Acetylsalicylic Acid Discontinuation Between Weeks 24 and 26 for Prevention of Preterm Preeclampsia in Pregnant Women at High Risk

Primary objective: to determine whether discontinuation of acetylsalicylic acid between gestational weeks 24 and 26 is non‑inferior to continued administration until week 36 for the prevention of preterm preeclampsia, thereby informing optimal timing of therapy.

Secondary objectives:

• To assess whether stopping acetylsalicylic acid influences maternal, fetal, or neonatal morbidity and mortality.
• To evaluate the effect of discontinuation on the incidence of maternal bleeding.

The trial enrolled 5,000 adult women identified as high‑risk for preeclampsia based on a first‑trimester multiparametric screening performed between 11 + 0 and 13 + 6 weeks of gestation; all participants were over 18 years of age, had a singleton pregnancy, and were able to read and understand the informed consent. Selection required classification as high risk by the screening algorithm, voluntary consent, and willingness to adhere to the study protocol, which included aspirin administration, scheduled blood tests, and ultrasound examinations. No specific dietary, physical‑activity, or habit‑related restrictions were stipulated for the cohort. The population consisted exclusively of female subjects, reflecting the obstetric focus of the investigation.

The study is a phase III, low‑intervention, randomized, controlled trial evaluating whether discontinuation of oral acetylsalicylic acid 150 mg between gestational weeks 24 and 26 is non‑inferior to continuation until week 36 for preventing preeclampsia in high‑risk singleton pregnancies. Eligible participants are women ≥ 18 years who have undergone first‑trimester screening (11⁺0 to 13⁺6 weeks) and meet the high‑risk criteria, provide informed consent, and agree to study procedures. After a screening visit confirming eligibility, participants are randomized to either the discontinuation or continuation arm. Follow‑up visits are scheduled at weeks 24–26 (randomization), then approximately every four weeks until week 36, with each visit including safety assessments, blood tests, and ultrasound examinations. The end‑of‑study visit occurs at week 36 or at delivery, at which point primary and secondary outcomes are collected. Participant involvement spans from the screening visit in the first trimester through the final visit, lasting up to 24 weeks of treatment exposure. Early termination may occur if significant maternal hemorrhage, severe maternal, fetal, or neonatal morbidity or mortality arises, or if the participant withdraws consent.

The investigational product is acetylsalicylic acid administered orally at a dose of 150 mg. The pharmaceutical form is not specified in the source data. The medication is provided to participants for ingestion according to the study schedule.

In the control arm, participants receive the same oral aspirin preparation at 150 mg and continue the regimen until gestational week 36, serving as the comparator for the experimental strategy of discontinuation between weeks 24 and 26.

Dosing occurs once daily as per the protocol‑defined schedule, with the experimental group instructed to cease administration after week 24‑26 and the control group to maintain dosing through week 36. Participant adherence is monitored through scheduled study visits, pill counts, and participant diaries to ensure compliance with the assigned regimen.

The primary efficacy assessment will compare the incidence of preterm preeclampsia in participants who discontinue acetylsalicylic acid between weeks 24 and 26 with that in participants who continue therapy until week 36, using a predefined non‑inferiority margin.

Secondary efficacy evaluations will examine whether discontinuation affects maternal, fetal, or neonatal morbidity or mortality and will assess the risk of maternal hemorrhage.