 patients): Biochemical markers

    Time frame: 4 hours ±30 minutes postoperatively.

    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.

  2. Main trial (14 patients): Blood pressure

    Time frame: Until 12 hours ±30 minutes.

    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).

  3. Main trial (14 patients): Pulse

    Time frame: Until 12 hours ±30 minutes.

    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).

  4. Main trial (14 patients): Frequency of respiration

    Time frame: Until 12 hours ±30 minutes.

    Frequency of respiration in breaths 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).

  5. Main trial (14 patients): Peripheral saturation

    Time frame: Until 12 hours ±30 minutes.

    Peripheral saturation of oxygen in percent 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).

  6. Main trial (14 patients): Temperature

    Time frame: Until 12 hours ±30 minutes.

    Temperature in degrees Celsius 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).

  7. Main trial (14 patients): Length of stay.

    Time frame: Until 30 days postoperatively.

    Length of stay in hours postoperatively (minimum length of stay: 12 hours but information on length of stay is collected until 30 days postoperatively).

  8. Main trial (14 patients): Length of stay.

    Time frame: Until 30 days postoperatively.

    Length of stay in hours postoperatively (minimum 12 hours).

  9. Main trial (14 patients): Side effects

    Time frame: 10 days postoperatively ±1 day.

    Side effects are evaluated through an objective examination and questions about changes 12 hours ±30 minutes and 10 days postoperatively ±1 day.

  10. Main trial (14 patients): Adverse events

    Time frame: Until 30 days postoperatively.

    Adverse events are registered from the surgery until 30 days postoperatively through medical records and contact with the participant by telephone.

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

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

    The plasma concentrations of metronidazole over time are measured with HPLC-MS until 24 hours after surgery ±4 hours.

  12. Sub-trial (8 patients): Microbiological flora and susceptibility

    Time frame: Until 30 days postoperatively.

    The microbiological flora and susceptibility of specimens collected during the surgery from the abdominal excess fluid and/or swab from the appendices are investigated.

Sponsors and collaborators

Lead sponsor

Herlev Hospital

Other

Collaborators

  • Barbara Juliane Holzknecht (Investigator)
  • Jacob Rosenberg (Sponsor)
  • Johan Juhl Weisser (Partner, data analysis)
  • Magnus Arpi (Investigator)

Registry information

Official study title

The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Feb 8, 2017
Registry last updated
May 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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