BALANCE+ Vanguard Phase

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-26

Study Completion Date

2024-08-10

Brief Summary

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The goal of the BALANCE+ clinical trial is to transform random care to randomized care for patients with Gram negative bloodstream infections to inform best treatment approaches and optimize outcomes.

BALANCE+, a perpetual platform trial, will efficiently answer multiple questions that are important for hospitalized patients with Gram negative bloodstream infections.

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Detailed Description

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Bloodstream infections (BSIs) are common and lethal, ranking among the top 7 causes of death, with 600,000 cases and 90,000 deaths per year in North America, and 1.2 Million cases and 150,000 deaths per year in Europe. Despite being a leading cause of death worldwide, bloodstream infections remain understudied. Treatment approaches are complicated by rising rates of antimicrobial resistance and declining new drug development.

BALANCE+ provides a platform upon which to answer multiple pressing cross-cutting questions for patients with Gram negative bloodstream infections, including the concept of de-escalating antibiotic spectrum, optimal transition to oral antibiotics, and the role for routine follow up blood culture testing. The trial will also include a syndrome-specific question of whether to remove or retain a central vascular catheter, and a pathogen-specific question of whether cephalosporins are sufficient for patients with low-risk AmpC organisms. As each question is answered, optimal therapies will be adopted into usual care, and new questions will be introduced into the platform of the trial. The evidence generated by BALANCE+ will improve cure for this vulnerable patient population.

Conditions

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Gram-negative Bacteremia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

72 in the overall platform AND at least 12 in each domain.

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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De-escalation VS No De-escalation

Group Type ACTIVE_COMPARATOR

De-escalation VS No De-escalation

Intervention Type OTHER

No de-escalation group: continue to receive the same antibiotic that was started initially (as long as it is confirmed to be effective based on the blood culture sensitivity result)

De-escalation group: switched to narrower spectrum antibiotic.

Oral beta-lactams VS Oral Non-beta-lactams

Group Type ACTIVE_COMPARATOR

Oral beta-lactams VS non beta-lactams

Intervention Type OTHER

Beta-lactam antibiotic: This can be ciprofloxacin, moxifloxacin, levofloxacin or trimethoprim-sulfamethoxazole.

Non beta-lactam antibiotic: This can be, but not limited to, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, or cefixime.

Central vascular catheter retention VS Central vascular catheter replacement

Group Type ACTIVE_COMPARATOR

Central vascular catheter retention VS Central vascular catheter replacement

Intervention Type OTHER

Central vascular catheter replacement: the catheter will be changed by the treating team as soon as possible and within a maximum of 72 hours from blood culture finalization

Central vascular catheter retention: the catheter will not be changed and will be retained until it is no longer needed.

Cephalosporin VS Carbapenem for low risk AmpC organisms

Group Type ACTIVE_COMPARATOR

Cephalosporin VS Carbapenem for low risk AmpC organisms

Intervention Type OTHER

Cephalosporin (ceftriaxone) at standard doses

Carbapenem (like Meropenem, Ertapenem etc) at standard doses

Routine follow-up blood culture VS No routine follow-up blood culture

Group Type ACTIVE_COMPARATOR

Routine follow-up blood culture VS No routine follow-up blood culture

Intervention Type OTHER

Routine follow-up blood culture: routine repeat blood collection 4 days from the index blood collection with positive bacteria.

No follow-up blood culture: no routine repeat blood collection 4 days from the index blood collection with positive bacteria

Interventions

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De-escalation VS No De-escalation

No de-escalation group: continue to receive the same antibiotic that was started initially (as long as it is confirmed to be effective based on the blood culture sensitivity result)

De-escalation group: switched to narrower spectrum antibiotic.

Intervention Type OTHER

Oral beta-lactams VS non beta-lactams

Beta-lactam antibiotic: This can be ciprofloxacin, moxifloxacin, levofloxacin or trimethoprim-sulfamethoxazole.

Non beta-lactam antibiotic: This can be, but not limited to, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, or cefixime.

Intervention Type OTHER

Central vascular catheter retention VS Central vascular catheter replacement

Central vascular catheter replacement: the catheter will be changed by the treating team as soon as possible and within a maximum of 72 hours from blood culture finalization

Central vascular catheter retention: the catheter will not be changed and will be retained until it is no longer needed.

Intervention Type OTHER

Cephalosporin VS Carbapenem for low risk AmpC organisms

Cephalosporin (ceftriaxone) at standard doses

Carbapenem (like Meropenem, Ertapenem etc) at standard doses

Intervention Type OTHER

Routine follow-up blood culture VS No routine follow-up blood culture

Routine follow-up blood culture: routine repeat blood collection 4 days from the index blood collection with positive bacteria.

No follow-up blood culture: no routine repeat blood collection 4 days from the index blood collection with positive bacteria

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. admitted to a participating hospital
2. positive blood culture with Gram negative (GN) bacterium

1\. included in BALANCE+ platform

1. included in BALANCE+ platform
2. initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment

1. included in BALANCE+ platform
2. has an indwelling central vascular catheter that was already in place within the 48-hour period before the onset of bloodstream infection (i.e. is not a new catheter placed within 48 hours of the onset of infection)

1. included in BALANCE+ platform
2. positive blood culture with GN bacterium, of the following species

1. Serratia spp.
2. Morganella spp.
3. Providencia spp.
4. Proteus spp. other than P.mirabilis
5. organism is sensitive to ceftriaxone

1\. included in BALANCE+ platform

Exclusion Criteria

1. patient's goals of care are for palliation with no active treatment
2. moribund patient, not expected to survive \> 72 hours

(A) DE-ESCALATION VS. NO DE-ESCALATION DOMAIN

1. receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive
2. carbapenem-resistance (so that patients will not need to remain on reserve-use agents)
3. no de-escalation option due to any or all of

i. resistance ii. allergies iii. medical contraindications iv. drug-interaction risk v. other relevant reason
4. patients with a suspected or proven polymicrobial source of infection

(B) BETA-LACTAM VS. NON-BETA-LACTAM ORAL/ENTERAL TREATMENT DOMAIN

1. enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy

\- no-de-escalation arm
2. no non-beta-lactam options due to any or all of

i. resistance ii. allergies iii. medical contraindications iv. drug-interaction risk v. other relevant reason
3. no beta-lactam options due to any or all of

i. resistance ii. allergies iii. medical contraindications iv. drug-drug interaction risk v. other relevant reason

(C) CENTRAL VASCULAR CATHETER REPLACEMENT DOMAIN

1. patient has no ongoing need for a central vascular catheter
2. patient has definite indication for central vascular catheter removal

1. ongoing septic shock with definite/probable line source
2. concomitant S. aureus bacteremia
3. concomitant candidemia
4. local suppurative signs (severe redness, warmth, pain, swelling or fluctuance/collection) necessitating catheter removal, or other clinical evidence of infected line (e.g. imaging/echocardiographic findings)
5. definite alternative source of GN BSI

(D) LOW-RISK AmpC DOMAIN

1. severe allergy to beta-lactams (eg, type 4 hypersensitivity reaction or DRESS)
2. baseline phenotypic resistance to ceftriaxone

(E) FOLLOW UP BLOOD CULTURE DOMAIN

1. patient already discharged home prior to day 4
2. definite indication for repeat blood culture testing

1. concomitant Staph. aureus bacteremia
2. concomitant Candidemia
3. clinical suspicion for infective endocarditis (e.g., presence of prosthetic valve, implantable cardiac device)

Eligible Sex

ALL

Accepts Healthy Volunteers

No