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

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ClinicalTrials.gov Identifier: NCT03046758
Recruitment Status : Completed
First Posted : February 8, 2017
Last Update Posted : May 29, 2019
Sponsor:
Collaborators:
Jacob Rosenberg (Sponsor)
Barbara Juliane Holzknecht (Investigator)
Magnus Arpi (Investigator)
Johan Juhl Weisser (Partner, data analysis)
Information provided by (Responsible Party):
Siv Fonnes, Herlev Hospital

Tracking Information
First Submitted Date  ICMJE February 2, 2017
First Posted Date  ICMJE February 8, 2017
Last Update Posted Date May 29, 2019
Actual Study Start Date  ICMJE February 24, 2017
Actual Primary Completion Date December 7, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2017)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03046758 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2017)
  • 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.
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • Main trial (14 patients): Length of stay. [ Time Frame: Until 30 days postoperatively. ]
    Length of stay in hours postoperatively (minimum 12 hours).
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Safety and Pharmacokinetics of Intraperitoneal Administration in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
Official Title  ICMJE The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Appendicitis
Intervention  ICMJE Drug: A combination of fosfomycin, metronidazole and GM-CSF i.p.
All drugs will be administered together intraperitoneally at the end of the surgery after the appendix has been removed.
Study Arms  ICMJE Experimental: Participants
Intervention: Drug: A combination of fosfomycin, metronidazole and GM-CSF i.p.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 4, 2017)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 7, 2017
Actual Primary Completion Date December 7, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03046758
Other Study ID Numbers  ICMJE HEH-SF-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Siv Fonnes, Herlev Hospital
Study Sponsor  ICMJE Herlev Hospital
Collaborators  ICMJE
  • Jacob Rosenberg (Sponsor)
  • Barbara Juliane Holzknecht (Investigator)
  • Magnus Arpi (Investigator)
  • Johan Juhl Weisser (Partner, data analysis)
Investigators  ICMJE
Principal Investigator: Siv Fonnes, MD Center for Perioperative Optimization, Department of Surgery, Herlev Hospital
PRS Account Herlev Hospital
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP