Aspirin Dose Escalation for the Prevention of Recurrent Preterm Delivery Trial

NCT ID: NCT06980025

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-10

Study Completion Date

2029-02-28

Brief Summary

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This is a phase-III multi-center double-blind randomized clinical trial of 1,800 individuals with a history of prior preterm birth at less than 35 weeks gestation who are randomized to either 162 mg aspirin or 81 mg aspirin daily. The study drug will be initiated between 10 and 15 weeks gestation and continued through 36 weeks, 6 days gestation. The primary endpoint is recurrent preterm delivery or fetal death prior to 35 weeks, 0 days gestation.

Detailed Description

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This is a phase-III multi-center double-blind randomized clinical trial of 1,800 individuals with a history of prior preterm birth at less than 35 weeks gestation who are randomized to either 162 mg aspirin or 81 mg aspirin daily.

The primary objective is to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing recurrent preterm delivery or fetal death before 35 weeks, 0 days gestation in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with spontaneous preterm delivery (sPTB), ischemic placental disease (IPD), or stillbirth. Ischemic placental disease includes small for gestational age, preeclampsia, or placental abruption.

The secondary objective is to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing ischemic placental disease in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with sPTB, IPD, or stillbirth.

Tertiary /Exploratory objectives are 1) to assess the efficacy of daily 162 mg of aspirin compared to 81 mg aspirin in reducing adverse maternal and neonatal outcomes, and 2) to assess maternal and neonatal safety in individuals with a proximal birth between 20 weeks, 0 days and 34 weeks, 6 days gestation with sPTB, IPD, or stillbirth.

Individuals will be randomized between 10 and 15 weeks gestation to either 162mg or 81mg of aspirin daily and continue the study intervention through 36 weeks, 6 days gestation. Participants will have monthly virtual or in-person visits through 37 weeks gestation to assess study intervention compliance, side effects, medication use, and unscheduled hospitalization. Maternal blood will be collected in a subset of the population. Research staff will abstract maternal and neonatal outcomes following delivery and discharge from the hospital.

Conditions

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Preterm Delivery Obstetrical Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Individuals will be randomized between 10 weeks, 0 days gestation and 15 weeks, 6 days gestation to either aspirin 162 mg or aspirin 81 mg daily and continue the study intervention through 36 weeks, 6 days gestation. Randomization will be stratified by clinical site.
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The study intervention is packaged and shipped from the central distribution center to the clinical sites. Participants, clinical staff, and clinical site investigators and research staff are masked to the study intervention.

Study Groups

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162mg Aspirin Daily

One 81mg capsule of aspirin daily through 36 weeks 6 days gestation.

Group Type EXPERIMENTAL

162mg Aspirin

Intervention Type DRUG

Two 81mg aspirin tablets in an over-encapsulated capsule filled with microcrystalline cellulose.

Study intervention will be packaged into bottles (35 capsules per bottle).

81mg Aspirin Daily

Two 81mg capsules of aspirin daily through 36 weeks 6 days gestation.

Group Type EXPERIMENTAL

81mg Aspirin

Intervention Type DRUG

One 81mg aspirin tablet in an over-encapsulated capsule filled with microcrystalline cellulose.

Study intervention will be packaged into bottles (35 capsules per bottle).

Interventions

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162mg Aspirin

Two 81mg aspirin tablets in an over-encapsulated capsule filled with microcrystalline cellulose.

Study intervention will be packaged into bottles (35 capsules per bottle).

Intervention Type DRUG

81mg Aspirin

One 81mg aspirin tablet in an over-encapsulated capsule filled with microcrystalline cellulose.

