An Investigator Initiated, Phase II Single-Center, Randomized, Open-Label, Prospective, Study To Determine The Impact Of Serial Procalcitonin On Improving Antimicrobial Stewardship And On The Efficacy, Safety, And Tolerability Of Imipenem-Cilastatin-Relebactam Plus/Minus Vancomycin Or Linezolid Versus Standard Of Care Antipseudomonal Beta-Lactams Plus/Minus Vancomycin Or Linezolid As Empiric Therapy In Febrile Neutropenic Adults With Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Clinical Outcome in the MITT Analysis Set at EOIV.
研究概览
简要总结
This phase II trial studies the effect of imipenem-relebactam in treating patients with cancer who have a fever due to low white blood cell counts (febrile neutropenia). In this study, imipenem-relebactam will be compared to the standard-of-care treatment (cefepime, meropenem, or piperacillin/tazobactam) for the treatment of febrile neutropenia. Imipenem-relebactam is used to treat infections. Giving imipenem-relebactam may help to control febrile neutropenia in patients with cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of imipenem-relebactam plus vancomycin, daptomycin, or linezolid compared with SOC plus vancomycin, daptomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I (TREATMENT): Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or orally (PO) q12h. Patients may continue to receive imipenem/cilastatin/relebactam IV over 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
GROUP II (STANDARD OF CARE): Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
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
- •Has provided written informed consent, and has the willingness and ability to comply with all study procedures
- •>= 18 years old
- •Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation
- •Neutropenic fever is defined as the presence of neutropenia defined by:
- •Absolute neutrophil count (ANC) < 500 cells/mm3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as:
- •Single oral temperature measurement of > 100.4 degree F (38.0 degree C).
- •Requires hospitalization for IV empiric antibiotic therapy
- •If female:
- •Not breastfeeding
- •Agrees to not attempt to become pregnant during the study. Is surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, has negative screening serum or urine pregnancy test within 5 days
- •If of childbearing potential (including being < 2 years postmenopausal), is willing to practice sexual abstinence or use an effective dual form of contraception with her partner (eg, 2 barrier methods, barrier method plus hormonal method) during treatment and up 28 days post treatment
排除标准
- •History of any hypersensitivity or allergic reaction to any carbapenem
- •Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
- •Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
- •Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
- •Evidence of significant hepatic impairment (any of the following):
- •Known acute viral hepatitis
- •Alanine aminotransferase (ALT) level > 5 times the upper limit of normal (x upper limit of normal [ULN]). Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease
- •Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy
- •Known to be human immunodeficiency virus positive
- •Severely impaired renal function, defined as creatinine clearance (CrCl) =< 30 mL/min estimated by the Cockcroft-Gault formula
- •Expected requirement for hemodialysis while on study therapy
- •Received > 36 hours of IV antibacterial therapy (with study drugs) within 72 hours of the initiation of inpatient IV study drug for treatment of suspected infection. Antibiotic prophylaxis and oral antibiotics is allowed. Prophylactic use of antiviral or antifungal medication is permitted
- •Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood
- •Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid replacement)
- •Unable or unwilling to adhere to the study-specified procedures and restrictions
- •Any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study (eg, would place a patient at risk or compromise the quality of the data
- •Participation in any other ongoing imipenem-relebactam trial
研究组 & 干预措施
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Vancomycin (Drug)
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Daptomycin (Drug)
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Linezolid (Drug)
Group I (imipenem, cilastatin, relebactam)
Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes q6h for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h. Patients may continue to receive imipenem/cilastatin/relebactam IVover 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
干预措施: Imipenem/Cilastatin/Relebactam (Drug)
Group I (imipenem, cilastatin, relebactam)
Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes q6h for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h. Patients may continue to receive imipenem/cilastatin/relebactam IVover 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
干预措施: Daptomycin (Drug)
Group I (imipenem, cilastatin, relebactam)
Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes q6h for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h. Patients may continue to receive imipenem/cilastatin/relebactam IVover 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
干预措施: Vancomycin (Drug)
Group I (imipenem, cilastatin, relebactam)
Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes q6h for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h. Patients may continue to receive imipenem/cilastatin/relebactam IVover 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
干预措施: Linezolid (Drug)
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Cefepime (Drug)
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Meropenem (Drug)
Group II (cefepime, meropenem, piperacillin/tazobactam)
Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.
干预措施: Piperacillin-Tazobactam (Drug)
结局指标
主要结局
Clinical Outcome in the MITT Analysis Set at EOIV.
时间窗: Within 72 hours after administration of the last dose of inpatient IV study drug.
The primary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.
次要结局
- Clinical Outcome in the CE Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Clinical Outcome in the MITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- 30-Day All-cause Mortality in the MITT Analysis Set.(30 days after the last dose of inpatient IV study drug.)
- Clinical Outcome in the ME Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Microbiological Outcome in the mMITT Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Microbiological Outcome in the mMITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Clinical Outcome in the mMITT Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Clinical Outcome in the CE Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Clinical Outcome in the MITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Clinical Outcome in the CE Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Clinical Outcome in the ME Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Microbiological Outcome in the mMITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Infection-related Mortality in the MITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Clinical Outcome in the mMITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Clinical Outcome in the mMITT Analysis Set at LFU.(Pateints in mMITT (Microbiological Modified Intent-To-Treat) Analysis Set)
- Clinical Outcome in the ME Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Microbiological Outcome in the ME Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Microbiological Outcome in the ME Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Microbiological Outcome in the ME Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Infection-related Mortality in the mMITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Infection-related Mortality in the MITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- Infection-related Mortality in the mMITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug.)
- 30-Day All-cause Mortality in the mMITT Analysis Set.(30 days after the last dose of inpatient IV study drug.)