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.

项目概要/摘要 早产 (PTB)、胎龄 < 37 周 (GA) 的分娩是婴儿死亡的主要原因 一岁。此外，在美国 (US)，PTB 每年产生 260 亿美元的成本 - 会计 占所有婴儿相关住院费用的一半。自发性 PTB 的最大危险因素之一包括 所有 PTB 中的 70% 是子宫颈短（即经阴道超声检查显示子宫颈长度缩短）。 目前还没有 FDA 批准的设备可以解决美国每年 360,000 例自发性 PTB 的问题；那里 也没有经过一致证明的药物疗法。唯一有效的机械治疗选择是 环扎术，一种涉及缝合子宫颈的外科手术。然而，存在许多限制 环扎术：1) 作为一种外科手术，需要进入手术室、人员及其相关费用，2) 仅在胎儿存活（GA 22-24 周）时进行，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) 仅在以下情况下适用（并证明有益）： 宫颈长度缩短且既往有 PTB/妊娠中期流产的患者，以及 6) 其他人群紧急进行宫颈扩张作为挽救性环扎术，但并未显示出一致的益处。 Novocuff Inc. 是一家总部位于加利福尼亚州的小型企业，正在开发一种易于使用、微创、非手术的方法 旨在降低自发性 PTB 风险的装置。 Novocuff 装置旨在支撑子宫颈，协助 保持宫颈长度，并调整宫颈角度以减少导致宫颈缩短的力量。 初步台式研究表明 Novocuff 能够在物体周围施加圆周压缩 宫颈模型不会对宫颈组织造成创伤。 Novocuff 装置的风险状况要低得多 与环扎术相比，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使其可以用来代替环扎术，而且也适用于那些需要进行环扎术的人。 未指出的（即双胞胎、未产妇）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关键意见领袖的支持。这些医生 就 Novocuff 装置的设计和应用提供了宝贵的临床意见，并将协助 在任何未来的台式研究中验证设计。设计验证的下一步和重点 拟议的第一阶段项目是确定 Novocuff 装置的可行性和临床准备情况。我们的具体目标 1) 测试 Novocuff 装置是否可以向子宫颈施加与环扎手术相当的力，2) 测试 Novocuff 生物相容性和生物负载，以及 3) 测试 Novocuff 装置是否满足所有功能要求。结束时 第一阶段，Novocuff 将完成所有必要的临床前测试，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 拨款申请旨在改善临床治疗方案，弥合潜在可行与健康之间的差距 新生儿，降低 PTB 风险，并降低婴儿死亡率及其对孕产妇健康的相关影响。