Clinical trial NCT04301518: Prematurity Risk Assessment Combined With Clinical Interventions for Improving Neonatal outcoMEs
Official title: Prematurity Risk Assessment Combined With Clinical Interventions for Improving Neonatal outcoMEs
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Preterm Labor
Preterm Birth
Keywords: neonate
NICU
neonatal
preterm
Lead sponsor: Sera Prognostics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: High Risk Pregnancy Center, Las Vegas, Nevada
First posted: 2020-03-10
Enrollment: 6500
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To determine the efficacy and safety of a PTB prevention strategy, this study will utilize PreTRM® to prospectively stratify pregnant women with a singleton gestation into categories of risk of PTB and adverse neonatal outcomes. Subjects randomized into the PTB Prevention arm who score at or above the predetermined threshold risk will receive protocol-specified care for the prevention of PTB throughout gestation utilizing defined interventions.
Primary purpose: PREVENTION

Brief summary: This prospective, randomized, controlled study evaluates the safety and efficacy of a preterm birth (PTB) prevention strategy versus standard of care pregnancy management to reduce the incidence of adverse pregnancy outcomes.

Detailed description: Prospective subjects will be randomized to the PTB prevention strategy (PTB Prevention arm) or to standard of care management (Control arm). Subjects randomized to the preterm birth prevention strategy will receive either routine standard of care pregnancy management or a multimodal intervention protocol reserved for higher risk pregnancies based on the results of a commercially-available laboratory developed test, PreTRM® (Sera Prognostics, Inc). The intervention protocol utilizes well-established high-risk pregnancy interventions to improve maternal and neonatal health outcomes.

After enrollment, all subjects will have a blood sample collected once between 18 0/7 weeks and 20 6/7 weeks (126-146 days) of pregnancy. Subjects will be randomized 1:1 to participate in the preterm birth prevention strategy arm or standard of care for pregnancy (Control) arm. Subjects randomized to the Control arm will not receive PreTRM® test results. Subjects randomized to the PTB Prevention arm will receive the results of the PreTRM® test. Results will be reported to the subject, the study Investigator, and the subject's primary pregnancy care provider as "higher risk" of prematurity (≥15%) or "not higher" risk. Subjects with results less than 15% risk (Not Higher Risk Group) by the PreTRM® test will receive standard of care for the duration of pregnancy through hospital discharge. Subjects with results at 15% risk of preterm delivery or greater (Higher Risk Group, equivalent to 2.0-fold the general population risk) by the PreTRM® test will complete a second consenting process to receive a prespecified intervention protocol directed toward reducing risk of adverse pregnancy outcomes inclusive of neonatal morbidity and mortality. All subjects will be followed through the duration of the pregnancy and delivery, and their neonates until initial hospital discharge to assess the course of pregnancy, labor, and any related maternal or fetal complications.

Birth outcomes will be obtained, and liveborn neonates followed through hospital discharge. Readmission of infants will be assessed at 180 days, 1 year and 3 years of life using the HealthCore Integrated Research Database to evaluate longer-term outcomes and costs associated with preterm delivery.

Eligibility criteria: Inclusion Criteria

1. Subject is 18 years of age or older
2. Subject is willing and able to provide informed consent and comply with intervention if applicable
3. Subject gestational age is currently within 18 0/7 and 20 6/7 weeks using best estimated due date
4. This is a singleton intrauterine pregnancy
5. Subject has no signs and/or symptoms of preterm labor and has intact membranes
6. Subject has had a 2nd trimester anatomic ultrasound, including evaluation of cervical length, completed by the date of enrollment, but no earlier than 18
7. In the opinion of the Investigator, the subject's delivery data will be accessible within 20 business days from delivery, and neonatal data will be available for data collection purposes within 20 business days from discharge

Exclusion Criteria:

1. Subject has had a prior spontaneous preterm delivery (gestational age at birth less than 37 0/7 weeks gestation)
2. Subject has cervical length less than 25 millimeters (mm) on 2nd trimester transvaginal ultrasound at time of enrollment
3. Subject has taken progesterone or progesterone-derivative medication after 13 6/7 weeks gestation
4. Singleton gestation reduced from an original multiple gestation via embryonic reduction or vanishing twin
5. There is a known major fetal anomaly or chromosomal/ genetic abnormality
6. Placenta accreta spectrum disorder (accreta/ increta/ percreta)
7. Placenta covers the internal os by more than 2.5 centimeters (cm) at time of 2nd trimester anatomic ultrasound (18 0/7 and 20 6/7 weeks gestation)
8. The subject has experienced vaginal bleeding after 13 6/7 weeks gestation
9. One or more of the following uterine risk factors are present: fibroids \> 5.0cm, uterine malformation, history of classical cesarean section, history of prior uterine surgery with trans-myometrial penetration (excludes low transverse cesarean section)
10. The subject has a planned cesarean section or induction of labor prior to 370/7 weeks gestation
11. The subject had a cerclage or pessary placed prior to enrollment window in the current pregnancy
12. The subject has received enoxaparin, heparin, heparin sodium or other low molecular weight heparin since last menstrual period
13. Subject has current diagnosis of polyhydramnios
14. Subject has known use of illicit drugs in the current pregnancy, including cocaine, methamphetamine, and/or opioid use disorder in the current pregnancy
15. Subject is allergic to aspirin or has experienced gastrointestinal bleeding associated with use
16. Subject is allergic to peanuts and/or peanut oil used in exogenous progesterone formulation
17. Subject is participating in any other interventional research studies during the current pregnancy
18. Subject has tested positive for COVID-19 via an FDA-authorized diagnostic test for SARS-CoV-2 within the ten days prior to PreTRM® sample collection
19. Subject has been evaluated for COVID-19 salient symptoms per the American College of Obstetrics and Gynecology/ Society for Maternal Fetal Medicine (ACOG/SMFM) "Outpatient Assessment and Management for Pregnant Women with Suspected or Confirmed Novel Coronavirus (COVID-19)" in an emergency room (ER) or hospital setting since the last menstrual period (LMP) date.
20. Subject has a chronic medical disease(s) which require intensive medical surveillance and may increase the risk of preterm delivery to include:

    * Lupus
    * Chronic lung diseases on oxygen replacement
    * Cardiac disease with high risk of maternal mortality, including Marfan syndrome with dilated aortic root and significant pulmonary hypertension
    * Neuromuscular diseases at risk for pulmonary insufficiency (e.g. myotonic dystrophy)
    * Renal failure on dialysis
    * Uncontrolled or poorly controlled hyperthyroidism

