Gestational Diabetes and Pharmacotherapy (GAP) – A Randomized Controlled Trial Investigating Timing of Pharmacotherapy Initiation for Patients with Gestational Diabetes

妊娠糖尿病与药物治疗 (GAP) — 一项研究妊娠糖尿病患者开始药物治疗时机的随机对照试验

• 批准号: 10419944
• 负责人: Anna Palatnik
• 金额: $ 51.94万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-03 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10419944
• 关键词: Acute; Address; Agreement; Anxiety; Birth; Birth trauma; Black race; Cesarean section; Clinical; Control Groups; Data; Diabetes Mellitus; Disease Management; Ethnic Origin; Ethnic group; Exercise; Exposure to; Foundations; Frequencies; Gestational Age; Gestational Diabetes; Glucose; Goals; Guidelines; Health; Heterogeneity; Hispanic; Hyperbilirubinemia; Hyperglycemia; Hypoglycemia; Insulin; Interview; Lead; Level of Evidence; Maternal-fetal medicine; Medical Nutrition Therapy; Medication Management; Mental Depression; National Institute of Child Health and Human Development; Neonatal; Neonatal Hypoglycemia; Obesity Epidemic; Outcome; Patient Outcomes Assessments; Patients; Perinatal mortality demographics; Pharmacotherapy; Pre-Eclampsia; Pregnancy; Premature Birth; Provider; Race; Randomized; Randomized Controlled Trials; Reduce health disparities; Respondent; Risk; Safety; Self Efficacy; Small for Gestational Age Infant; Standardization; Strategic Planning; Stress; Surveys; Variant; active control; adverse outcome; base; clinical practice; clinically relevant; diabetes management; ethnic minority; evidence based guidelines; glycemic control; health care delivery; healthy pregnancy; improved; maternal hyperglycemia; maternal outcome; minority patient; neonatal outcome; neonate; offspring; perceived stress; predict clinical outcome; pregnant; prenatal exposure; prevent; racial minority; response; standardize guidelines; standardize measure; standardized care

PROJECT SUMMARY/ABSTRACT Gestational diabetes (GDM) complicates 10% of pregnancies in the US annually and is rising dramatically as a result of the obesity epidemic. GDM and the resulting maternal hyperglycemia lead to significant maternal and neonatal complications that can be reduced with glycemic control. The extent of treatment needed is based on maternal glycemic response to medical nutrition therapy (MNT) and exercise; yet at least 30-50% of patients will fail the initial trial of MNT and exercise and subsequently require pharmacotherapy. It is crucial to note, that the definition of what constitutes an unsuccessful attempt at MNT and exercise has not been established. Consequently, initiation of pharmacotherapy is at a provider’s discretion with a wide variation in practice. We recently demonstrated this variation in a national survey of 452 Maternal-Fetal Medicine providers (MFMs), with >80% of MFMs requesting evidence-based recommendations to guide initiation of pharmacotherapy. We also showed that earlier pharmacotherapy initiation at 20% elevated glucose values improved composite neonatal outcome. However, such intensified treatment could also increase the risk of a small-for-gestational age and may carry a negative impact on patient reported outcomes such as anxiety, depression and stress. Finally, the lack of standardized guidelines for pharmacotherapy initiation may introduce biases and lead to a variation in healthcare delivery by race and ethnicity. Therefore, there is a critical need to address this major gap in clinical practice of GDM and investigate the efficacy, safety, and patient reported outcomes of earlier pharmacotherapy initiation for GDM. We plan to address this gap with GDM and Pharmacotherapy (GAP) study, a randomized controlled trial of 416 patients with GDM that will compare two thresholds (20% vs. 40%) of elevated glucose values prior to insulin initiation. Our central hypothesis is that initiating insulin earlier, defined as 20% elevated glucose values, compared with controls, defined as 40% elevated glucose values, will result in reduced GDM-related adverse outcomes and disparities in GDM management, without adverse health consequences. Our hypothesis has been formulated based on our pilot data favoring the 20% threshold for clinical outcomes. The active control group chosen to be 40% based on our survey results demonstrating that 75% of MFMs start pharmacotherapy at 40% elevated glucose values. We will pursue the following three specific aims:1) Determine the effect of earlier insulin initiation for GDM management on adverse neonatal and maternal outcomes associated with GDM; 2) Assess the safety of earlier insulin initiation in pregnant patients and their neonates; and 3) Determine the effect of earlier insulin initiation on patient-reported outcomes using standardized measures and qualitative interviews. The GAP study will provide a high-level evidence for pharmacotherapy initiation in GDM and will have a direct impact on clinical practice. If proven effective and safe, earlier pharmacotherapy initiation will improve the health of pregnant patients and their offspring and will promote standardization of GDM management.

项目概要/摘要 妊娠期糖尿病 (GDM) 每年使美国 10% 的妊娠变得复杂，并且作为一种严重的疾病，这一数字正在急剧上升 GDM 的流行和由此导致的母亲高血糖导致了严重的母亲和婴儿死亡。 通过血糖控制可以减少新生儿并发症 所需治疗的程度取决于。 至少 30-50% 的患者对医学营养治疗 (MNT) 和运动有母亲血糖反应； MNT 和运动的初步试验将失败，随后需要药物治疗。值得注意的是， MNT 尝试和锻炼不成功的定义尚未确定。 经过测试，药物治疗的启动由提供者自行决定，但实践中存在很大差异。 最近在一项针对 452 名母胎医学提供者 (MFM) 的全国调查中证明了这种差异， 超过 80% 的 MFM 要求提供基于证据的建议来指导药物治疗的启动。 还表明，在血糖值升高 20% 时更早开始药物治疗可改善综合症状 然而，这种强化治疗也可能增加小于妊娠的风险。 年龄，可能会对患者报告的焦虑、抑郁和压力等结果产生负面影响。 最后，缺乏药物治疗开始的标准化指南可能会引入偏差并导致 因此，迫切需要解决这一问题。 GDM 临床实践中的差距，并调查早期治疗的有效性、安全性和患者报告的结果 我们计划通过 GDM 和药物治疗 (GAP) 来解决这一差距。 研究是一项对 416 名 GDM 患者进行的随机对照试验，比较两个阈值（20% 与 40%） 我们的中心假设是，较早开始使用胰岛素， 定义为与对照相比，血糖值升高 20%，定义为血糖值升高 40%， 将减少与 GDM 相关的不良后果和 GDM 管理中的差异，且不会产生不利影响 我们的假设是根据支持 20% 阈值的试点数据制定的。 根据我们的调查结果，选择积极对照组为 40%。 75% 的 MFM 在血糖值升高 40% 时开始药物治疗 我们将采取以下三种措施。 具体目标：1) 确定早期开始胰岛素治疗 GDM 对不良新生儿的影响 和与 GDM 相关的孕产妇结局； 2) 评估妊娠早期开始使用胰岛素的安全性； 患者及其新生儿；以及 3) 确定早期开始胰岛素治疗对患者报告的影响 GAP 研究将提供高水平的结果。 GDM 开始药物治疗的证据，如果得到证实，将对临床实践产生直接影响。 有效、安全、早期开始药物治疗将改善妊娠患者及其健康 后代，将促进GDM管理的标准化。