A Randomized Trial of 17-Hydroxyprogesterone Caproate (17P) to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy

17-羟基孕酮己酸酯 (17P) 减少妊娠期接受抗逆转录病毒治疗的妇女早产的随机试验

• 批准号: 9271471
• 负责人: JEFFREY Samuel Allen STRINGER
• 金额: $ 51.39万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-27 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271471
• 关键词: 17p; 37 weeks gestation; AIDS/HIV problem; Africa; Africa South of the Sahara; Anti-Retroviral Agents; Asia; Biometry; Birth; CD4 Positive T Lymphocytes; Caring; Cell Count; Cervical; Cervix Uteri; Cessation of life; Conceptions; Consent; Country; Developing Countries; Diagnosis; Enrollment; Epidemic; FDA approved; Fetal Growth Retardation; Gestational Age; HIV; HIV Infections; HIV antiretroviral; Histopathology; Hydroxyprogesterone; Immune; Individual; Infant; Inflammation; Inflammatory; Injection of therapeutic agent; Intervention; Intramuscular; Intramuscular Injections; Length; Live Birth; Malawi; Masks; Mediating; Mothers; Neonatal Mortality; Outcome; Participant; Pathology; Patients; Perinatal; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Placebo Control; Placebos; Policies; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnant Women; Premature Birth; Price; Progesterone; Progestins; Prophylactic treatment; Public Health; Randomized; Randomized Clinical Trials; Recording of previous events; Research Infrastructure; Risk; Site; Survivors; Techniques; Testing; Time; Ultrasonography; United States; Variant; Vertical Disease Transmission; Woman; Work; Zambia; antiretroviral therapy; base; cohort; cost effective; disability; experience; extreme prematurity; fetal; follow-up; high risk; improved; mortality; neonatal death; neonate; premature; prenatal; prevent; primary outcome; prophylactic; prospective; randomized trial; screening; secondary outcome; standard of care; stillbirth

ABSTRACT A Trial of 17-Hydroxyprogesterone Caproate (17P) to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy Preterm birth (PTB) is the most common cause of neonatal death worldwide and the second leading cause of under-5 mortality. Maternal HIV complicates 1.5 million pregnancies per year and increases the risk of PTB. While antiretroviral therapy (ART) in pregnancy can virtually eliminate mother-to-child transmission, it increases the risk of PTB beyond the excess risk attributable to HIV itself. This has led us to the untenable place where, in too many instances, the price of stopping perinatal HIV is prematurity-related neonatal death. Prenatal progesterone reduces the risk of PTB among women diagnosed with shortening of the uterine cervix and among women who have experienced a prior spontaneous PTB. It is standard of care for these indications in the United States. This application has two specific aims. In Aim 1, we propose a placebo-controlled, double-masked randomized clinical trial of the drug 17-hydroxyprogesterone (17P) to prevent PTB among HIV-infected pregnant women initiating or continuing antiretroviral drug therapy (ART) in Malawi and Zambia. Because stillbirth and preterm birth are competing risks, the trial's primary outcome will be a composite of live birth prior to 37 weeks gestation or stillbirth at any gestational age. The trial is powered to assess whether 17P has the same prophylactic efficacy among HIV-infected women as it does among women with a prior PTB (an indication for which it is FDA approved). Our specific hypothesis is that 17P will reduce the primary outcome by 38% (i.e., from 24% to 15%). The trial will randomly allocate 800 consenting women in a 1:1 ratio to receive weekly intramuscular injections of either active drug or matched placebo. We will follow women through pregnancy and mother-infant pairs to 42 days postpartum. In Aim 2 of this application, we will study the relationship between timing of ART initiation and the risk of PTB. Our hypothesis is that HIV-infected women who start ART during pregnancy will have higher rates of PTB compared to women who enter antenatal care on ART started prior to conception. This trial will take advantage of longstanding partnerships and robust research infrastructure in Malawi and Zambia. If our primary hypothesis is confirmed – that 17P works as well among HIV infected women as it does among those with a prior preterm birth – we will have identified an intervention that could prevent as many as 70,000 preterm births per year worldwide.

摘要 17-羟孕酮己酸酯（17 P）减少接受17-羟孕酮治疗的妇女早产的试验 妊娠期抗逆转录病毒治疗 早产（PTB）是世界范围内新生儿死亡的最常见原因，也是新生儿死亡的第二大原因。 5岁以下儿童死亡率。孕产妇艾滋病毒每年使150万例妊娠复杂化，并增加了PTB的风险。 虽然妊娠期抗逆转录病毒疗法（ART）几乎可以消除母婴传播， 增加了PTB的风险，超出了HIV本身的过度风险。这使我们陷入了一个站不住脚的境地， 在太多情况下，阻止围产期艾滋病毒的代价是与早产有关的新生儿 死亡 产前孕激素可降低宫颈缩短妇女的PTB风险 以及既往有过自发性PTB的女性。这是这些适应症的标准治疗 在美国 这项申请有两个具体目标。在目标1中，我们提出了一个安慰剂对照，双盲随机 17-羟孕酮（17 P）预防HIV感染孕妇肺结核的临床试验 在马拉维和赞比亚开始或继续进行抗逆转录病毒药物治疗。因为死胎和早产 出生是竞争性风险，试验的主要结局将是37周前活产的复合结果 任何胎龄的妊娠或死胎。该试验旨在评估17 P是否具有相同的 在HIV感染女性中的预防效果与在既往患有PTB的女性中一样（ 经FDA批准）。我们的具体假设是，17 P将使主要结局降低38%（即， 从24%到15%）。该试验将以1：1的比例随机分配800名同意的女性， 肌肉注射活性药物或匹配的安慰剂。我们将跟踪妇女怀孕期间的情况 和母婴配对至产后42天。在本申请的目标2中，我们将研究 开始抗逆转录病毒治疗的时间和肺结核的风险之间的关系。我们的假设是，开始抗逆转录病毒治疗的艾滋病毒感染妇女 与接受抗逆转录病毒治疗的产前护理的妇女相比， 在怀孕之前。 这项试验将利用马拉维的长期伙伴关系和强大的研究基础设施， 赞比亚.如果我们的主要假设得到证实-17 P在感染艾滋病毒的妇女中的作用与它一样好， 在那些先前早产的人中，我们将确定一种干预措施， 全球每年有7万例早产。