Gram Negative InfectionsPhase 3CAVIFOSNCT07063095
A Combination Therapy With Ceftazidime and Fosfomycin Will be Compared to Ceftazidime Alone in Hospitalized Adult Patients With Suspected Severe Gram-negative Bacterial Infections
A Phase 3 study testing Ceftazidime± avibactam with fosfomycin in people with Gram Negative Infections and Sepsis and Septic Shock, run by Angela HUTTNER at 1 site in Switzerland.
Trial summary
The goal of this clinical trial is to : 1. Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram Negative Infections, Sepsis and Septic Shock
- What is being tested?
- Ceftazidime± avibactam with fosfomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSwitzerland
- Study dates
- 25 Aug 2025to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Adult (≥18 years)
- Hospitalized with suspected severe Gram-negative bacterial infection
- Signed informed consent from the patient (or oral consent from a patient with capacity but with physical inability to sign, with signed witness testimony from a person independent of the study team) of from the legal representative if the patient lacks capacity to provide informed consent
Who cannot join
- Pregnancy or lactation
- Known contra-indication to CAZ±AVI or FOS
- Gram-negative directed antibiotic treatment begun >24 hours before inclusion
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Hôpitaux Universitaires de Genève
Geneva, Canton of Geneva, 1205
Laura Lourenço, MD, +41 7955 38 659, lloo@hug.ch
About this study
Official title: Ceftazidime Plus Fosfomycin Versus Ceftazidime Alone for Severe Gram-negative Infections: a Triple-blind, Placebo-controlled Point-of-care Randomized Clinical Trial
The goal of this clinical trial is to :
- Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone)
- to further characterize the safety profile of this combination therapy
Read more
In the presence of such an infection, standard treatment is to start intravenous antibiotic therapy. Ceftazidime (Fortam®), or ceftazidime-avibactam (Zavicefta®), is a standard antibiotic commonly used for this purpose (for very resistant bacteria, the compound avibactam is included to protect ceftazidime from being broken down by bacteria).
Researchers will compare ceftazidime (or ceftazdime-avibactam) plus fosfomycin versus ceftazidime alone with placebo (i.e. a look-alike substance given with no drug) to examine whether the addition of another intravenous antibiotic, fosfomycin, would lead to faster recovery from severe infection and evaluate the tolerability of this combination.
Participants will:
- Be randomly assigned to either the intervention group or the control group.
- The intervention group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected, per routine practice) and intravenous fosfomycin, and the control group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected) and placebo.
- Either treatment will be given for 3 days, three times daily (or less frequently, depending on renal function).
- Provide a few extra blood samples (for CRP measurement, a protein marker of inflammation) during the first few days of the study.
- Be contacted in the hospital or by phone if discharged on day 28 to be asked a few questions.
- Conditions
- Gram Negative Infections, Sepsis and Septic Shock
- Being tested
- Ceftazidime± avibactam with fosfomycin, Ceftazidime± avibactam with placebo
- Keywords
- ceftazidime, cavifos, gram-negative bacteria, intravenous fosfomycin
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime± avibactam with fosfomycinDrug
Also called CAZ±AVI + FOS, InfectoFos®
The intervention will last 72h (±6h). Ceftazidime will be administered intravenously in 5% glucose serum (per hospital standard), either intermittently (divided into three doses daily) or as continuous infusion; doses will be adapted to renal function. The decision to administer CAZ by continuous infusion and to add AVI will be left to the attending physician. CAZ±AVI will be adjusted for renal insufficiency per internal guidelines of dosing and international recommendations.
The use of CAZ with its paired beta-lactamase inhibitor avibactam, i.e., the use of ceftazidime-avibactam (Zavicefta®) instead of CAZ will occur in case of suspicion of infection by either extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-E), cephalosporinase-carrying Enterobacterales (ampC-E) or carbapenem-resistant Enterobacterales (CRE), as determined by treating physician and/or the infectious diseases consultant.
