Immediate vs. Deferred Empirical Antifungal Treatment With Voriconazole In High-Risk Neutropenic Patients With Fever And A Positive Panfungal Polymerase Chain Reaction Assay (IDEA Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
研究概览
简要总结
A well-known side-effect of cytostatics (drugs against malignancies) is a decrease in the number of white blood cells, especially of the so-called neutrophil granulocytes, which are very important for the defense against infections. Hence their decrease (called "neutropenia") leads to a predisposition to infections.
Since infections during neutropenia can be very dangerous, the patients are treated with antibiotics from the very first signs of such an infection (usually fever). If the antibiotics (drugs against bacteria) do not lead to a normalization of the body temperature within four days, a drug against fungi is added.
In the IDEA study, one half of the patients receive the antifungal drug voriconazole (as usual) only in case the antibiotics alone do not lead to a normalization of the body temperature (current standard of care). The other half of the patients receive voriconazole immediately after onset of fever (concomitantly with the antibiotics).
The research question is, whether in the "early-treatment" group fewer manifest fungal infections will be observed than in the "late-treatment" group.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Acute leukemia, aggressive lymphoma, bone marrow or stem cell transplantation;
- •Neutropenia (<500 neutrophils/µL) of at least 10 days;
- •Newly diagnosed fever;
- •Positive panfungal polymerase chain reaction assay
排除标准
- •Documented bacterial infection during screening or at randomization
- •Fungemia or other documented invasive fungal infection during screening or at randomization.
研究组 & 干预措施
Early treatment
Voriconazole starts within 18 hours of onset of fever intravenously with a loading dose of 6 mg/kg q12h for the first two doses followed by 4 mg/kg q12h (maintenance dose). Switched to oral treatment (200 mg BID) is possible after at least four days. Treatment will be ended if the patient is afebrile (< 38.0 °C) for 7 days with neutrophil counts < 500/µL, or if the patient is afebrile (< 38.0 °C) for 2 days with neutrophil counts > 500/µL.
干预措施: voriconazole (Vfend) (Drug)
Deferred treatment
Treatment with voriconazole (for dosage see "early treatment arm") is initiated only if a patient is persistently febrile on day 5 after the onset of fever despite antibiotic treatment.
干预措施: voriconazole (Vfend) (Drug)
结局指标
主要结局
Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
时间窗: Day 2 through Day 28
Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion \[fever, body temperature \<36 or \>38 degrees Celsius, graft-versus-host disease, use of corticosteroids\]; and 1 microbiological criterion \[fungal or yeasts\]; or clinical criteria \[abnormal site consistent with infection\]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria. Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit.
次要结局
- Number of Participants Per Reason for Lack of Defervescence(Day 2 through Day 28)
- Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment)(Day 5 (96 hours through 120 hours after start of study treatment))
- Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment)(Day 9 (192 hours through 216 hours after start of study treatment))
- Time to Continuous Defervescence(Day 2 through Day 28)
- Number of Participants That Died on or Before Day 28 (Mortality)(Day 2 through Day 28)
- Time to Negative Panfungal Polymerase Chain Reaction (PCR)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With C-reactive Protein Level >1.25 Times the Upper Limit of Normal (x ULN)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment)(Day 5 (96 hours through 120 hours after start of study treatment))
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment)(Day 2 through Day 9 (192 hours through 216 hours after start of study treatment))
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment)(Day 2 through Day 9 (192 hours through 216 hours after start of study treatment))
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)(Day 2 through Day 28)
- Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)(Day 2 through Day 28)
- Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned(Day 28)
- Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned(Day 28)