Selective Antibiotics When Symptoms Develop Versus Universal Antibiotics for Preterm Neonates At-risk of Early-onset Bacterial Sepsis: a Multicentric, Randomized, Controlled, Non-inferiority Trial (the SAUNA Trial)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,500
- 试验地点
- 1
- 主要终点
- Need for intravenous antibiotics for ≥ 48 hours within the 1st 7 days after randomization
研究概览
简要总结
Preterm infants are born at less than 37 weeks of pregnancy. Sometimes a break or tear in the fluid filled bag that surrounds and protects the infant during pregnancy leads to an untimely birth. This state puts the infant at risk of serious condition called sepsis. Sepsis is a condition in which body responds inappropriately to an infection. Sepsis may progress to septic shock which can result in the loss of life. Doctors give antibiotics to treat sepsis.
The goal of this research study is to find out:
- Among neonates at risk of early-onset neonatal sepsis, whether a policy of administering antibiotics selectively to a subset of at-risk infants who later develop signs of sepsis is not inferior to administering antibiotics to all at-risk infants in the 1st week of life.
- To find out if infants receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) require fewer antibiotic courses of 48 hours duration or more in the 1st week of life.
- To find out whether infants receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are significantly different with respect to a wide range of secondary outcomes (listed under "Outcomes").
详细描述
Sepsis is the major cause of neonatal mortality and early-onset neonatal sepsis (EONS) accounts for more than two-thirds of all cases of neonatal sepsis. Prolonged rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are important risk factors of EONS. There is equipoise in the published literature whether antibiotics must be immediately initiated among all preterm neonates (<35 weeks gestation) delivered following PROM or pPROM who are asymptomatic at birth or whether antibiotics can be selectively administered if and when the at-risk neonates become symptomatic.
Among neonates <35 weeks gestation born with PROM >18 hours or pPROM and who are either asymptomatic or have no symptoms of sepsis at 4 hrs postnatally (P), is selectively administering antibiotics to neonates who later develop clinical sepsis [I] compared to administering antibiotics pre-emptively to all at-risk neonates [C] non-inferior with respect to the composite outcome of "mortality and/or culture-positive sepsis and/or severe sepsis" [O] within 7 days after enrolment [T] by an absolute margin of 7% [E] in a randomized controlled trial (S)? The trial will also have a superiority outcome: "need for antibiotic treatment lasting greater than 48 hours within 7 days after enrolment". The absolute superiority margin will be 50%.
The main objectives are as follows:
- To determine whether antibiotics administered selectively to at-risk preterm neonates [<35 weeks gestation with prolonged rupture of membranes (PROM) or preterm premature rupture of membranes (pPROM)] when they develop signs of sepsis compared to administering antibiotics from birth to all at-risk neonates is non-inferior with respect to the primary outcome of "mortality or any episode of culture-positive sepsis or severe sepsis" in the 1st week of life
- To determine whether neonates receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are superior with respect to the co-primary outcome of fewer antibiotic courses of 48 hours duration or more in the 1st week of life
- To determine whether neonates receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are significantly different with respect to a wide range of secondary outcomes (listed under "Outcomes")
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
- Single (Outcomes Assessor)
盲法说明
Project staff, nurses and resident doctors looking after the neonate will not be blinded. The assessment of the primary outcome will be performed by a blinded adjudicator, who is not involved in the recruitment and monitoring of subjects. A part of the case report form (CRF) containing relevant details of all episodes of sickness in the 1st week of life will be detached from the main form and will be sent to the blinded adjudicator. This part will be linked to the main form only by a unique identification number. No patient identifiers or allocation group will be mentioned on the part sent to the blinded adjudicator.
入排标准
- 年龄范围
- 0 Hours 至 4 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Subjects will be excluded if they have any 1 of the following:
- •Life-threatening congenital malformation
- •Severe perinatal asphyxia (Apgar score <5 at 10 minutes or cord pH <7.0)
- •Clinical chorioamnionitis# [see definition below]
- •Foul-smelling liquor
- •Multiple gestation
- •Received a dose of antibiotics
- •Positive amniotic fluid culture (if performed and available prior to randomization)
- •Treating neonatologist unwilling to enroll the patient in the trial on the grounds that the patient needs antibiotics.
研究组 & 干预措施
Selective antibiotic group
Antibiotics will be administered selectively to a subset of at-risk neonates who develop clinical signs of sepsis.
