Asymptomatic Bacteriuria in Pregnancy in Low- and Middle-Income Countries-ABLE Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,134
- 试验地点
- 2
- 主要终点
- Small Vulnerable Newborn or Stillbirth defined by the occurrence of any of the following
研究概览
简要总结
Background: About 35 million pregnancies worldwide each year result in the birth of a small vulnerable newborn (SVN, defined by the occurrence of preterm birth [PTB] or small for gestational age [SGA]) or in stillbirth (SB). SVNs experience a higher rate of complications than those who are born at term and at a weight appropriate for gestational age. Prior studies have suggested that screening for asymptomatic bacteriuria during pregnancy and treating with antibiotics (nitrofurantoin) may reduce the incidence of low birth weight and/or prematurity, but with mixed results. This study explores the impact of treating asymptomatic bacteriuria during pregnancy in low- and middle-income countries on the incidence of SVN/SB, where the burden of SVN/SB is the highest and the potential impact of intervention is the greatest.
Primary Hypothesis: Among pregnant individuals with asymptomatic bacteriuria before 20 weeks’ gestation, the incidence of SVN/SB will be lower in pregnant individuals receiving a course of oral nitrofurantoin monohydrate/macrocrystals than among those receiving placebo.
Study Design: Parallel-arm, double-blind, placebo-controlled, 2:1 allocation, randomized controlled trial
Population: Pregnant individuals (n=1,134 total) with asymptomatic bacteriuria at initial visit during pregnancy, who enroll in the Maternal Newborn Health Registry and are followed through delivery at study hospitals, birthing facilities or home, in 7 sites (Bangladesh, India [2 sites], Pakistan, Democratic Republic of Congo, Zambia and Guatemala).
Treatment Arms:
Intervention: 7-day course of oral nitrofurantoin monohydrate/macrocrystals
Comparison: 7-day course of oral identical-appearing placebo
Primary Endpoint:
a. SVN/SB, defined by the occurrence of any of the following:
b. PTB, defined by birth <37 completed weeks gestation;
c. SGA, defined by birth weight <10th percentile of weight for gestational age, using INTERGROWTH 21st international, sex-specific birthweight standards; or
d. SB, defined by fetal loss or SB > 22 weeks’ gestation.
Secondary Endpoints:
Maternal
- Clinical endpoints
a. Symptomatic maternal lower urinary tract infection (randomization to delivery)
b. Maternal pyelonephritis (randomization to delivery)
c. Other serious maternal infections (at least one of intraamniotic infection, post-partum (PP) endometritis, perineal wound infection, cesarean wound infection, or sepsis) (randomization to 42 days PP)
d. Preeclampsia (randomization to 42 days PP)
e. Maternal antepartum (AP) hospitalization (randomization to 42 days PP)
f. Maternal PP hospitalization (delivery to 42 days PP)
g. Maternal death (randomization to 42 days PP)
- Safety endpoints
a. Serious adverse events (randomization to 42 days PP)
Neonatal
***1.***Clinical endpoints
a. Gestational age at birth
b. PTB, defined by birth <37 completed weeks gestation
c. SGA, defined by birth weight <10th percentile of weight for gestational age, using INTERGROWTH 21st international, sex-specific birthweight standards
d. SB, defined by fetal loss or SB > 22 weeks’ gestation
e. Neonatal infections (at least one of sepsis, pneumonia, or meningitis) (birth to 42 days PP)
f. Early neonatal death (birth to 7 days of age)
g. Neonatal death (birth to 28 days of age)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 49.00 Year(s)（—）
- 性别
- Female
入选标准
- •Individuals who meet the following criteria are eligible for randomization Enrolled in Global Network Maternal Newborn Health Registry Established pregnancy more than or equal to 12 weeks and less than or equal to 20 weeks GA by last menstrual period and/or clinical assessment and/or ultrasonography Age: 18 years to 49 years Expressed understanding of study procedures and willingness to complete screening, randomization, study drug administration and follow-up Able to provide informed consent Presence of a single bacterial isolate (more than 10 to the power of 5 colony forming unit (CFU)/mL) in urine at enrollment Intent to remain in study area for at least 42 days post partum.
排除标准
- •Individuals who meet any of the following criteria are not eligible for randomization Gestational age less than 12 weeks or more than 20 weeks Received treatment with any antibiotic within 14 days before screening visit Current symptoms of UTI History of allergy to nitrofurantoin Pregnancy loss / miscarriage prior to randomization Currently taking magnesium-containing antacid Any illness / condition (e.g., anemia, diabetes, renal disease, pulmonary disease) requiring immediate medical care per site PI assessment Enrollment in another trial that per the study Manual of Operation will impact this trial.
结局指标
主要结局
Small Vulnerable Newborn or Stillbirth defined by the occurrence of any of the following
时间窗: Preterm birth defined by birth less than 37 completed weeks of gestation | Small for Gestational Age and Still Birth at the time of birth
Preterm birth,
时间窗: Preterm birth defined by birth less than 37 completed weeks of gestation | Small for Gestational Age and Still Birth at the time of birth
Small for Gestational Age defined by birth weight less than 10th percentile of weight for gestational age using INTERGROWTH 21st international, sex-specific birthweight standards or Still birth, defined by fetal loss or Still birth more than 22 weeks gestation
时间窗: Preterm birth defined by birth less than 37 completed weeks of gestation | Small for Gestational Age and Still Birth at the time of birth
次要结局
- Maternal post-partum hospitalization(Delivery to 42 days post-partum)
- Maternal death(Randomization to 42 days post-partum)
- Maternal Serious adverse events(Randomization to 42 days post-partum)
- Gestational age at birth(At the time of birth)
- Preterm birth, defined by birth less than 37 completed weeks gestation(At the time of birth)
- Symptomatic maternal lower Urinary Tract Infection(Randomization to delivery)
- Maternal pyelonephritis(Randomization to delivery)
- Other serious maternal infections (at least one of intraamniotic infection, Post partum endometritis, perineal wound infection, cesarean wound infection, or sepsis)(Randomization to 42 days post-partum)
- Preeclampsia(Randomization to 42 days post-partum)
- Maternal ante-partum hospitalization(Randomization to 42 days post-partum)
- Small for Gestational Age, defined by birth weight less than 10th percentile of weight for gestational age, using INTERGROWTH 21st international, sex-specific birthweight standards(At the time of birth)
- Still birth defined by fetal loss or SB more than 22 weeks gestation(At the time of birth)
- Neonatal infections (at least one of sepsis, pneumonia, or meningitis)(Birth to 42 days post-partum)
- Early neonatal death(Birth to 7 days of age)
- Neonatal death(Birth to 28 days of age)
- Number of subsequent courses of antibiotics administered to the mother(After completion of study drug until delivery of the newborn)
研究者
Dr Shivaprasad S Goudar
KLE Academy of Higher Education and Researchs J N Medical College