Ceftazidime± avibactam with placeboDrug
Participants randomized to the control arm will receive placebo infusion. Placebo will be 5% glucose serum and will be administered IV with the same frequency as FOS would be for the participant's renal function.
| Study group | Role | What they receive |
|---|---|---|
| Ceftazidime± avibactam with fosfomycin (CAZ±AVI+ FOS) | Experimental | The experimental intervention is a combination of CAZ with FOS, brand name InfectoFos®, each vial containing 2 g of fosfomycin, and 2.64 g fosfomycin disodium. Receives: Drug: Ceftazidime± avibactam with fosfomycin |
| Ceftazidime± avibactam with placebo (CAZ±AVI + placebo) | Placebo comparator | Control arm will be CAZ±AVI combined with placebo. Receives: Drug: Ceftazidime± avibactam with placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time in hours from first study-medication administration to normalization of all qSOFA parameters and decrease of peak CRP by 50%.
qSOFA scores will be collected as per routine ward practices and at minimum every 2 hours for patients with abnormal scores, until normalization.
CRP will be measured twice daily (12 ± 4 hours apart), for 6 days or until the 50% reduction from peak is observed, whichever occurs earlier. Thereafter, measurements will be taken as clinically indicated.
Measured: From date of randomization until the date of first documented normalization of qSOFA and 50% decrease in CRP. We estimate median time to be of approximately 108h and 96h in the control and intervention groups, respectively (approx 4 to 5 days)
Secondary outcomes (1)
Incidence of adverse events of special interest (AESI)
Patients will be monitored post-randomization for the occurrence of adverse events of special interest (AESI), defined as follows:
- New-onset pulmonary edema detected by imaging or auscultatory exam beginning during and up to 2 days after treatment with study antibiotic(s)
- New-onset hypernatremia beginning during and up to 2 days after treatment with study antibiotic(s)
- New-onset hypokalemia beginning during and up to 2 days after treatment with study antibiotic(s)
- New-onset gastrointestinal events (abdominal pain, nausea, vomiting, and/or diarrhea) beginning during and up to 2 days after treatment with study antibiotic(s)
Measured: From day 1 to day 3 (+/-1 day) of intervention and up to 48h after the last administration of the study medication/placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2025
- Study start25 Aug 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram Negative InfectionsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Angela HUTTNER
- Sponsor type
- University, hospital or other
- Collaborators
- Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Swiss National Science Foundation
- Responsible party
- Sponsor-investigator, Angela HUTTNER, University of Geneva, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07063095
- Sponsor's protocol ID
- CAVIFOS CCER 2024-01954
- Acronym
- CAVIFOS
- Status last verified
- Aug 2025
- First submitted
- 11 Jun 2025
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ceftazidime Plus Fosfomycin Versus Ceftazidime Alone for Severe Gram-negative Infections: a Triple-blind, Placebo-controlled Point-of-care Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07063095
- Acronym / sponsor ID
- CAVIFOS / CAVIFOS CCER 2024-01954
- Conditions
- Gram Negative Infections, Sepsis and Septic Shock
- Keywords
- ceftazidime, cavifos, gram-negative bacteria, intravenous fosfomycin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Angela HUTTNERUniversity, hospital or other
- Collaborators
- Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Swiss National Science Foundation
- Study start
- 25 Aug 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 14 Jul 2025 (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 goal of this clinical trial is to :
- Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone)
- to further characterize the safety profile of this combination therapy
In the presence of such an infection, standard treatment is to start intravenous antibiotic therapy. Ceftazidime (Fortam®), or ceftazidime-avibactam (Zavicefta®), is a standard antibiotic commonly used for this purpose (for very resistant bacteria, the compound avibactam is included to protect ceftazidime from being broken down by bacteria).
Researchers will compare ceftazidime (or ceftazdime-avibactam) plus fosfomycin versus ceftazidime alone with placebo (i.e. a look-alike substance given with no drug) to examine whether the addition of another intravenous antibiotic, fosfomycin, would lead to faster recovery from severe infection and evaluate the tolerability of this combination.
Participants will:
- Be randomly assigned to either the intervention group or the control group.
- The intervention group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected, per routine practice) and intravenous fosfomycin, and the control group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected) and placebo.
- Either treatment will be given for 3 days, three times daily (or less frequently, depending on renal function).
- Provide a few extra blood samples (for CRP measurement, a protein marker of inflammation) during the first few days of the study.
