Development and testing of the Novocuff device to prevent infant morbidities and mortalities caused by preterm birth.

开发和测试 Novocuff 装置，以预防早产引起的婴儿发病和死亡。

• 批准号: 10761418
• 负责人: Donald Lee
• 金额: $ 29.56万
• 依托单位: NOVOCUFF INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10761418
• 关键词: 37 weeks gestation; Accounting; Address; Age; American College of Obstetricians and Gynecologists; Anatomy; Applications Grants; Atopobium vaginae; Birth History; Black race; Businesses; California; Cause of Death; Cervical; Cervical Cerclage; Cervix Uteri; Clinical; Clinical Treatment; Clinical Trials; Development; Devices; Engineering; Environment; Evidence based treatment; FDA approved; Fetal Viability; Fetus; Future; Gestational Age; Grant; Health Care Costs; Hospital Costs; Human Resources; Infant; Infant Mortality; Institution; Intramuscular; Length; Low income; Maternal Health; Mechanics; Medical Device; Modality; Modeling; Newborn Infant; Nulliparity; Operative Surgical Procedures; Patients; Pessaries; Phase; Physicians; Population; Population Group; Positioning Attribute; Preclinical Testing; Pregnancy; Pregnancy loss; Premature Birth; Progesterone; Prolonged Pregnancy; Provider; Randomized Controlled Clinical Trials; Readiness; Recommendation; Recording of previous events; Risk; Risk Factors; Risk Reduction; Second Pregnancy Trimester; Small Business Innovation Research Grant; Specialist; Surgical sutures; Testing; Tissues; Transvaginal Ultrasound; Trauma; Twin Multiple Birth; Uncertainty; United States; Vagina; biomaterial compatibility; clinic ready; clinical practice; clinical trial readiness; commercialization; cost; design; design verification; education research; efficacy evaluation; high risk population; improved; infant death; infant morbidity; infant morbidity/mortality; maternal morbidity; minimally invasive; pathogen; pharmacologic; phase 1 study; pre-clinical; pregnant; prevent; skills training; social factors; vaginal microbiota

PROJECT SUMMARY/ABSTRACT Preterm birth (PTB), delivery < 37 weeks gestational age (GA), is the leading cause of death for infants under the age of one. In addition, PTB is associated with costs of $26 billion dollars per year in the United States (US) - accounting for half of all infant-related hospitalization costs. One of the greatest risk factors for spontaneous PTB, which comprises 70% of all PTBs, is a short cervix (i.e. shortened cervical length on transvaginal ultrasound). There is currently no FDA approved device that addresses the 360,000 annual spontaneous PTBs in the US; there are also no consistently proven pharmacologic therapies. The only effective mechanical treatment option available is a cerclage, a surgical procedure involving suturing the cervix closed. There are however, numerous limitations to cerclages: 1) as a surgical procedure it requires access to an operative room, personnel, and its associated costs, 2) it is only be performed up to fetal viability (22-24 weeks GA), 3) it requires a highly skilled trained provider, usually a specialist 4) it is not recommended for patients with multiple gestations 5) it is indicated (and proven beneficial) only in patients with a shortened cervical length and prior PTB/2nd trimester pregnancy loss and 6) while it may be performed in other populations emergently for cervical dilation as a rescue cerclage, has shown no consistent benefit. Novocuff Inc., a California-based small business, is developing an easy to use, minimally invasive, non-surgical device intended to reduce the risk of spontaneous PTB. The Novocuff device is designed to support the cervix, assist in maintaining cervical length, and adjust the angle of the cervix to decrease the forces that lead to cervical shortening. Preliminary benchtop studies have demonstrated Novocuff’s ability to apply circumferential compression around a cervix model without causing trauma to the cervical tissue. The risk profile of the Novocuff device is considerably lower than the cerclage since it is non-surgical, not embedded in the cervix, and can be placed/adjusted in an office setting. The decreased risk profile would not only allow it to be used in lieu of a cerclage, but also for those in whom a cerclage is not indicated (i.e. twins, nulliparas), and >24 weeks GA, increasing treatment options for physicians and patients. Novocuff has the support of key opinion leaders at respected educational research institutions. These physicians have provided valuable clinical input regarding the design and application of the Novocuff device and will assist in verifying the design during any future benchtop studies. The next step in design verification and the key focus of the proposed Phase I project, is to determine the feasibility and clinical readiness of the Novocuff device. Our specific aims are to 1) test that the Novocuff device can apply comparable forces to the cervix as a surgical cerclage, 2) test Novocuff biocompatibility and bioburden and 3) test that the Novocuff device passes all functional requirements. At the end of Phase I, Novocuff will have completed all the necessary preclinical testing to demonstrate mechanical readiness for a clinical trial. Phase II efforts will focus on supporting an FDA submission. The broad, long-term objective of this Phase I grant application is to improve clinical treatment options that bridge the gap between potentially viable and healthy newborns, decrease the risk of PTB, and to reduce infant mortality, with its associated effects on maternal health.