干预措施: Antibiotics (Drug)
Comparison group
Antibiotics will be pre-emptively administered to all neonates at risk of sepsis.
干预措施: Antibiotics (Drug)
结局指标
主要结局
Need for intravenous antibiotics for ≥ 48 hours within the 1st 7 days after randomization
时间窗: Within 1st 7 days after randomization
Requirement for intravenous antibiotic courses whose duration is ≥ 48 hours with the onset of the course within the first 7 days after randomization. For all practical purposes, this would be equivalent to the 1st 7 days of life since participants will be randomized at about 4 hours of life.
Composite of all-cause mortality and/or any episode of culture-positive sepsis and/or severe sepsis* within the 1st 7 days after randomization
时间窗: Within 1st 7 days after randomization
Either mortality due to any cause and/or an episode of culture-positive sepsis and/or severe sepsis. These outcomes will be measured within the "1st 7 days after randomization", which for all practical purposes, is equivalent to the "1st 7 days of life" since participants will be randomized at about 4 hours of life. Hence, the duration expressed after randomization and of life will be used interchangeably for this outcome and other outcomes.
次要结局
- Sepsis-related mortality during hospital stay after randomization(During hospital stay upto 100 days after randomization)
- Composite of mortality/blood culture positive sepsis/severe sepsis within 1st 72 hours after randomization(Within first 72 hour after randomization)
- Episode of severe sepsis within 1st 7 days after randomization(Within 1st 7 days after randomization)
- Necrotizing enterocolitis, stage II-III by modified Bell's staging criteria during hospital stay(During hospital stay upto 100 days after randomization)
- Composite of mortality/blood culture positive sepsis/severe sepsis during 1st 30 days after randomization(During 1st 30 days after randomization)
- Individual components of composite outcome during 1st 30 days(During 1st 30 days after randomization)
- Necrotizing enterocolitis, stage II-III by modified Bell's staging criteria(During 1st 30 days after randomization)
- Sepsis-related mortality within 1st 72 hours after randomization(Within 1st 72 hours after randomization)
- Sepsis-related mortality within 7 day after randomization(Within 7 days after randomization)
- All-cause Mortality within 1st 7 days after randomization(During 1st 7 days after randomization)
- Blood culture-positive sepsis of any severity within 1st 7 days after randomization(Within 1st 7 days after randomization)
- Individual components of composite outcome within 1st 72 hours after randomization(Within 1st 72 hours after randomization)
- Composite of mortality/blood culture positive sepsis/severe sepsis during hospital stay(During hospital stay upto 100 days after randomization)
- Individual components of composite outcome during hospital stay(During hospital stay upto 100 days after randomization)
- Sepsis-related mortality during 1st 30 days after randomization(During 1st 30 days after randomization)
- Clinical sepsis within 1st 72 hours after randomization(Within 1st 72 hours after randomization)
- Episode of asymptomatic proven EONS within 72 hours after randomization(Within 72 hours after randomization)
- Clinical sepsis within 7 days after randomization(Within 7 days after randomization)
- Clinical sepsis during hospital stay(During hospital stay upto 100 days)
- Clinical sepsis within 1st 30 days after randomization(During 1st 30 days after randomization)
- Episode of Probable EONS within 72 hours after randomization(Within 72 hours after randomization)
- Episode of Probable EONS within 7 days after randomization(Within 7 days after randomization)
- Need for sepsis workup during 1st 72 hours after randomization(During 1st 72 hours after randomization)
- Need for sepsis workup during 1st 7 days after randomization(During 1st 7 days after randomization)
- Need for sepsis workup during 1st 30 days after randomization(During 1st 30 days after randomization)
- Need for sepsis workup during hospital stay(During hospital stay upto 100 days)
- Cumulative duration of antibiotic therapy during 1st 7 days after randomization(During 1st 7 days after randomization)
- Cumulative duration of antibiotic therapy during 1st 72 hrs after randomization(During 1st 72 hours after randomization)
- Cumulative duration of antibiotic therapy during hospital stay(During hospital stay upto 100 days after randomization)
- Duration of hospitalization(Upto 100 days)
- Episodes of healthcare associated infection during hospital stay.(From after 72 hours until 100 days during hospital stay)
- Adverse effects until day 30 after randomization(During 30 days after randomization)
- Serious adverse effects until day 30 after randomization(During 30 days after randomization)
研究者
Sourabh Dutta
Professor
Post Graduate Institute of Medical Education and Research, Chandigarh