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.
Public Health Relevance Statement: PROJECT NARRATIVE Preterm birth (PTB) is the leading cause of death for infants under the age of one, costing the United States $26 billion dollars per year, and accounting for half of all infant-related hospitalization costs. One of the primary causes of spontaneous PTB is a short or weak cervix that cannot support the pregnancy. There are limited treatment options, with limited benefit, for cervical shortening. Novocuff Inc. is developing an easy to use, minimally invasive, non-surgical device intended to prevent PTB by maintaining the cervical strength and integrity across a diverse group of populations.
Project Terms: Recommendation; Risk; Risk Factors; Surgical sutures; Sutures; Testing; Tissues; Body Tissues; Twin Multiple Birth; Twins; United States; Vagina; Vaginal; Health Costs; Healthcare Costs; Health Care Costs; Businesses; Specialist; doubt; Uncertainty; Prematurely delivering; Preterm Birth; premature childbirth; premature delivery; preterm delivery; Premature Birth; improved; cervix cerclage; uterine cervix cerclage; Cervical Cerclage; Transvaginal Ultrasound; Cervical; Clinical; Phase; randomized control clinical trial; Randomized Controlled Clinical Trials; Hospitalization cost; Hospital Costs; Mechanics; mechanic; mechanical; Intramuscular; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; infant death; death in first year of life; infant demise; infantile death; skills training; biomaterial compatibility; biocompatibility; Pregnancy loss; Modality; Devices; Human Resources; Manpower; personnel; Positioning Attribute; Position; infant morbidity; Modeling; A vaginae; A. vaginae; Atopobium vaginae; reduce risk; reduce risks; reduce that risk; reduce the risk; reduce these risks; reduces risk; reduces the risk; reducing risk; reducing the risk; risk-reducing; Risk Reduction; Provider; Population Group; Institution; preventing; prevent; Preparedness; Readiness; Low income; Address; Length; Applications Grants; Grant Proposals; Preclinical Testing; pre-clinical testing; American College of Obstetricians and Gynecologists; ACOG; Clinical Treatment; trial regimen; trial treatment; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Development; developmental; pre-clinical; preclinical; Evidence based treatment; cost; designing; design; determine efficacy; efficacy analysis; efficacy assessment; efficacy determination; efficacy examination; evaluate efficacy; examine efficacy; efficacy evaluation; pathogen; Population; Trauma; commercialization; pregnant; FDA approved; minimally invasive; clinical practice; Phase I Study; phase 1 study; infant morbidity/mortality; maternal morbidity; education research; 37 weeks completed gestation; 37 weeks gestation; high risk group; high risk individual; high risk people; high risk population; vagina microbiota; vaginal flora; vaginal microbial community; vaginal microflora; vaginal microbiota; social factors; clinical trial readiness; design verification; design validation; pharmacologic; clinic ready; clinical ready; Accounting; ages; Age; Anatomic Sites; Anatomic structures; Anatomy; Birth History; Black race; Black; California; Cause of Death; Cervix Uteri; Cervix; Uterine Cervix; Clinical Trials; Engineering; Environment; Fetal Viability; Fetus; Future; Gestational Age; Chronologic Fetal Maturity; Fetal Age; Grant; Recording of previous events; History; histories; Infant; Infant Mortality; Infant Mortality Total; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Maternal Health; Medical Device; Nulliparity; Nulliparas; Nulliparous; Patients; Pessaries; Physicians; Pregnancy; Gestation; Second Pregnancy Trimester; 2nd trimester; Midtrimester; Second Trimester; Prolonged Pregnancy; Progesterone; Corpus Luteum Hormone; Delta4-pregnene-3,20-dione; Pregn-4-ene-3,20-dione; Pregnenedione; Therapeutic Progesterone
