Levonorgestrel IUD for Emergency Contraception & Same-Day Start Study

项目摘要 本次更新申请建立在我们成功的RAPID EC（评估宫内妊娠的RCT）基础上 紧急避孕装置）试验，该试验证明左炔诺孕酮（LNG）52 mg IUD是 对紧急避孕（EC）有效，且不劣于铜T380 A用于EC。在RAPID EC试验中 317例LNG IUD EC使用者中有1例妊娠（妊娠风险为0.3%，95%CI为0 ~ 1.7%）。我们 在《新英格兰医学杂志》上发表了这项研究结果，几个月后， 美国联邦（PPFA）国家医学委员会利用我们的数据采用新的避孕保健 指南今天，超过600+ PPFA健康中心在美国提供液化天然气52毫克宫内节育器的个人与 2种新情况的妊娠试验阴性：a）EC：无保护性交后5天内和B）非EC 在月经周期的任何时间点，无论最近是否有无保护的性交，都应在同一天开始。但 LNG 52 mg IUD处方信息和CDC、WHO和ACOG临床指南，指导临床 PPFA以外的护理，目前不建议在这两种新情况下安置。当前 指南建议那些不在月经周期的前7天内， 周期中的性交（UPI）必须延迟LNG IUD放置，并在下一次月经开始后返回。这 造成了进入障碍，增加了意外怀孕的风险。 我们的目标是通过确定LNG 52的有效性来评估RAPID EC发现的可重复性 mg IUD，以防止EC妊娠，并在现实世界中的同一天开始，用户选择他们的 治疗（而不是像RAPID EC试验那样随机分配）。以正义之道， 专家，我们将在更大，更多样化的人群中测试可重复性和普遍性，以评估 是否应修订执业准则和护理标准。为了实现这一目标，我们将招募1，404名 参与者在8个PPFA分支机构与三种情况之一，目前的指导方针限制访问，但数据 支持低怀孕风险。这三组是：1）EC定期周期组- LNG IUD EC用户， 在5天内有UPI，并有已知的末次月经期和规律的月经周期（纳入标准 来自RAPID EC试验），2）当天开始（非EC）组-选择LNG IUD避孕的人 月经开始后> 7天，5天内未报告UPI，3）EC未知或不规则周期 组-选择LNG IUD治疗EC的个体，没有已知的末次月经期或定期月经 周期所有组将进行非劣效性比较。第1组将与来自 LNG IUD参与RAPID EC试验。将第2组和第3组与第1组进行比较。对于所有群体，我们 预计一个月的怀孕率<1%。关于LNG 52 mg IUD的严格、可重现和可推广数据 使用EC或同一天开始从更异质的人群可以告知数百万人的IUD 全球访问。

PROJECT SUMMARY This renewal application builds on our successful RAPID EC (RCT Assessing Pregnancy with Intrauterine Devices for Emergency Contraception) trial, which demonstrated that the levonorgestrel (LNG) 52 mg IUD is effective for emergency contraception (EC) and noninferior to the copper T380A for EC. In the RAPID EC trial there was 1 pregnancy among 317 LNG IUD EC users, (pregnancy risk of 0.3%, 95% CI 0-1.7%). We published the study results in the New England Journal of Medicine, and within months Planned Parenthood Federation of America’s (PPFA) National Medical Committee used our data to adopt new contraceptive care guidelines. Today, over 600+ PPFA health centers in the U.S. offer the LNG 52 mg IUD to individuals with a negative pregnancy test for 2 new situations: a) EC: within 5 days of unprotected intercourse and b) non-EC same-day start at any point in the menstrual cycle regardless of recent unprotected intercourse. However, the LNG 52 mg IUD prescribing information and CDC, WHO, and ACOG clinical guidelines, which guide clinical care outside of PPFA, currently do not recommend placement in either of these 2 new situations. The current guidelines recommend that those not within the first 7 days of the menstrual cycle and report any unprotected intercourse (UPI) in the cycle must delay LNG IUD placement and return after the next menses starts. This creates an access barrier and increases the risk of undesired pregnancy. Our goal is to assess reproducibility of RAPID EC’s findings by determining the effectiveness of the LNG 52 mg IUD to prevent pregnancy for EC and same-day start in real-world settings where users select their treatment (and are not randomized to it as in the RAPID EC trial). With guidance from a Reproductive Justice expert, we will test reproducibility and generalizability in a larger, more diverse population, to assess whether practice guidelines and standards of care should be revised. To accomplish this we will enroll 1,404 participants at 8 PPFA affiliates with one of three situations where current guidelines limit access but data support low pregnancy risk. The three groups are: 1) EC regular-cycle group - LNG IUD EC users who have had UPI within 5 days and have a known last menstrual period and regular menstrual cycles (inclusion criteria from the RAPID EC trial), 2) Same-day start (not EC) group - people choosing the LNG IUD for contraception > 7 days after onset of menses without reported UPI within 5 days, 3) EC unknown- or irregular- cycle group - individuals choosing the LNG IUD for EC without a known last menstrual period or regular menstrual cycle. All groups will undergo noninferiority comparisons. Group 1 will be compared to the historical data from the LNG IUD participants in the RAPID EC trial. Group 2 and 3 will be compared to group 1. For all groups we expect one-month pregnancy rates <1%. Rigorous, reproducible, and generalizable data on LNG 52 mg IUD use for EC or same-day start from more heterogenous populations could inform millions of people’s IUD access globally.