Treatment Strategies for Bacterial Blood Infections

Recruiting in Palo Alto (17 mi)

+22 other locations

Overseen by Rob A Fowler, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Palliative care, Moribund, Polymicrobial infection, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

BALANCE+ is a perpetual multiple domain randomized controlled platform trial to evaluate various treatment strategies for Gram-negative bloodstream infections (GN BSIs). Each domain addresses critical questions in the management of GN BSIs, aiming to refine treatment strategies, enhance patient outcomes, and reduce antimicrobial resistance. The initial vanguard pilot RCT (NCT05893147) started on 29 August 2023 and has successfully completed the pilot phase on 24-Apr-2024. All patients enrolled in the vanguard phase are part of the main platform trial.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, there are exclusions related to drug interactions and medical contraindications, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug cefiderocol for bacterial blood infections?

Cefiderocol has shown effectiveness in treating serious Gram-negative bacterial infections, including those resistant to other antibiotics, in clinical trials for conditions like complicated urinary tract infections and pneumonia. It has demonstrated potent activity against multidrug-resistant pathogens, making it a promising option for infections with limited treatment alternatives. ^{1 2 3 4 5}

Is cefiderocol safe for treating bacterial infections?

Cefiderocol has been shown to be generally safe in clinical trials, with common side effects including gastrointestinal symptoms like diarrhea and nausea. However, some studies noted a higher mortality rate in patients treated with cefiderocol compared to other treatments, though the exact cause is unclear. ^{1 2 3 5 6}

What makes the drug cefiderocol unique for treating bacterial blood infections?

Cefiderocol is unique because it is a novel antibiotic that uses a siderophore mechanism to penetrate Gram-negative bacteria, making it effective against multidrug-resistant strains. It is stable against all four classes of beta-lactamases, which are enzymes that many bacteria use to resist antibiotics. ^{1 7 8 9 10}

Research Team

Nick Daneman, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Rob A Fowler, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for patients with Gram-negative bloodstream infections, which can lead to conditions like sepsis. Participants must meet certain health standards not specified here. People who don't fit the study's specific medical criteria cannot join.

Inclusion Criteria

Positive blood culture with Gram negative (GN) bacterium

Positive blood culture with GN bacterium, of the following species: i. Serratia spp. ii Morganella spp. iii Providencia spp. iv Proteus spp. other than P.mirabilis

Included in BALANCE+ platform

Exclusion Criteria

I cannot switch to a milder treatment due to allergies, resistance, or other health risks.

> 24 hours since index blood culture susceptibility results finalization

I am part of another study that restricts oral treatments.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various treatment strategies for Gram-negative bloodstream infections, including antibiotic de-escalation, oral antibiotic choices, and central line management

90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on outcomes such as reinfection, readmission, and antimicrobial resistance

90 days

Open-label extension (optional)

Participants may continue to receive treatment as part of the adaptive platform trial, with adjustments based on interim analyses

Treatment Details

Interventions

• Cephalosporin (Antibiotic)
• De-escalation (Antibiotic)
• Oral beta-lactams (Antibiotic)

Trial Overview The BALANCE+ trial tests different treatments for bacterial blood infections: routine vs no follow-up blood culture, de-escalation of treatment or not, oral beta-lactams vs other drugs, and strategies for managing central vascular catheters.

Participant Groups

Group I: De-escalation VS No De-escalation Active Control 1 Intervention

Group II: Oral beta-lactams VS Oral Non-beta-lactams Active Control 1 Intervention

Group III: Routine follow-up blood culture VS No routine follow-up blood culture Active Control 1 Intervention

Group IV: Central vascular catheter retention VS Central vascular catheter replacement Active Control 1 Intervention

Group V: Cephalosporin VS Carbapenem for low risk AmpC organisms Active Control 1 Intervention

Cephalosporin is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Fetroja for:

• Urinary Tract Infection
• Bacterial Pneumonia

🇪🇺 Approved in European Union as Cefiderocol for:

• Complicated urinary tract infections
• Hospital-acquired pneumonia
• Ventilator-associated pneumonia

🇨🇦 Approved in Canada as Cefiderocol for:

• Complicated urinary tract infections
• Hospital-acquired pneumonia
• Ventilator-associated pneumonia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Eastern Regional Health Authority Saint John's, Canada

Sunnybrook Health Sciences Centre Toronto, Canada

Mount Sinai Hospital Toronto, Canada

University Health Network Toronto, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Patients Recruited

1,569,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1417

Patients Recruited

26,550,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections. Syed, YY.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence. Viale, P., Sandrock, CE., Ramirez, P., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-Resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety. Lee, YR., Yeo, S.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cefiderocol in clinical practice. Maseda, E., Suárez de la Rica, A.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol. Soriano, MC., Montufar, J., Blandino-Ortiz, A.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol. Taheri, Y., Joković, N., Vitorović, J., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians. Principe, L., Lupia, T., Andriani, L., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbapenem-Resistant Enterobacterales Infection After Massive Blast Injury: Use of Cefiderocol Based Combination Therapy. Carney, BW., Rizzo, JA., Alderete, JF., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria. Silva, JT., López-Medrano, F.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acquisition of transferable extrachromosomal fec operon is associated with a cefiderocol MIC increase in Enterobacterales. Kocer, K., Boutin, S., Heeg, K., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-Resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

The role of cefiderocol in clinical practice. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Cefiderocol. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Carbapenem-Resistant Enterobacterales Infection After Massive Blast Injury: Use of Cefiderocol Based Combination Therapy. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria. [2023]

10. England pubmed.ncbi.nlm.nih.gov

The acquisition of transferable extrachromosomal fec operon is associated with a cefiderocol MIC increase in Enterobacterales. [2023]