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

Appendicitis Perforated Clinical Trial

Official title:

Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Conventional Antibiotics for Perforated Appendicitis - a Pivotal Quasi-randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03435900
• Other study ID #: HEH-SF-02
• Status: Completed
• Phase: Phase 2
• Start date: February 14, 2018
• Est. completion date: July 17, 2018

Study information

• Verified date: October 2018
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: July 17, 2018
• Est. primary completion date: July 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Appendicitis
• Appendicitis Perforated

Intervention

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

Locations

Country	Name	City	State
Denmark	Department of Surgery, Bispebjerg Hospital	Copenhagen
Denmark	Department of Surgery, Herlev Hospital	Herlev

Sponsors (2)

Lead Sponsor	Collaborator
Herlev Hospital	Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total length of hospital stay	in hours	From end of surgery until 30-days follow-up
Secondary	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)	10 days (±2 days) and 30 days (±3 days) postoperatively
Secondary	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)	Within 24 hours after surgery and 10 days (±2 days) postoperatively
Secondary	Postoperative complications	Number. According to the Clavien-Dindo grading	From end of surgery until 30-days follow-up
Secondary	Surgical site infections requiring surgical drainage	It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC)	From end of surgery until 30-days follow-up
Secondary	Intraabdominal abscesses requiring drainage	Number. It is defined as an organ/space surgical site infection according to CDC	From end of surgery until 30-days follow-up
Secondary	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.	From end of surgery until 30-days follow-up
Secondary	Reoperations	Number. Only reoperations related to the appendectomy will be registered.	From end of surgery until 30-days follow-up
Secondary	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.	From end of surgery until 30-days follow-up
Secondary	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.	From end of surgery until 30-days follow-up
Secondary	Costs	The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups.	From end of surgery until 30-days follow-up
Secondary	Adverse events		From end of surgery until 30-days follow-up
Secondary	Microbiological flora and susceptibility	Number and type of positive specimens. If participants have a postoperative infectious complication.	From end of surgery until 30-days follow-up