BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 174
- 试验地点
- 10
- 主要终点
- Recruitment rate (co-primary outcomes of BALANCE+ vanguard phase)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PLATFORM INCLUSION CRITERIA
- •admitted to a participating hospital
- •positive blood culture with Gram negative (GN) bacterium
排除标准
- •patient's goals of care are for palliation with no active treatment
- •moribund patient, not expected to survive > 72 hours
- •DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA
- •(A) DE-ESCALATION VS. NO DE-ESCALATION DOMAIN
- •Inclusion Criteria
- •1. included in BALANCE+ platform
- •Exclusion Criteria
- •receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive
- •carbapenem-resistance (so that patients will not need to remain on reserve-use agents)
- •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
- •patients with a suspected or proven polymicrobial source of infection
- •(B) BETA-LACTAM VS. NON-BETA-LACTAM ORAL/ENTERAL TREATMENT DOMAIN
- •Inclusion Criteria
- •included in BALANCE+ platform
- •initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment
- •Exclusion Criteria
- •enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy
- •- no-de-escalation arm
- •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
- •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
- •Inclusion Criteria
- •included in BALANCE+ platform
- •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)
- •Exclusion Criteria
- •patient has no ongoing need for a central vascular catheter
- •patient has definite indication for central vascular catheter removal
- •ongoing septic shock with definite/probable line source
- •concomitant S. aureus bacteremia
- •concomitant candidemia
- •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)
- •definite alternative source of GN BSI
- •(D) LOW-RISK AmpC DOMAIN
- •Inclusion Criteria
- •included in BALANCE+ platform
- •positive blood culture with GN bacterium, of the following species
- •Serratia spp.
- •Morganella spp.
- •Providencia spp.
- •Proteus spp. other than P.mirabilis
- •organism is sensitive to ceftriaxone
- •Exclusion Criteria
- •severe allergy to beta-lactams (eg, type 4 hypersensitivity reaction or DRESS)
- •baseline phenotypic resistance to ceftriaxone
- •(E) FOLLOW UP BLOOD CULTURE DOMAIN
- •Inclusion Criteria
- •1. included in BALANCE+ platform
- 另有 6 项未显示
研究组 & 干预措施
De-escalation VS No De-escalation
干预措施: De-escalation VS No De-escalation (Other)
Oral beta-lactams VS Oral Non-beta-lactams
干预措施: Oral beta-lactams VS non beta-lactams (Other)
Central vascular catheter retention VS Central vascular catheter replacement
干预措施: Central vascular catheter retention VS Central vascular catheter replacement (Other)
Cephalosporin VS Carbapenem for low risk AmpC organisms
干预措施: Cephalosporin VS Carbapenem for low risk AmpC organisms (Other)
Routine follow-up blood culture VS No routine follow-up blood culture
干预措施: Routine follow-up blood culture VS No routine follow-up blood culture (Other)
结局指标
主要结局
Recruitment rate (co-primary outcomes of BALANCE+ vanguard phase)
时间窗: 1 year
Recruitment rate will be measured as the number of patients randomized to each study domain, overall, and by individual participating site. Investigators will target a minimum overall recruitment rate of 1 patient/site/month in the de-escalation domain, beta-lactam versus non-beta-lactam stepdown domain, and FUBC domain; and 0.25 patients/site/month in the line replacement domain.
De-escalation versus no de-escalation domain
时间窗: 90 days
* Patient-centered, ordinal Desirability of Outcome Ranking (DOOR) outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new antimicrobial resistance (AMR) colonization or infection from routine cultures
Oral beta-lactam versus non beta-lactam domain
时间窗: 90 days
* Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new AMR colonization or infection from routine cultures
Central vascular catheter retention versus replacement domain
时间窗: 90 days
* Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * No tie-breaker
Low-risk AmpC domain
时间窗: 90 days
* Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * Tie-breaker within ordinal levels: new AMR colonization or infection from routine cultures
Protocol adherence (co-primary outcomes of BALANCE+ vanguard phase)
时间窗: 1 year
Protocol adherence will be calculated differently depending on the domain, but in each case will require adherence to the specific intervention arm and complete follow-up for the primary outcome. Investigators will target ≥90% adherence in each arm of each domain.
Follow-up blood culture domain
时间窗: 90 days
* Ordinal DOOR outcome: (dead at 90 days) \< (alive at 90 days with reinfection and readmission) \< (alive at 90 days with reinfection or readmission) \< (alive at 90 days with neither reinfection nor readmission) * No tie-breaker
次要结局
- 90-day mortality(90 days)
- 90-day all cause readmission(90 days)
- 90-day AMR colonization/infection(90 days)
- 90-day reinfection(90 days)
- 90-day Clostridioides difficile infection (CDI)(90 days)
- 30-day mortality(30 days)
- 60-day mortality(60 days)