AppendicitisPhase 2NCT03046758
The Safety and Pharmacokinetics of Intraperitoneal Administration in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
A Phase 2 study testing A combination of fosfomycin, metronidazole and GM-CSF i.p. in people with Appendicitis, run by Herlev Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Appendicitis
- What is being tested?
- A combination of fosfomycin, metronidazole and GM-CSF i.p.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteDenmark
- Study dates
- 24 Feb 2017to 7 Dec 2017
- 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 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men ≥18 years old
- Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual appendectomy
- Written informed consent after written and verbal information
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
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.
- Conditions
- Appendicitis
- Being tested
- A combination of fosfomycin, metronidazole and GM-CSF i.p.
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A combination of fosfomycin, metronidazole and GM-CSF i.p.Drug
All drugs will be administered together intraperitoneally at the end of the surgery after the appendix has been removed.
| Study group | Role | What they receive |
|---|---|---|
| Participants | Experimental | Not described Receives: Drug: A combination of fosfomycin, metronidazole and GM-CSF i.p. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main trial (14 patients): Drop of white blood cell counts
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.
Measured: 4 hours (± 30 minutes)
Sub-trial (8 patients): The pharmacokinetics of fosfomycin.
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.
Measured: Until 24 hours after surgery ±4 hours.
Secondary outcomes (12)
Main trial (14 patients): Biochemical markers
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.
Measured: 4 hours ±30 minutes postoperatively.
Main trial (14 patients): Blood pressure
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).
Measured: Until 12 hours ±30 minutes.
Main trial (14 patients): Pulse
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).
Measured: Until 12 hours ±30 minutes.
Main trial (14 patients): Frequency of respiration
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).
Measured: Until 12 hours ±30 minutes.
Main trial (14 patients): Peripheral saturation
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).
Measured: Until 12 hours ±30 minutes.
Main trial (14 patients): Temperature
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).
Measured: Until 12 hours ±30 minutes.
Main trial (14 patients): Length of stay.
Length of stay in hours postoperatively (minimum length of stay: 12 hours but information on length of stay is collected until 30 days postoperatively).
Measured: Until 30 days postoperatively.
Main trial (14 patients): Length of stay.
Length of stay in hours postoperatively (minimum 12 hours).
Measured: Until 30 days postoperatively.
Main trial (14 patients): Side effects
Side effects are evaluated through an objective examination and questions about changes 12 hours ±30 minutes and 10 days postoperatively ±1 day.
Measured: 10 days postoperatively ±1 day.
Main trial (14 patients): Adverse events
Adverse events are registered from the surgery until 30 days postoperatively through medical records and contact with the participant by telephone.
Measured: Until 30 days postoperatively.
Sub-trial (8 patients): The pharmacokinetics of metronidazole.
The plasma concentrations of metronidazole over time are measured with HPLC-MS until 24 hours after surgery ±4 hours.
Measured: Until 24 hours after surgery ±4 hours.
Sub-trial (8 patients): Microbiological flora and susceptibility
The microbiological flora and susceptibility of specimens collected during the surgery from the abdominal excess fluid and/or swab from the appendices are investigated.
Measured: Until 30 days postoperatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2017 (estimated)
- Study start24 Feb 2017
- Primary completion7 Dec 2017
- Study completion7 Dec 2017
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 AppendicitisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Jacob Rosenberg (Sponsor), Barbara Juliane Holzknecht (Investigator), Magnus Arpi (Investigator), Johan Juhl Weisser (Partner, data analysis)
- Responsible party
- Principal investigator, Siv Fonnes, Herlev Hospital
- Investigators
- Siv Fonnes, MD, Principal investigator, Center for Perioperative Optimization, Department of Surgery, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03046758
- Sponsor's protocol ID
- HEH-SF-01
- Status last verified
- May 2019
- First submitted
- 2 Feb 2017
- Last updated
- 29 May 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 31040341
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
- ClinicalTrials.gov ID
- NCT03046758
- Acronym / sponsor ID
- HEH-SF-01
- Conditions
- Appendicitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Jacob Rosenberg (Sponsor), Barbara Juliane Holzknecht (Investigator), Magnus Arpi (Investigator), Johan Juhl Weisser (Partner, data analysis)
- Study start
- 24 Feb 2017 (actual)
- Primary completion
- 7 Dec 2017 (actual)
- Study completion
- 7 Dec 2017 (actual)
- First posted
- 8 Feb 2017 (estimated)
- 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants | Experimental | Drug: A combination of fosfomycin, metronidazole and GM-CSF i.p. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Men ≥18 years old
- Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual appendectomy
- Written informed consent after written and verbal information
Key exclusion criteria (14 listed)
- 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)
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 |
|---|---|---|
| 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. | Drug | Participants |
Primary outcome
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.
12 secondary outcomes
Main trial (14 patients): Biochemical markers
Time frame: 4 hours ±30 minutes postoperatively.
Main trial (14 patients): Blood pressure
Time frame: Until 12 hours ±30 minutes.
Main trial (14 patients): Pulse
Time frame: Until 12 hours ±30 minutes.
Main trial (14 patients): Frequency of respiration
Time frame: Until 12 hours ±30 minutes.
Main trial (14 patients): Peripheral saturation
Time frame: Until 12 hours ±30 minutes.
Main trial (14 patients): Temperature
Time frame: Until 12 hours ±30 minutes.
Main trial (14 patients): Length of stay.
Time frame: Until 30 days postoperatively.
Main trial (14 patients): Length of stay.
Time frame: Until 30 days postoperatively.
Main trial (14 patients): Side effects
Time frame: 10 days postoperatively ±1 day.
Main trial (14 patients): Adverse events
Time frame: Until 30 days postoperatively.
Sub-trial (8 patients): The pharmacokinetics of metronidazole.
Time frame: Until 24 hours after surgery ±4 hours.
Sub-trial (8 patients): Microbiological flora and susceptibility
Time frame: Until 30 days postoperatively.
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 29 May 2019.
- Results publication: PubMed 31040341Fonnes 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.
- Link to the article regarding the safety (open access)Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Appendicitis
RecruitingObservational study
Prospective Comparison of Pro-Adrenomedullin, C-Reactive Protein, and Neutrophil-to-Lymphocyte Ratio for Diagnosing Acute Appendicitis
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PAINED: Project Addressing INequities in the Emergency Department
Pain, Appendicitis
Not yet recruiting
Comparative Study Between Laparoscopic and Open Appendectomy of Complicated Appendicitis
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Feasibility and Safety of a Pediatric ERAS Protocol for Laparoscopic Appendectomy
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Laparoscopic Antibiotic Lavage to Prevent Intra-abdominal Abscess Formation in Complicated Appendicitis
Complicated Appendicitis, Intra-Abdominal Abscess
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.
Siv Fonnes, MD principal investigator
Center for Perioperative Optimization, Department of Surgery, Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing A combination of fosfomycin, metronidazole and GM-CSF i.p. in people with Appendicitis, run by Herlev Hospital at 1 site 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 3 inclusion and 14 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 29 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Main trial (14 patients): Drop of white blood cell counts (time frame: 4 hours (± 30 minutes)). The study lists 2 primary outcomes in all. 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 NCT03046758, 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 29 May 2019.