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: 9769543
• 负责人: JEFFREY Samuel Allen STRINGER
• 金额: $ 52.29万
• 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/9769543
• 关键词: 37 weeks gestation; AIDS/HIV problem; Africa; Africa South of the Sahara; Anti-Retroviral Agents; Asia; Biometry; Birth; CD4 Positive T Lymphocytes; Caproates; Caring; Cell Count; Cervical; Cervix Uteri; Conceptions; Consent; Country; Developing Countries; Diagnosis; Enrollment; Epidemic; FDA approved; Fetal Growth Retardation; Gestational Age; HIV; HIV Infections; HIV antiretroviral; HIV therapy; Histopathology; Hydroxyprogesterone; Immune; Individual; Infant; Inflammation; Inflammatory; Injections; Intervention; Intramuscular; Intramuscular Injections; Length; Live Birth; Malawi; Masks; Mediating; Mothers; Neonatal Mortality; Outcome; Participant; Pathology; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Placebos; Policies; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnant Women; Premature Birth; Price; Progesterone; Progestins; Prophylactic treatment; Prospective cohort; Public Health; Randomized; Randomized Clinical Trials; Recording of previous events; Research Infrastructure; Risk; Savings; Site; Survivors; Techniques; Testing; Time; Ultrasonography; United States; Variant; Vertical Disease Transmission; Woman; Work; Zambia; antenatal; antiretroviral therapy; base; cost effective; disability; effective intervention; experience; extreme prematurity; fetal; follow-up; high risk; improved; mortality; mortality risk; neonatal death; neonate; perinatal HIV; premature; prenatal; prevent; primary outcome; prophylactic; randomized trial; recruit; screening; secondary outcome; standard of care; stillbirth; virtual

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.

抽象的 17-羟基孕酮己酸酯 (17P) 减少妊娠妇女早产的试验 妊娠期抗逆转录病毒治疗 早产（PTB）是全世界新生儿死亡的最常见原因，也是导致新生儿死亡的第二大原因。 5 岁以下儿童死亡率。母亲感染艾滋病毒每年使 150 万次妊娠变得复杂，并增加了原发性结核病的风险。 虽然怀孕期间的抗逆转录病毒治疗（ART）实际上可以消除母婴传播，但 增加的 PTB 风险超出了 HIV 本身造成的超额风险。这让我们陷入了站不住脚的境地 在很多情况下，阻止围产期艾滋病毒的代价是与早产相关的新生儿 死亡。 产前黄体酮可降低诊断为宫颈缩短的女性患 PTB 的风险 以及曾经历过自发性 PTB 的女性。这是这些适应症的护理标准 在美国。 该应用程序有两个具体目标。在目标 1 中，我们提出了一种安慰剂对照、双盲随机 17-羟基孕酮 (17P) 药物预防 HIV 感染孕妇 PTB 的临床试验 在马拉维和赞比亚开始或继续抗逆转录病毒药物治疗（ART）。因为死产和早产 出生是相互竞争的风险，试验的主要结果将是 37 周前活产的综合结果 任何胎龄的妊娠或死产。该试验旨在评估 17P 是否具有相同的功能 HIV 感染妇女的预防效果与既往有 PTB 的妇女的预防效果相同（表明 这是 FDA 批准的）。我们的具体假设是 17P 将使主要结局降低 38%（即 从 24% 增至 15%）。该试验将以 1:1 的比例随机分配 800 名同意的女性，每周接受一次 肌肉注射活性药物或匹配的安慰剂。我们将跟踪女性整个怀孕期 以及母婴配对到产后 42 天。在此应用程序的目标 2 中，我们将研究以下关系 ART 开始时间和 PTB 风险之间的关系。我们的假设是，开始 ART 的 HIV 感染女性 与开始接受 ART 进行产前护理的女性相比，怀孕期间的 PTB 发生率更高 受孕前。 该试验将利用马拉维和印度的长期合作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——17P 在 HIV 感染女性中同样有效 在那些有早产史的人中——我们将找到一种干预措施，可以预防多达 全球每年有 70,000 例早产。