项目总结/摘要 早产（PTB），分娩< 37周胎龄（GA），是婴儿死亡的主要原因， 一岁。此外，PTB每年在美国（US）与260亿美元的成本相关-会计 占婴儿住院费用的一半自发性PTB的最大风险因素之一，包括 70%的PTB是宫颈短（即经阴道超声显示宫颈长度缩短）。 目前没有FDA批准的器械可以解决美国每年360，000例自发性PTB; 也没有经过一致验证的药物疗法。唯一有效的机械治疗方法是 环扎术，一种将子宫颈封闭的外科手术。然而，有许多限制， 环扎术：1）作为一种外科手术，它需要进入手术室，人员及其相关费用，2）它是 仅在胎儿存活期（GA 22-24周）内进行，3）它需要训练有素的高技能提供者，通常是 专家4）不建议多胎妊娠患者使用5）仅适用于（且已证明有益） 宫颈长度缩短和既往PTB/妊娠中期流产的患者，以及6）虽然可能在 其他人群紧急进行宫颈扩张作为补救环扎术，没有显示出一致的益处。 Novocuff Inc.，一家总部位于加州的小企业，正在开发一种易于使用，微创，非手术 预期用于降低自发性PTB风险的器械。Novocuff装置设计用于支撑宫颈， 保持宫颈长度，并调整宫颈角度，以减少导致宫颈缩短的力。 初步实验室研究表明，Novocuff能够在患者周围施加周向压缩 子宫颈模型，而不会对子宫颈组织造成创伤。Novocuff器械的风险特征显著较低 因为它是非手术的，不嵌入子宫颈，并且可以在办公室环境中放置/调整。 降低的风险状况不仅允许它用于代替环扎术，而且也适用于那些环扎术 无适应症（即双胞胎，初产妇）和>24周GA，增加了医生和患者的治疗选择。 Novocuff得到了受人尊敬的教育研究机构的关键意见领袖的支持。这些医生 提供了关于Novocuff器械设计和应用的有价值的临床输入，并将协助 在任何未来的实验室研究中验证设计。设计验证的下一步和 拟定的I期项目旨在确定Novocuff器械的可行性和临床就绪性。我们的具体目标 是为了1）测试Novocuff器械可以向宫颈施加与外科环扎术相当的力，2）测试Novocuff 生物相容性和生物负载; 3）测试Novocuff器械是否通过所有功能要求。结束时 第一阶段，Novocuff将完成所有必要的临床前试验，以证明机械准备就绪， 临床试验第二阶段的工作重点是支持FDA提交。第一阶段的广泛、长期目标 拨款申请是为了改善临床治疗方案，弥合潜在可行性和健康之间的差距 这将有助于降低新生儿的死亡率，减少肺结核的风险，并降低婴儿死亡率及其对孕产妇健康的相关影响。