Antimicrobial Revision in Patients With Persistent Febrile Neutropenia: A Prospective, Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 主要终点
- Global Success Rate
研究概览
简要总结
Febrile neutropenia is often seen in patients with hematologic malignancies who receive cytotoxic chemotherapy. These patients are usually placed on posaconazole prophylaxis upon starting chemotherapy. If an episode of febrile neutropenia occurs, generally an anti-pseudomonal beta lactam, like cefepime or piperacillin-tazobactam, is initiated. In patients who continue to fever on these agents, the optimal method of antimicrobial revision has yet to be determined.
详细描述
In this prospective, randomized, open-label, single-center trial, the primary objective is to compare the clinical efficacy of two approaches to antimicrobial revision among patients with persistent febrile neutropenia. Neutropenic patients on cefepime or piperacillin-tazobactam who continue to fever for greater than 96 hours will be randomized to receive either meropenem or micafungin dosed according to local guidelines. The primary outcome is a global success rate including a composite of defervescence within 72 hours of meropenem or micafungin initiation, absence of signs or symptoms of infection, and no modification to antimicrobial regimen after initiation of meropenem or micafungin. The secondary outcomes to be collected include in-hospital mortality or discharge to hospice, hospital length of stay, time to defervescence, days of therapy of meropenem or micafungin, rate of Clostridioides difficile infection on meropenem or micafungin, and cause of any proven breakthrough infection while on meropenem or micafungin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 years of age
- •Diagnosis of hematologic malignancy
- •Receiving chemotherapy as treatment of hematologic malignancy
- •Neutropenia defined as an absolute neutrophil count (ANC) ≤ 500 cells/mm3 or an ANC ≤ 1000 cells/mm3 with a predicted decline to < 500 cells/mm3 within 48 hours
- •Prescribed cefepime or piperacillin-tazobactam as initial treatment for febrile neutropenia
- •Persistent fever for ≥ 96 hours since initiation of cefepime or piperacillin-tazobactam OR recurrent fever that occurs ≥ 96 hours since initiation of cefepime or piperacillin-tazobactam (fever defined as single temperature of ≥ 38.3°C (101°F) or a temperature of ≥ 38°C (100.4°F) on two consecutive measures separated by at least one hour)
- •Receipt of posaconazole as neutropenia prophylaxis for at least 3 calendar days
排除标准
- •Clinically or microbiologically confirmed infection at time of enrollment, For example, a positive culture or rapid diagnostic test, positive imaging (X-ray, CT, MRI) or biomarker, such as galactomannan, that is consistent with infection
- •History of infection with organism known to be resistant to meropenem or micafungin
- •Documented allergy to carbapenems or echinocandins
- •Concomitant use of valproic acid
- •Uncontrolled seizure disorder
- •Pregnancy
- •Previous enrollment in this study
研究组 & 干预措施
Meropenem Arm
Patients who meet inclusion criteria may be randomized to meropenem (routine standard of care) dose according to local dosing guidelines to include the use of extended-infusions and adjustments to account for renal function. Duration will be managed by the primary team.
干预措施: Meropenem (Drug)
Micafungin Arm
Patients who meet inclusion criteria may be randomized to micafungin dosed as 150mg intravenously every 24 hours according to local dosing guidelines. Duration will be managed by the primary team.
干预措施: Micafungin (Drug)
结局指标
主要结局
Global Success Rate
时间窗: Hour 72
Percentage of study candidates who meet all of the following criteria: * Defervescence, as defined by a temperature \< 38°C (100.4°F) sustained for at least 24 consecutive hours, within 72 hours of meropenem or micafungin initiation * Absence of signs or symptoms of infection within 72 hours of meropenem or micafungin initiation including but not limited to hypotension, erythema at catheter sites or cellulitis, positive imaging concerning for infection (e.g., pneumonia, osteomyelitis, abscesses etc.), positive cultures or rapid diagnostic tests, positive biomarkers (e.g. galactomannan), dysuria, hypothermia (≤ 35°C or ≤ 95°F) etc. * No modification to antimicrobial regimen after initiation of meropenem or micafungin unless the antibiotic modification is considered de-escalation (e.g. discontinuation of vancomycin)
次要结局
- Hospital length of stay (days)(From hospital admission to discharge, up to 4 days)
- Collection of Causes of any proven breakthrough infection while on meropenem or micafungin(through study completion, an average of 4 days)
- Time to defervescence (hours)(through study completion, an average of 4 days)
- Days of therapy of meropenem or micafungin(through study completion, an average of 4 days)
- Number of Subjects In-hospital mortality or discharge to hospice(From hospital admission to death/discharge to hospice, up to 4 days)
- Rate of Clostridioides difficile infection on meropenem or micafungin(through study completion, an average of 4 days)