Low Doses of Aspirin in the Prevention of Preeclampsia

NCT04070573 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 19-05020160
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

Brief Summary

Preeclampsia (PE) is a morbid and potentially lethal complication of pregnancy and is more common in women with specific risk factors. Aspirin (ASA) is currently the only prophylactic therapy for preeclampsia in high-risk women to be recognized by the US Preventive Task Force and should be initiated early in the second trimester of pregnancy, before 16 weeks of gestation. However, currently there is no literature comparing various low-dose ASA formulations in the risk reduction of PE. In the United States, the currently available low-dose ASA is over the counter and is found in 81mg tablets. Therefore, when clinicians initiate therapy with low dose ASA, they may prescribe 1 or 2 tablets of 81mg aspirin per day depending on personal preference and cannot be assisted by evidence to guide their decision.This study aims to determine the incidence of preterm PE or PE with severe features in women taking either 81mg or 162mg in a randomized setting, from a single center. The investigators hypothesize that the information gained from this trial will permit a more accurate sample size calculation for a larger clinical trial powered to accept or reject our testing hypothesis. If our hypothesis is rejected and 162mg of daily ASA is not associated with a lower incidence of severe or preterm PE compared to 81mg, this may be due to lack of power to detect a smaller effect. The investigators would then evaluate the feasibility and results and determine whether a larger trial is reasonable.

Conditions

Preeclampsia

Keywords

Preterm preeclampsia; Preeclampsia with severe features; High risk pregnancy; Low dose aspirin; Cell free RNA; Compliance

Outcome Measures

Primary Outcomes (3)

• Incidence of Preterm (<37 Weeks) Preeclampsia

  The incidence of preterm (\<37 weeks) preeclampsia in high risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.

  9 months for each patient (from recruitment until 6 weeks postpartum)

• Incidence of Preeclampsia With Severe Features

  The incidence of preeclampsia with severe features (American College of Obstetricians and Gynecologists 2019 definition) in high-risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.

  9 months for each patient (from recruitment until 6 weeks postpartum)

• Composite Primary Outcome

  Composite of preterm preeclampsia and/or preeclampsia with severe features

  9 months for each participant

Secondary Outcomes (4)

• Aspirin Adherence

  9 months for each patient (from recruitment until 6 weeks postpartum)

• Maternal and Fetal Outcomes

  9 months for each patient (from recruitment until 6 weeks postpartum)

• Time-to-event for Preeclampsia: Gestational Age at Onset of Preeclampsia

  9 months for each patient (from recruitment until 6 weeks postpartum)

• Aspirin Adherence- All Time Points Together

  9 months for each patient (from recruitment until 6 weeks postpartum)

Other Outcomes (1)

• Impact of Co-morbidities on Incidence of Preeclampsia

  9 months for each patient (from recruitment until 6 weeks postpartum)

Study Arms (2)

81mg ASA

ACTIVE COMPARATOR

Patients in Arm 1, will be instructed to take one tablet of 81mg aspirin per day.

Drug: acetylsalicylic acid

162mg ASA

ACTIVE COMPARATOR

Patients in Arm 2, will be instructed to take two tablets simultaneously orally once per day.

Drug: acetylsalicylic acid

Interventions

acetylsalicylic acid DRUG

High risk pregnant women will be treated with daily aspirin during pregnancy.

Also known as: aspirin, ASA

162mg ASA; 81mg ASA

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant patients, ≥18 years old, at less than 16 weeks' gestation (as documented by ultrasound) with at least one of the following risk factors for developing PE:
• PE in a prior pregnancy
• Chronic hypertension (prior to pregnancy or before 20 weeks' gestation)
• Type 1 or 2 diabetes
• Renal disease (proteinuria ≥300mg/day or estimated GFR\<90mL/min/1.73 m2)
• Multifetal gestation
• Autoimmune disease (e.g. systemic lupus erythematous, antiphospholipid syndrome)

You may not qualify if:

• Patient with known intention to terminate pregnancy
• Major fetal malformation seen on ultrasound
• Contraindication to ASA therapy (including but not limited to allergy and high bleeding risk)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (2)

New York Presbyterian - Weill Cornell

New York, New York, 10065, United States

Location

New York Presbyterian Queens

New York, New York, 11355, United States

Location

Related Publications (18)

• ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018.

  PMID: 30575675 BACKGROUND

• Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013 Dec;209(6):544.e1-544.e12. doi: 10.1016/j.ajog.2013.08.019. Epub 2013 Aug 22.

  PMID: 23973398 BACKGROUND

• Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659. doi: 10.1002/14651858.CD004659.pub2.

  PMID: 17443552 BACKGROUND

• Henderson JT, Whitlock EP, O'Conner E, Senger CA, Thompson JH, Rowland MG. Low-Dose Aspirin for the Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Apr. Report No.: 14-05207-EF-1. Available from http://www.ncbi.nlm.nih.gov/books/NBK196392/

  PMID: 24783270 BACKGROUND

• Abheiden CN, van Reuler AV, Fuijkschot WW, de Vries JI, Thijs A, de Boer MA. Aspirin adherence during high-risk pregnancies, a questionnaire study. Pregnancy Hypertens. 2016 Oct;6(4):350-355. doi: 10.1016/j.preghy.2016.08.232. Epub 2016 Aug 6.

