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Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis

Primary Purpose

Appendicitis Perforated

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o.
Standard antibiotics intravenously
Sponsored by
Herlev Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Appendicitis Perforated

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥18 years
  • Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual laparoscopic appendectomy
  • Perforated appendicitis (diagnosed during surgery by the surgeon)
  • Negative p-HCG (women)
  • Written informed consent after written and verbal information (preoperatively for the intervention group and postoperatively for the control group)

Exclusion Criteria:

  • Cannot understand, read or speak Danish
  • Previous allergic reaction to fosfomycin, metronidazole, rhGM-CSF, or penicillins e.g. piperacillin or amoxicillin
  • Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy or appendicitis without perforation
  • Other intra-abdominal pathology requiring surgical intervention at the same operation
  • Known renal or hepatic disease or biochemical evidence at the time of admission
  • Known hematologic disease in current medical treatment
  • American Society of Anesthesiologists (ASA) physical status ≥4 (a patient with severe systemic disease that is a constant threat to life)
  • Body weight >110 kg
  • Surgery converted to open appendectomy
  • Anticipated compliance problems

Sites / Locations

  • Department of Surgery, Bispebjerg Hospital
  • Department of Surgery, Herlev Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intervention group

Control group

Arm Description

Outcomes

Primary Outcome Measures

Total length of hospital stay
in hours

Secondary Outcome Measures

Gastrointestinal Quality of Life Index (GIQLI)
A disease-specific questionnaire validated in Danish is collected at 10 days postoperatively (±2 days) and at 30 days postoperatively (±3 days)
Side effects
Number and description. A questionnaire regarding side effects is collected within the first 24 hours after surgery and at 10 days postoperatively (±2 days)
Postoperative complications
Number. According to the Clavien-Dindo grading
Surgical site infections requiring surgical drainage
It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC)
Intraabdominal abscesses requiring drainage
Number. It is defined as an organ/space surgical site infection according to CDC
Readmissions
Number. Only readmissions related to the surgery will be registered; e.g. admission and treatment of a non-related condition will not be registered.
Reoperations
Number. Only reoperations related to the appendectomy will be registered.
Time to return to normal activities
Time period in days. The date is defined at the time point at which the participant could return to normal daily activities.
Period of sick leave "absence from work"
Time periode in days. The parameter is defined as the number of days from the operation to the time point at where the participant returned to work or school.
Costs
The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups.
Adverse events
Microbiological flora and susceptibility
Number and type of positive specimens. If participants have a postoperative infectious complication.

Full Information

First Posted
February 5, 2018
Last Updated
October 14, 2018
Sponsor
Herlev Hospital
Collaborators
Bispebjerg Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03435900
Brief Title
Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis
Official Title
Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Conventional Antibiotics for Perforated Appendicitis - a Pivotal Quasi-randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 14, 2018 (Actual)
Primary Completion Date
July 17, 2018 (Actual)
Study Completion Date
July 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Herlev Hospital
Collaborators
Bispebjerg Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this trial is to evaluate if intraoperative intraperitoneal administration of fosfomycin, metronidazole and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) followed by oral antibiotic for three days is as effective as the current intravenous antibiotic treatment given during and three days after appendectomy for perforated appendicitis. The primary outcome is the total length of hospital stay, defined as the number of hours in hospital after end of operation and until 30-day follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Appendicitis Perforated

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Quasi-randomised controlled trial
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Title
Control group
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o.
Intervention Description
All drugs will be administered together intraperitoneally at the end of the surgery after the appendix has been removed. Hereafter, the intervention group will receive three days of orally administered antibiotics: 500 mg amoxicillin combined with 125 mg clavulanic acid and 500 mg metronidazole. These doses will be administered three times daily.
Intervention Type
Drug
Intervention Name(s)
Standard antibiotics intravenously
Intervention Description
4 g piperacillin/500 mg tazobactam and 1 g metronidazole administered intravenously during surgery followed by 4 g piperacillin/500 mg tazobactam and 500 mg metronidazole administered intravenously three times daily for three days.
Primary Outcome Measure Information:
Title
Total length of hospital stay
Description
in hours
Time Frame
From end of surgery until 30-days follow-up
Secondary Outcome Measure Information:
Title
Gastrointestinal Quality of Life Index (GIQLI)
Description
A disease-specific questionnaire validated in Danish is collected at 10 days postoperatively (±2 days) and at 30 days postoperatively (±3 days)
Time Frame
10 days (±2 days) and 30 days (±3 days) postoperatively
Title
Side effects
Description
Number and description. A questionnaire regarding side effects is collected within the first 24 hours after surgery and at 10 days postoperatively (±2 days)
Time Frame
Within 24 hours after surgery and 10 days (±2 days) postoperatively
Title
Postoperative complications
Description
Number. According to the Clavien-Dindo grading
Time Frame
From end of surgery until 30-days follow-up
Title
Surgical site infections requiring surgical drainage
Description
It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC)
Time Frame
From end of surgery until 30-days follow-up
Title
Intraabdominal abscesses requiring drainage
Description
Number. It is defined as an organ/space surgical site infection according to CDC
Time Frame
From end of surgery until 30-days follow-up
Title
Readmissions
Description
Number. Only readmissions related to the surgery will be registered; e.g. admission and treatment of a non-related condition will not be registered.
Time Frame
From end of surgery until 30-days follow-up
Title
Reoperations
Description
Number. Only reoperations related to the appendectomy will be registered.
Time Frame
From end of surgery until 30-days follow-up
Title
Time to return to normal activities
Description
Time period in days. The date is defined at the time point at which the participant could return to normal daily activities.
Time Frame
From end of surgery until 30-days follow-up
Title
Period of sick leave "absence from work"
Description
Time periode in days. The parameter is defined as the number of days from the operation to the time point at where the participant returned to work or school.
Time Frame
From end of surgery until 30-days follow-up
Title
Costs
Description
The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups.
Time Frame
From end of surgery until 30-days follow-up
Title
Adverse events
Time Frame
From end of surgery until 30-days follow-up
Title
Microbiological flora and susceptibility
Description
Number and type of positive specimens. If participants have a postoperative infectious complication.
Time Frame
From end of surgery until 30-days follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual laparoscopic appendectomy Perforated appendicitis (diagnosed during surgery by the surgeon) Negative p-HCG (women) Written informed consent after written and verbal information (preoperatively for the intervention group and postoperatively for the control group) Exclusion Criteria: Cannot understand, read or speak Danish Previous allergic reaction to fosfomycin, metronidazole, rhGM-CSF, or penicillins e.g. piperacillin or amoxicillin Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy or appendicitis without perforation Other intra-abdominal pathology requiring surgical intervention at the same operation Known renal or hepatic disease or biochemical evidence at the time of admission Known hematologic disease in current medical treatment American Society of Anesthesiologists (ASA) physical status ≥4 (a patient with severe systemic disease that is a constant threat to life) Body weight >110 kg Surgery converted to open appendectomy Anticipated compliance problems
Facility Information:
Facility Name
Department of Surgery, Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Department of Surgery, Herlev Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32432123
Citation
Fonnes S, Roepstorff S, Holzknecht BJ, Olesen CS, Olsen JHH, Schmidt L, Alder R, Gamborg S, Rasmussen T, Arpi M, Jorgensen LN, Rosenberg J. Shorter Total Length of Stay After Intraperitoneal Fosfomycin, Metronidazole, and Molgramostim for Complicated Appendicitis: A Pivotal Quasi-Randomized Controlled Trial. Front Surg. 2020 May 5;7:25. doi: 10.3389/fsurg.2020.00025. eCollection 2020.
Results Reference
derived

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Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis

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