- Be contacted in the hospital or by phone if discharged on day 28 to be asked a few questions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ceftazidime± avibactam with fosfomycin (CAZ±AVI+ FOS) | Experimental | Drug: Ceftazidime± avibactam with fosfomycinThe experimental intervention is a combination of CAZ with FOS, brand name InfectoFos®, each vial containing 2 g of fosfomycin, and 2.64 g fosfomycin disodium. |
| Ceftazidime± avibactam with placebo (CAZ±AVI + placebo) | Placebo comparator | Drug: Ceftazidime± avibactam with placeboControl arm will be CAZ±AVI combined with placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult (≥18 years)
- Hospitalized with suspected severe Gram-negative bacterial infection
- Signed informed consent from the patient (or oral consent from a patient with capacity but with physical inability to sign, with signed witness testimony from a person independent of the study team) of from the legal representative if the patient lacks capacity to provide informed consent
Key exclusion criteria (3 listed)
- Pregnancy or lactation
- Known contra-indication to CAZ±AVI or FOS
- Gram-negative directed antibiotic treatment begun >24 hours before inclusion
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 |
|---|---|---|
| Ceftazidime± avibactam with fosfomycinAlso: CAZ±AVI + FOS, InfectoFos®The intervention will last 72h (±6h). Ceftazidime will be administered intravenously in 5% glucose serum (per hospital standard), either intermittently (divided into three doses daily) or as continuous infusion; doses will be adapted to renal function. The decision to administer CAZ by continuous infusion and to add AVI will be left to the attending physician. CAZ±AVI will be adjusted for renal insufficiency per internal guidelines of dosing and international recommendations. The use of CAZ with its paired beta-lactamase inhibitor avibactam, i.e., the use of ceftazidime-avibactam (Zavicefta®) instead of CAZ will occur in case of suspicion of infection by either extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-E), cephalosporinase-carrying Enterobacterales (ampC-E) or carbapenem-resistant Enterobacterales (CRE), as determined by treating physician and/or the infectious diseases consultant. | Drug | Ceftazidime± avibactam with fosfomycin (CAZ±AVI+ FOS) |
| Ceftazidime± avibactam with placeboParticipants randomized to the control arm will receive placebo infusion. Placebo will be 5% glucose serum and will be administered IV with the same frequency as FOS would be for the participant's renal function. | Drug | Ceftazidime± avibactam with placebo (CAZ±AVI + placebo) |
Primary outcome
Time in hours from first study-medication administration to normalization of all qSOFA parameters and decrease of peak CRP by 50%.
Time frame: From date of randomization until the date of first documented normalization of qSOFA and 50% decrease in CRP. We estimate median time to be of approximately 108h and 96h in the control and intervention groups, respectively (approx 4 to 5 days)
qSOFA scores will be collected as per routine ward practices and at minimum every 2 hours for patients with abnormal scores, until normalization. CRP will be measured twice daily (12 ± 4 hours apart), for 6 days or until the 50% reduction from peak is observed, whichever occurs earlier. Thereafter, measurements will be taken as clinically indicated.
1 secondary outcome
Incidence of adverse events of special interest (AESI)
Time frame: From day 1 to day 3 (+/-1 day) of intervention and up to 48h after the last administration of the study medication/placebo
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Individual participant dataSharing planned: No
Related trials for Gram Negative Infections
Not yet recruitingPhase 4
Evaluation of the Impact of Oral Ivermectin on Musca Sorbens Flies, Putative Vector of Trachoma
Survival of Flies Developing in Faecal Samples
Not yet recruitingPhase 2
Curcumin Extract Added to Ciprofloxacin for Typhoid Carriers Among Food Handlers of the Free Nutritious Meal Program
Typhoid Carrier, Typhoid Fever
RecruitingObservational study
Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders
Trisomy 8 Mosaicism, Trisomy 8 Associated Autoinflammatory Disease
RecruitingPhase 2
Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections
Gram-negative Bacterial Infections
RecruitingPhase 3
Keverprazan-Minocycline Dual Therapy of Different Durations Versus Bismuth Quadruple Therapy for Helicobacter Pylori Eradication.
Helicobacter Infection
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ceftazidime± avibactam with fosfomycin in people with Gram Negative Infections and Sepsis and Septic Shock, run by Angela HUTTNER at 1 site in Switzerland.
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 3 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: looking for participants now, as of the sponsor's last update on 26 Sep 2025. 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 Switzerland. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura C Lourenço, MD (+41795538659, laura.lourencocordes@hug.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time in hours from first study-medication administration to normalization of all qSOFA parameters and decrease of peak CRP by 50%. (time frame: From date of randomization until the date of first documented normalization of qSOFA and 50% decrease in CRP. We estimate median time to be of approximately 108h and 96h in the control and intervention groups, respectively (approx 4 to 5 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Sep 2025.