  PMID: 27939481 BACKGROUND

• Wright D, Poon LC, Rolnik DL, Syngelaki A, Delgado JL, Vojtassakova D, de Alvarado M, Kapeti E, Rehal A, Pazos A, Carbone IF, Dutemeyer V, Plasencia W, Papantoniou N, Nicolaides KH. Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia. Am J Obstet Gynecol. 2017 Dec;217(6):685.e1-685.e5. doi: 10.1016/j.ajog.2017.08.110. Epub 2017 Sep 6.

  PMID: 28888591 BACKGROUND

• Shanmugalingam R, Hennessy A, Makris A. Aspirin in the prevention of preeclampsia: the conundrum of how, who and when. J Hum Hypertens. 2019 Jan;33(1):1-9. doi: 10.1038/s41371-018-0113-7. Epub 2018 Sep 19.

  PMID: 30232399 BACKGROUND

• Ngo TTM, Moufarrej MN, Rasmussen MH, Camunas-Soler J, Pan W, Okamoto J, Neff NF, Liu K, Wong RJ, Downes K, Tibshirani R, Shaw GM, Skotte L, Stevenson DK, Biggio JR, Elovitz MA, Melbye M, Quake SR. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science. 2018 Jun 8;360(6393):1133-1136. doi: 10.1126/science.aar3819.

  PMID: 29880692 BACKGROUND

• Koh W, Pan W, Gawad C, Fan HC, Kerchner GA, Wyss-Coray T, Blumenfeld YJ, El-Sayed YY, Quake SR. Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7361-6. doi: 10.1073/pnas.1405528111. Epub 2014 May 5.

  PMID: 24799715 BACKGROUND

• Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017 Feb;216(2):110-120.e6. doi: 10.1016/j.ajog.2016.09.076. Epub 2016 Sep 15.

  PMID: 27640943 BACKGROUND

• Seidler AL, Askie L, Ray JG. Optimal aspirin dosing for preeclampsia prevention. Am J Obstet Gynecol. 2018 Jul;219(1):117-118. doi: 10.1016/j.ajog.2018.03.018. Epub 2018 Mar 26. No abstract available.

  PMID: 29588190 BACKGROUND

• Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.

  PMID: 28657417 BACKGROUND

• Perneby C, Vahter M, Akesson A, Bremme K, Hjemdahl P. Thromboxane metabolite excretion during pregnancy--influence of preeclampsia and aspirin treatment. Thromb Res. 2011 Jun;127(6):605-6. doi: 10.1016/j.thromres.2011.01.005. Epub 2011 Feb 12. No abstract available.

  PMID: 21316743 BACKGROUND

• Vainio M, Riutta A, Koivisto AM, Maenpaa J. Prostacyclin, thromboxane A and the effect of low-dose ASA in pregnancies at high risk for hypertensive disorders. Acta Obstet Gynecol Scand. 2004 Dec;83(12):1119-23. doi: 10.1111/j.0001-6349.2004.00396.x.

  PMID: 15548142 BACKGROUND

• American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy. Obstet Gynecol. 2019 Jan;133(1):e26-e50. doi: 10.1097/AOG.0000000000003020.

  PMID: 30575676 BACKGROUND

• Perni U, Sison C, Sharma V, Helseth G, Hawfield A, Suthanthiran M, August P. Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy. Hypertension. 2012 Mar;59(3):740-6. doi: 10.1161/HYPERTENSIONAHA.111.181735. Epub 2012 Feb 6.

  PMID: 22311907 BACKGROUND

• Khander A, Thomas C, Matthews K, Christos P, Alcus C, Alam T, Bush L, Deshmukh D, Chasen ST, Riley LE, Skupski DW, August P, Malha L. Comparison of 162 mg and 81 mg Aspirin for Prevention of Preeclampsia: A Randomized Controlled Trial. Obstet Gynecol. 2026 Jan 1;147(1):87-96. doi: 10.1097/AOG.0000000000006100. Epub 2025 Oct 24.

  PMID: 41296512 DERIVED

• Khander A, Matthews K, Christos P, Thomas C, Alam T, Alcus C, Bush L, Edusei E, August P, Malha L. Randomised controlled trial comparing low doses of aspirin in the prevention of pre-eclampsia (ASAPP): a study protocol. BMJ Open. 2025 Jul 8;15(7):e096779. doi: 10.1136/bmjopen-2024-096779.

  PMID: 40633954 DERIVED

MeSH Terms

Conditions

Pre-Eclampsia; Patient Compliance

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr Line Malha
• Organization: Weill Cornell Medicine

lim9120@med.cornell.edu

6469622606

Study Officials

• Line Malha, MD, MS

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is an open label randomized controlled trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm 1: 81mg oral ASA daily. Arm 2: 162mg oral ASA daily. Patients will obtain their prescriptions from their respective pharmacies. Women in Arm 1, will be instructed to take one table of 81mg aspirin per day; those in Arm 2, will be asked to take two tablets simultaneously orally once per day. Therapy will be initiated at the baseline visit and continued until 1 week before planned delivery or upon admission for unplanned/imminent delivery as per clinical routine.

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: October 21, 2019
• Primary Completion: March 4, 2024
• Study Completion: January 23, 2025
• Last Updated: March 13, 2025
• Results First Posted: March 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)