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

NCT07063095 | Recruiting Phase 3

• 1 other identifier: CAVIFOS CCER 2024-01954
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to :

• 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

Keywords

ceftazidime; cavifos; gram-negative bacteria; intravenous fosfomycin

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  From day 1 to day 3 (+/-1 day) of intervention and up to 48h after the last administration of the study medication/placebo

Study Arms (2)

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.

Drug: Ceftazidime± avibactam with fosfomycin

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

PLACEBO COMPARATOR

Control arm will be CAZ±AVI combined with placebo.

Drug: Ceftazidime± avibactam with placebo

Interventions

Ceftazidime± avibactam with fosfomycin 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.

Also known as: CAZ±AVI + FOS, InfectoFos®

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

Ceftazidime± avibactam with placebo 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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnancy or lactation
• Known contra-indication to CAZ±AVI or FOS

Sponsors & Collaborators

• Angela HUTTNER: lead
• Joint Programming Initiative on Antimicrobial Resistance (JPIAMR): collaborator
• Swiss National Science Foundation: collaborator

Study Sites (1)

Hôpitaux Universitaires de Genève

Geneva, Canton of Geneva, 1205, Switzerland

RECRUITING

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

avibactam, ceftazidime drug combination; Fosfomycin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Central Study Contacts

Laura C Lourenço, MD

CONTACT

+41795538659; laura.lourencocordes@hug.ch

Angela Huttner, MD

CONTACT

+41 79 55 33396; angela.huttner@hug.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Attending physician, Division of Infectious Diseases

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: July 14, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)