Primary outcomes:
measure: Neonatal morbidity/mortality
timeFrame: Through initial neonate discharge from hospital after birth for all neonates, assessed up to 180 days.
measure: Length of neonatal hospital stay
timeFrame: Through initial neonate discharge from hospital after birth for all neonates, assessed up to 180 days.
Secondary outcomes:
measure: Length of NICU hospital stay for neonates reduction
timeFrame: Through initial neonate discharge from hospital after birth or until neonatal death, whichever occurs first, assessed up to 180 days.
measure: Increase gestation
timeFrame: Gestational age at delivery
Other outcomes:
measure: Reduction in occurrence of one or more major neonatal morbidities
timeFrame: 3 year infant follow-up
measure: Cost reduction of neonatal hospitalizations for all admissions
timeFrame: Birth up to neonatal discharge, assessed up to 180 days
measure: Cost reduction of neonatal hospitalizations for NICU admissions
timeFrame: Birth up to neonatal discharge, assessed up to 180 days
measure: Cost reduction of neonatal hospitalizations for PTB admissions
timeFrame: Birth up to neonatal discharge, assessed up to 180 days
measure: Cost reduction of neonatal hospitalizations for PTB admissions after sPTB
timeFrame: Birth up to neonatal discharge, assessed up to 180 days
measure: Reduction in rate of preterm birth <32 weeks gestation
timeFrame: Delivery
measure: Reduction in rate of preterm birth <35 weeks gestation
timeFrame: Delivery
measure: Reduction in rate of preterm birth <37 weeks gestation
timeFrame: Delivery
measure: Reduction in rate of preterm birth <32 weeks gestation after sPTB
timeFrame: Delivery
measure: Reduction in rate of preterm birth <35 weeks gestation after sPTB
timeFrame: Delivery
measure: Reduction in rate of preterm birth <37 weeks gestation after sPTB
timeFrame: Delivery
measure: NICU days reduction/NICU admissions <37 weeks
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: NICU days reduction/NICU admissions of sPTB neonates with NICU admission
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: NICU days reduction/NICU admissions of all preterm neonates
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: NICU days reduction/NICU admissions of sPTB neonates
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: Preterm neonatal hospital stay reduction
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: Preterm neonatal hospital stay reduction for sPTB
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, up to 180 days of life
measure: Neonatal hospital and NICU stay reduction after readmission for all admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Neonatal hospital and NICU stay reduction after readmission for NICU admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Neonatal hospital and NICU stay reduction after readmission for PTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Neonatal hospital and NICU stay reduction after readmission for sPTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Hospital readmission cost reduction for all admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Hospital readmission cost reduction for NICU admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Hospital readmission cost reduction for PTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Hospital readmission cost reduction for sPTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within 180 days of life for those discharged prior to 180 days of life
measure: Hospital readmission cost reduction for all admissions within first year of life
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first year of life
measure: Hospital readmission cost reduction within first year of life for NICU admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first year of life
measure: Hospital readmission cost reduction within first year of life for PTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first year of life
measure: Hospital readmission cost reduction within first year of life for sPTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first year of life
measure: Hospital readmission cost reduction within first three years of life for all admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first three years of life
measure: Hospital readmission cost reduction within first three years of life for NICU admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first three years of life
measure: Hospital readmission cost reduction within first three years of life for PTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first three years of life
measure: Hospital readmission cost reduction within first three years of life for sPTB admissions
timeFrame: From initial neonatal discharge to home (assessed up to 180 days of life) and within first three years of life
measure: NICU admission rate reduction
timeFrame: Through initial neonatal discharge from hospital after birth or until neonatal death, whichever occurs first, assessed up to 180 days
measure: Neonatal morbidity and mortality index observation
timeFrame: Within one year of primary analysis
measure: Neonatal hospital length of stay observation
timeFrame: Within one year of primary analysis
measure: NICU length of stay observation
timeFrame: Within one year of primary analysis
measure: Duration of gestation observation
timeFrame: Within one year of primary analysis
measure: Major neonatal morbidities observation
timeFrame: Within one year of primary analysis
measure: NICU length of stay amongst preterm neonates observation
timeFrame: Within one year of primary analysis
measure: Hospital length of stay amongst preterm neonates observation
timeFrame: Within one year of primary analysis
measure: Preterm birth rate observation
timeFrame: Within one year of primary analysis
measure: Neonatal hospitalization cost observation
timeFrame: Within one year of primary analysis
measure: Preterm neonatal hospitalization observation
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/neonatal morbidity and mortality index
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/length of neonatal hospital stay
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/length of NICU stay
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/duration of gestation
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/major neonatal morbidities
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/length of NICU stay amongst preterm neonates
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/length of hospital stay amongst preterm neonates
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/preterm birth rate
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/neonatal hospitalization
timeFrame: Within one year of primary analysis
measure: Intervention protocol observation/neonatal hospitalization amongst preterm neonates
timeFrame: Within one year of primary analysis
measure: COVID-19 primary
timeFrame: Within one year of primary analysis
measure: COVID-19 secondary
timeFrame: Within one year of primary analysis
measure: COVID-19 exploratory
timeFrame: Within one year of primary analysis
measure: Anxiety - Generalized Anxiety Disorder 7-item (GAD-7)
timeFrame: Within one year of primary analysis
measure: Anxiety - Perinatal Anxiety Screening Scale (PASS)
timeFrame: Within one year of primary analysis
Locations:
city: San Diego
country: United States
facility: UCSD
state: California
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: Newark
country: United States
facility: Delaware/Christiana Care
state: Delaware
city: Panama City
country: United States
facility: Emerald Coast
state: Florida
city: Lexington
country: United States
facility: University of Kentucky Healthcare
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner
state: Louisiana
city: Shreveport
country: United States
facility: LSU
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Las Vegas
country: United States
facility: High Risk Pregnancy Center
state: Nevada
city: New York
country: United States
facility: Mt Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Galveston
country: United States
facility: UTMB
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Health Care Services
state: Virginia
city: Richmond
country: United States
facility: VPFW
state: Virginia
city: Milwaukee
country: United States
facility: MCW
state: Wisconsin
Study officials:
affiliation: High Risk Pregnancy Center
name: Brian Iriye, MD
role: PRINCIPAL_INVESTIGATOR
References: