Appendicitis PerforatedPhase 2NCT03435900
Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Antibiotics for Perforated Appendicitis
A Phase 2 study testing Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o. and Standard antibiotics intravenously in people with Appendicitis Perforated, run by Herlev Hospital at 2 sites in Denmark.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Appendicitis Perforated
- What is being tested?
- Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o. and Standard antibiotics intravenously
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesDenmark
- Study dates
- 14 Feb 2018to 17 Jul 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Department of Surgery, Bispebjerg Hospital
Copenhagen, 2400
Department of Surgery, Herlev Hospital
Herlev, 2730
About this study
Official title: Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Conventional Antibiotics for Perforated Appendicitis - a Pivotal Quasi-randomized Controlled Trial
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.
- Conditions
- Appendicitis Perforated
- Being tested
- Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o., Standard antibiotics intravenously
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o.Drug
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 intravenouslyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Not described Receives: Drug: Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o. |
| Control group | Active comparator | Not described Receives: Drug: Standard antibiotics intravenously |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total length of hospital stay
in hours
Measured: From end of surgery until 30-days follow-up
Secondary outcomes (12)
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)
Measured: 10 days (±2 days) and 30 days (±3 days) postoperatively
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)
Measured: Within 24 hours after surgery and 10 days (±2 days) postoperatively
Postoperative complications
Number. According to the Clavien-Dindo grading
Measured: From end of surgery until 30-days follow-up
Surgical site infections requiring surgical drainage
It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC)
Measured: From end of surgery until 30-days follow-up
Intraabdominal abscesses requiring drainage
Number. It is defined as an organ/space surgical site infection according to CDC
Measured: From end of surgery until 30-days follow-up
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.
Measured: From end of surgery until 30-days follow-up
Reoperations
Number. Only reoperations related to the appendectomy will be registered.
Measured: From end of surgery until 30-days follow-up
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.
Measured: From end of surgery until 30-days follow-up
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.
Measured: From end of surgery until 30-days follow-up
Costs
The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups.
Measured: From end of surgery until 30-days follow-up
Adverse events
Measured: From end of surgery until 30-days follow-up
Microbiological flora and susceptibility
Number and type of positive specimens. If participants have a postoperative infectious complication.
Measured: From end of surgery until 30-days follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start14 Feb 2018
- Primary completion17 Jul 2018
- Study completion17 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Appendicitis PerforatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Quasi-randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bispebjerg Hospital
- Responsible party
- Principal investigator, Siv Fonnes, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03435900
- Sponsor's protocol ID
- HEH-SF-02
- Status last verified
- Oct 2018
- First submitted
- 5 Feb 2018
- Last updated
- 16 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 32432123
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraperitoneal Administration of Fosfomycin, Metronidazole and Molgramostim Versus Intravenous Conventional Antibiotics for Perforated Appendicitis - a Pivotal Quasi-randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03435900
- Acronym / sponsor ID
- HEH-SF-02
- Conditions
- Appendicitis Perforated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Bispebjerg Hospital
- Study start
- 14 Feb 2018 (actual)
- Primary completion
- 17 Jul 2018 (actual)
- Study completion
- 17 Jul 2018 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Quasi-randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Intervention group |
| Standard antibiotics intravenously4 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. | Drug | Control group |
Primary outcome
Total length of hospital stay
Time frame: From end of surgery until 30-days follow-up
in hours
12 secondary outcomes
Gastrointestinal Quality of Life Index (GIQLI)
Time frame: 10 days (±2 days) and 30 days (±3 days) postoperatively
Side effects
Time frame: Within 24 hours after surgery and 10 days (±2 days) postoperatively
Postoperative complications
Time frame: From end of surgery until 30-days follow-up
Surgical site infections requiring surgical drainage
Time frame: From end of surgery until 30-days follow-up
Intraabdominal abscesses requiring drainage
Time frame: From end of surgery until 30-days follow-up
Readmissions
Time frame: From end of surgery until 30-days follow-up
Reoperations
Time frame: From end of surgery until 30-days follow-up
Time to return to normal activities
Time frame: From end of surgery until 30-days follow-up
Period of sick leave "absence from work"
Time frame: From end of surgery until 30-days follow-up
Costs
Time frame: From end of surgery until 30-days follow-up
Adverse events
Time frame: From end of surgery until 30-days follow-up
Microbiological flora and susceptibility
Time frame: From end of surgery until 30-days follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Derived from this study: PubMed 32432123Fonnes 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.
- Individual participant dataSharing planned: Undecided
Related trials for Appendicitis Perforated
Not yet recruiting
Comparative Study Between Laparoscopic and Open Appendectomy of Complicated Appendicitis
Appendicitis, Perforated Appendicitis
Not yet recruitingPhase 3
Piperacillin/Tazobactam Versus Ceftriaxone and Metronidazole for Children With Perforated Appendicitis
Appendicitis Perforated, Appendectomy, Laparoscopic
Not yet recruiting
Perforated Appendicitis and Postoperative Antibiotics Pilot Trial
Perforated Appendicitis
Active, not recruiting
Effect of Probiotic's Consumption on Several Markers in Perforated Appendix Patients With Diffuse Peritonitis
Appendicitis With Perforation, Appendectomy
Active, not recruitingPhase 2
Use of Antibiotic Irrigation to Decrease Wound Infections in Pediatric Perforated Appendicitis
Perforated Appendicitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination of fosfomycin, metronidazole and rhGM-CSF (administered together intraperitoneally) and three days of antibiotics p.o. and Standard antibiotics intravenously in people with Appendicitis Perforated, run by Herlev Hospital at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total length of hospital stay (time frame: From end of surgery until 30-days follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03435900, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.