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

Angela HUTTNER

Status and phase: Not yet enrolling; Phase 3

Conditions: Sepsis and Septic Shock; Gram Negative Infections

Treatments: Drug: Ceftazidime± avibactam with fosfomycin; Drug: Ceftazidime± avibactam with placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07063095

CAVIFOS CCER 2024-01954

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Drug: Ceftazidime± avibactam with fosfomycin

Ceftazidime± avibactam with placebo (CAZ±AVI + placebo)

Placebo Comparator group

Description:

Control arm will be CAZ±AVI combined with placebo.

Treatment:

Drug: Ceftazidime± avibactam with placebo