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.

项目摘要/摘要 早产(PTB)，分娩和37周胎龄(GA)，是婴儿死亡的主要原因。 一岁。此外，结核病与美国每年260亿美元的成本有关-会计 支付所有与婴儿相关的住院费用的一半。自发性肺结核的最大危险因素之一，包括 在所有PTB中，70%是宫颈较短(即经阴道超声检查宫颈长度变短)。 目前还没有FDA批准的设备来解决美国每年36万例自发性PTB；有 也没有一直被证明的药物疗法。唯一有效的机械治疗方法是 宫颈环扎术是一种缝合宫颈的外科手术。然而，有许多限制 包扎：1)作为外科手术，它需要进入手术室、人员和相关费用，2)它是 只能进行到胎儿存活(22-24周GA)，3)它需要高技能的训练有素的提供者，通常是 专家4)不推荐用于多胎妊娠的患者5)只有在以下情况下才适用(并被证明有益) 宫颈长度缩短并有PTB/中期妊娠丢失史的患者，6)可在 其他人群紧急将宫颈扩张术作为一种抢救环扎术，并未显示出一致的益处。 总部位于加利福尼亚州的小型企业Novocuff Inc.正在开发一种易于使用、微创、非手术的 旨在降低自发性肺结核风险的装置。Novocuff设备旨在支持宫颈，帮助 保持宫颈长度，并调整宫颈角度，以减少导致宫颈缩短的力。 初步的台式研究表明，Novocuff有能力在 宫颈模型，不会对宫颈组织造成损伤。Novocuff设备的风险状况要低得多 因为它是非手术的，不嵌入宫颈，并且可以放置/调整在办公室环境中，所以比宫颈环扎要好。 减少的风险分布不仅可以用来代替环扎术，也可以用来代替环扎术。 没有指征(即双胞胎、未足月产)和24周妊娠，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关键意见领袖的支持。这些医生 为Novocuff设备的设计和应用提供了宝贵的临床意见，并将协助 在未来的任何台式研究中验证设计。设计验证的下一步和设计验证的重点 拟议的第一阶段项目是确定Novocuff设备的可行性和临床准备情况。我们的具体目标 1)测试Novocuff装置是否可以作为手术宫颈环扎术对宫颈施加类似的力，2)测试Novocuff 生物兼容性和生物负荷；3)测试Novocuff设备通过所有功能要求。在…的末尾 第一阶段，Novocuff将完成所有必要的临床前测试，以证明机械准备 临床试验。第二阶段的努力将集中在支持FDA的提交上。这一阶段的广泛、长期目标是 GRANT的申请是为了改善临床治疗选择，以弥合潜在的可行和健康之间的差距 减少新生儿肺结核的风险，降低婴儿死亡率，以及对产妇健康的相关影响。