A Combination Therapy With Ceftazidime and Fosfomycin Will be Compared to Ceftazidime Alone in Hospitalized Adult Patients With Suspected Severe Gram-negative Bacterial Infections

NCT ID: NCT07063095

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-25
• Study Completion Date: 2026-12-31

Brief 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 reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone)

2. 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.

Conditions

Gram Negative Infections; Sepsis and Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ceftazidime± avibactam with fosfomycin (CAZ±AVI+ FOS)

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.

Group Type: EXPERIMENTAL

Ceftazidime± avibactam with fosfomycin

Intervention Type: DRUG

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 placebo (CAZ±AVI + placebo)

Control arm will be CAZ±AVI combined with placebo.

Group Type: PLACEBO_COMPARATOR

Ceftazidime± avibactam with placebo

Intervention Type: DRUG

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.

Interventions

Ceftazidime± avibactam with fosfomycin

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.

Intervention Type: DRUG

Ceftazidime± avibactam with placebo

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.

Intervention Type: DRUG

Other Intervention Names

CAZ±AVI + FOS; InfectoFos®

Eligibility Criteria

Inclusion Criteria

1. Adult (≥18 years)

2. Hospitalized with suspected severe Gram-negative bacterial infection

3. 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

Exclusion Criteria

1. Pregnancy or lactation

2. Known contra-indication to CAZ±AVI or FOS

3. Gram-negative directed antibiotic treatment begun >24 hours before inclusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)

UNKNOWN

Sponsor Role: collaborator

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

Angela HUTTNER

OTHER

Sponsor Role: lead

Responsible Party

Angela HUTTNER

Professor, Attending physician, Division of Infectious Diseases

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Hôpitaux Universitaires de Genève

Geneva, Canton of Geneva, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Laura C Lourenço, MD

Role: CONTACT

laura.lourencocordes@hug.ch

+41795538659

Angela Huttner, MD

Role: CONTACT

angela.huttner@hug.ch

+41 79 55 33396

Facility Contacts

Laura Lourenço, MD

Role: primary

lloo@hug.ch

+41 7955 38 659

Other Identifiers

CAVIFOS CCER 2024-01954

Identifier Type: -

Identifier Source: org_study_id