Stopping Antibiotics After 3 Days for the Treatment of FEbrile Neutropenia in Haematology Patients (SAFE Study): a Randomized Open-label Non-inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 410
- 试验地点
- 1
- 主要终点
- Absence of a serious medical complication (SMC) following 42 days after randomisation. SMC is defined as: Death; and/or ICU admission; and/or Septic shock requiring vasopressive therapy.
研究概览
简要总结
The goal of this clinical trial is to compare a short course of antibiotics in patients in whom no bacterial infection is found with the current "golden standard": long-term antibiotic treatment in adult hematology patients who develop neutropenic fever.
The main question it aims to answer is: whether the short-term treatment is equally safe for patients, hence the name 'SAFE study'.
Participants will be randomly assigned (randomized) to one of two treatment options once they develop neutropenic fever: short-term or long-term antibiotic treatment. An additional blood sample, urine sample and stool sample will be collected.
Researchers will compare the short-term and the long-term antibiotic treatment groups to see if the short treatment is equally safe as the long-term 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
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures;
- •Age older than 16 years;
- •Intensive therapy is started within three days before randomization for one of the following haematological conditions:
- •Remission induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); OR
- •Re-induction chemotherapy for relapsed after haematological remission lasting for a minimum duration of 6 months; OR
- •Conditioning regimen to prepare for an allogeneic HCT; OR
- •Conditioning regimen to prepare for an autologous HCT.
- •Expected longstanding (≥ 7 days) neutropenia (ANC < 0.5x10^9/L);
- •Expected length of hospital stay of at least 10 days.
排除标准
- •Clinically or microbiologically documented infection;
- •Patient already receives broad spectrum antibiotic therapy;
- •Any critical illness for which Intensive Care Unit treatment is required;
- •SOFA score ≥ 11;
- •Longstanding neutropenia (>21 days) prior inclusion;
- •Previous enrolment in this study;
- •Not able to provide written informed consent;
- •Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol;
- •Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
研究组 & 干预措施
Short treatment group
Empirical broad-spectrum antibiotics (EBAT) as per local protocol:
- Meropenem 3 x 1(/2) g IV; OR
- Piperacilline-Tazobactam 4 x 4 g IV; OR
- Cefepime 3 x 2 g IV; OR
- Ceftazidim 3 x 2 g IV
Short treatment group: EBAT will be discontinued:
- After 3x24 hours;
- Irrespective of presence of fever; AND
- If no clinical of microbiological infection is documented.
干预措施: Comparison short vs extended EBAT treatment group (Other)
Extended treatment group
Empirical broad-spectrum antibiotics (EBAT) as per local protocol:
- Meropenem 3 x 1(/2) g IV; OR
- Piperacilline-Tazobactam 4 x 4 g IV; OR
- Cefepime 3 x 2 g IV; OR
- Ceftazidim 3 x 2 g IV
Extended treatment arm: EBAT will be continued:
- At least 5x24 hours;
- Until afebrile (TMT<38.0°C) for at least 5 consecutive days; OR
- Until resolution of neutropenia (ANC >0,5 x109/L); OR
- Until they have been treated 10 days, whatever comes first.
干预措施: Comparison short vs extended EBAT treatment group (Other)
结局指标
主要结局
Absence of a serious medical complication (SMC) following 42 days after randomisation. SMC is defined as: Death; and/or ICU admission; and/or Septic shock requiring vasopressive therapy.
时间窗: 42 days
次要结局
- Number of readmissions within 42 days(42 days)
- Incidence of candidemia(42 days)
- Length of hospital stay in the first 42 days after randomization(42 days)
- Number of patients admitted to the ICU within 42 days after randomisation(42 days)
- Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE(42 days)
- Clinically documented infections(42 days)
- Total days of non-prophylactic antibiotics given to the patient at engraftment(42 days)
- Incidence, severity and duration of diarrhea(42 days)
- Number of patients in the short treatment arm with ongoing fever at time of EBAT stop(42 days)
- Incidence of bacteraemia within 42 days after randomisation(42 days)
- Total numbers of antibiotic switches before neutrophil recovery(42 days)
- Incidence of Clostridium difficile infection(42 days)
- Duration of hospitalization(42 days)
- Number of documented bacterial infections(42 days)
- Incidence of acute GVHD (grade II or higher) in the transplanted study population(42 days)