Background: We describe enrollment and accrual challenges in the “Promoting Maternal and Infant Survival Everywhere” (PROMISE) trial conducted in resource-limited countries, as well as the challenges in transitioning participants from the antepartum to the postpartum components of the study. Methods: PROMISE was a large multi-national randomized controlled trial of the safety and efficacy of interventions to reduce perinatal transmission of HIV-1 (HIV) during pregnancy and breastfeeding and of interventions to preserve maternal health after cessation of perinatal transmission risk. The PROMISE study included two protocols for HIV-infected pregnant women in resource-limited countries who intended to either breastfeed or formula-feed their infants and did not meet country criteria for antiretroviral treatment. The PROMISE breastfeeding protocol (1077BF) used a sequential randomization design with up to three randomizations (Antepartum, Postpartum, and Maternal Health). The PROMISE formula-feeding protocol (1077FF) had two randomizations (Antepartum and Maternal Health). Women presenting to the clinic during early or active labor or in the immediate postpartum period were registered as Late Presenters and screened to determine whether eligible to participate in the Postpartum randomization. Results: The study was conducted at 14 sites in seven countries and opened to enrollment in April 2011. A total of 3259 pregnant women intending to breastfeed and an additional 284 pregnant women intending to formula feed were randomized in the Antepartum component. A total of 204 Late Presenters were registered during labor or after delivery. Enrollment was high among breastfeeding women (representing 96% of the target of 3400 women) but was lower than expected among women intending to formula feed (28% of 1000 expected) and late-presenting women (8% of 2500 expected). The successful overall enrollment and final primary study analyses results were attributed to substantial preparation before the study opened, collaboration among all stakeholders, close study monitoring during implementation and the flexibility to change and streamline the protocol. Conclusions: Experiences from the PROMISE study illustrate the challenges of enrolling in longer term studies in the setting of rapidly evolving prevention and treatment standards priorities. The lessons learned will help the community, site investigators, and study coordinators in the design and implementation of future clinical trials.

中文翻译：

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国际孕产妇儿科和青少年艾滋病临床试验 (IMPAACT) 网络针对资源有限地区的 PROMISE 试验的招募和过渡挑战

背景：我们描述了在资源有限国家进行的“促进母婴生存无处不在”（PROMISE）试验中的入学和应计挑战，以及将参与者从研究的产前部分过渡到产后部分的挑战。方法：PROMISE 是一项大型多国随机对照试验，研究干预措施在怀孕和哺乳期间减少 HIV-1 (HIV) 围产期传播的安全性和有效性，以及在围产期传播风险停止后保护孕产妇健康的干预措施的安全性和有效性。PROMISE 研究包括两项针对资源有限国家的 HIV 感染孕妇的方案，这些孕妇打算母乳喂养或配方喂养婴儿，但不符合国家抗逆转录病毒治疗标准。PROMISE 母乳喂养方案 (1077BF) 使用最多三个随机化（产前、产后和产妇健康）的顺序随机化设计。PROMISE 配方奶喂养方案 (1077FF) 有两个随机分组（产前和产妇健康）。在早产或活跃分娩期间或在产后即刻到诊所就诊的妇女被登记为晚就诊者并进行筛选以确定是否有资格参与产后随机分组。结果：该研究在 7 个国家的 14 个地点进行，并于 2011 年 4 月开放招募。共有 3259 名打算母乳喂养的孕妇和另外 284 名打算母乳喂养的孕妇被随机分配到 Antepartum 部分。共有 204 名迟到者在分娩期间或分娩后登记。母乳喂养妇女的入学率很高（占目标 3400 名妇女的 96%），但在打算进行配方喂养的妇女（预计 1000 名中的 28%）和晚就诊妇女（预计 2500 名中的 8%）中低于预期。成功的整体注册和最终的主要研究分析结果归因于研究开始前的大量准备、所有利益相关者之间的合作、实施过程中的密切研究监控以及改变和简化协议的灵活性。结论：来自 PROMISE 研究的经验说明了在快速发展的预防和治疗标准优先事项的设置中参加长期研究的挑战。吸取的经验教训将有助于社区、现场调查员和研究协调员设计和实施未来的临床试验。