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: 10582717
• 负责人: Anna Palatnik
• 金额: $ 50.19万
• 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/10582717
• 关键词: Acute; Address; Agreement; Anxiety; Birth; Birth trauma; Black race; Cesarean section; Clinical; Complications of Diabetes Mellitus; Data; Diabetes Mellitus; Disease Management; Disparity; Ethnic Origin; Ethnic Population; 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; active control group; adverse outcome; 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; racial population; response; safety assessment; 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.

项目摘要/摘要 妊娠糖尿病（GDM）每年使10％的妊娠复杂化，并且作为一个 肥胖流行的结果。 GDM和由此产生的母体高血糖导致了明显的母亲和 新生儿并发症可以通过血糖控制减少。所需的治疗程度是基于 母体血糖对医学营养疗法（MNT）和运动的反应；至少有30-50％的患者 将失败MNT和运动的初步试验，随后需要药物治疗。至关重要的是， 尚未确定构成MNT和运动的不成功的定义。 因此，药物治疗的主动性是提供者的酌处权，实践中有很大差异。我们 最近在全国对452名母亲医学提供商（MFMS）的调查中证明了这种差异 > 80％的MFM要求基于证据的建议指导药物治疗的开始。我们 还表明，早期的药物治疗倡议以20％升高的葡萄糖值改善复合材料 新生儿结果。但是，这种强烈的治疗也会增加胎龄小的风险 年龄，可能会对患者报告的结果产生负面影响，例如焦虑，抑郁和压力。 最后，缺乏药物治疗计划的标准化指南可能引入偏见，并导致 种族和种族分娩的医疗保健差异。因此，迫切需要解决这一专业 在GDM的临床实践中差距，并研究了早期的效率，安全性和患者报告的结果 GDM的药物治疗计划。我们计划使用GDM和药物治疗（GAP）来解决这一差距 研究是416例GDM患者的随机对照试验，该试验将比较两个阈值（20％比40％） 胰岛素启动之前的葡萄糖值升高。我们的核心假设是早些时候开始的胰岛素， 与对照组相比，定义为20％的葡萄糖值升高，定义为葡萄糖值高40％， 将导致GDM管理中与GDM相关的不良结果和差异的减少，而无需广告 健康后果。我们的假设已根据我们的飞行员数据提出，有利于20％的阈值 用于临床结果。根据我们的调查结果，选择为40％的主动对照组证明 该MFM的75％以葡萄糖值升高40％开始药物治疗。我们将追求以下三个 具体目的：1）确定早期胰岛素启动对GDM管理对不良新生儿的影响 以及与GDM相关的母亲结果； 2）评估孕妇早期胰岛素启动的安全性 患者及其新生儿； 3）确定早期胰岛素启动对患者报告的影响 使用标准化措施和定性访谈的结果。差距研究将提供高级 GDM中药物治疗计划的证据，将对临床实践产生直接影响。如果经过证明 有效且安全的早期药物治疗计划将改善孕妇及其健康的健康 后代，将促进GDM管理的标准化。