Study intervention will be packaged into bottles (35 capsules per bottle).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 14 years or older
* Singleton gestation. Twin gestation reduced to a singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher-order multifetal gestations reduced to singletons are not eligible.
* Gestational age at randomization between 10 weeks 0 days and 15 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
* Prior preterm birth between 20 weeks 0 days and 34 weeks 6 days with one of the following in the proximal birth reaching 20 weeks or greater:

* Spontaneous preterm birth is defined as spontaneous preterm labor or premature rupture of membranes
* Ischemic placental disease is defined as preeclampsia, small for gestational age, fetal growth restriction, or placental abruption, as defined clinically.
* Stillbirth excluding those with known genetic disorders or major congenital anomalies.

Exclusion Criteria

* Known allergy or hypersensitivity to aspirin or any medical condition where aspirin is contraindicated (e.g., history of peptic ulcer disease, nasal polyps, NSAID-induced asthma, history of gastrointestinal bleeding, known G6PD deficiency, severe hepatic dysfunction, bleeding disorders, and consumption of 3 or more alcoholic drinks per day)
* Taking other anticoagulants such as Heparin or Low-Molecular weight Heparin
* Thrombocytopenia defined as a platelet count defined as a platelet count \<100,000 microliters
* Gastric bypass surgery, regardless of type
* Aspirin use \>81 mg daily during the current pregnancy who are not willing or able to go through a 2-week washout before randomization.
* Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery.
* Known fetal genetic disease or major malformations
* Fetal demise or planned termination of pregnancy. Selective reduction by 13 weeks 6 days gestation, from twins to singleton, is not an exclusion.
* Any fetal/maternal condition requiring invasive in-utero assessment or treatment, for example, significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia.
* Patients with any of the following medical conditions because of increased risk for adverse pregnancy outcome or indicated preterm birth:

* Treated hypertension requiring more than one agent
* Chronic renal disease with baseline serum creatinine ≥1.5 mg/dL
* Conditions treated with chronic oral glucocorticoid therapy (e.g., systemic lupus erythematosus)
* Uncontrolled hyper- and hypothyroid disease
* New York Heart Association (NYHA) stage II or greater cardiac disease
* Planned indicated delivery prior to 37 weeks.
* Participation in another interventional study that influences the primary outcome in this study (gestational age at delivery).
* Participation in this trial in a previous pregnancy.
* Delivery planned at a non-participating site
Minimum Eligible Age

14 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Columbia University

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rebecca G Clifton, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Washington University Biostatistics Center

Matthew K Hoffman, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

ChristianaCare Center for Women & Children's Health Research

Uma M Reddy, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Cande Ananth, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

Robert Wood Johnson Medical School - Rutgers Health

Locations

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University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Regents of the University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

Case Western Reserve University

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Brown University

Providence, Rhode Island, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

University of Texas - Houston

Houston, Texas, United States

Site Status RECRUITING

University of Utah Medical Center

Salt Lake City, Utah, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rebecca G Clifton, PhD

Role: CONTACT

301-881-9260

Trisha Boekhoudt, MPH

Role: CONTACT

Facility Contacts

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Nancy Saxon, RN, BSN

Role: primary

205-934-1616

Natalie Oman, MPH

Role: primary

206-718-4703

Elizabeth Rangel, RN

Role: primary

Megan Loffredo, MD, CCRC

Role: primary

203-722-1058

Kelly Clark, RN

Role: primary

919-350-6117

Jennifer Ferrara, RNC MSN

Role: primary

919-681-6176

Abigail Pierse, BS

Role: primary

216-778-8443

Anna Bartholomew, RN, BSN

Role: primary

614-685-3229

Christina Pizzi, RN

Role: primary

267-273-8574

Jeanette Boyce, RN

Role: primary

412-527-8118

Angelica DeMartino, RN, BSN

Role: primary

401-274-1122 ext. 48521

Christina Reed, RN, NP

Role: primary

832-826-7377

Jia Chen, RN, CCRP

Role: backup

713-798-3798

Felecia Ortiz, RN

Role: primary

713-500-6467

Amber Sowles, RN BSN

Role: primary

801-585-5499

Other Identifiers

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U01HD109332

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U24HD036801

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD1036801-ADEPT

Identifier Type: -

Identifier Source: org_study_id

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