NCT03435900

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2018

Shorter than P25 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 5, 2018

Completed
9 days until next milestone

Study Start

First participant enrolled

February 14, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 19, 2018

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 17, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 17, 2018

Completed
Last Updated

October 16, 2018

Status Verified

October 1, 2018

Enrollment Period

5 months

First QC Date

February 5, 2018

Last Update Submit

October 14, 2018

Conditions

Outcome Measures

Primary Outcomes (1)

  • Total length of hospital stay

    in hours

    From end of surgery until 30-days follow-up

Secondary Outcomes (12)

  • Gastrointestinal Quality of Life Index (GIQLI)

    10 days (±2 days) and 30 days (±3 days) postoperatively

  • Side effects

    Within 24 hours after surgery and 10 days (±2 days) postoperatively

  • Postoperative complications

    From end of surgery until 30-days follow-up

  • Surgical site infections requiring surgical drainage

    From end of surgery until 30-days follow-up

  • Intraabdominal abscesses requiring drainage

    From end of surgery until 30-days follow-up

  • +7 more secondary outcomes

Study Arms (2)

Intervention group

EXPERIMENTAL
Drug: Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o.

Control group

ACTIVE COMPARATOR
Drug: Standard antibiotics intravenously

Interventions

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 group

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.

Control group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Department of Surgery, Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Department of Surgery, Herlev Hospital

Herlev, 2730, Denmark

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Appendicitis

Interventions

Metronidazoleregramostim

Condition Hierarchy (Ancestors)

Intraabdominal InfectionsInfectionsGastroenteritisGastrointestinal DiseasesDigestive System DiseasesCecal DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

NitroimidazolesNitro CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Quasi-randomised controlled trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD-student

Study Record Dates

First Submitted

February 5, 2018

First Posted

February 19, 2018

Study Start

February 14, 2018

Primary Completion

July 17, 2018

Study Completion

July 17, 2018

Last Updated

October 16, 2018

Record last verified: 2018-10

Locations