Aspirin for the Prevention of Preeclampsia and Pregnancy outcomes in nulliparous women after Assisted Reproductive Technology. APPART trial

The primary objective of this study is to evaluate the effect of **aspirin** 150mg daily, initiated between 9 and 14 weeks of gestation, versus placebo in the prevention of preterm preeclampsia (<37 weeks of gestation) in nulliparous pregnant women after assisted reproductive technology. This is clinically relevant as preeclampsia is a significant cause of maternal and neonatal morbidity and mortality, and early intervention could potentially improve pregnancy outcomes.

Secondary objectives include:

• Comparing the effect of aspirin on spontaneous and total preterm birth <34 weeks and <37 weeks of gestation.
• Assessing the impact on the occurrence of preeclampsia <34 weeks and term preeclampsia (≥37 weeks of gestation).
• Evaluating the effect on cesarean delivery, postpartum hemorrhage (>500ml), and placental abruption.
• Investigating the occurrence of severe maternal morbidity and neonatal adverse outcomes, including stillbirth, neonatal death, and complications.
• Comparing birthweight outcomes and assessing the overall safety of aspirin in the specified population.
• Documenting adherence to treatment and assessing the cost of care and efficiency through cost-effectiveness analysis.
• Evaluating the impact of socioeconomic characteristics on the cost of care and efficiency.

The clinical trial focuses on **preeclampsia during pregnancy** and involves a study population of nulliparous women aged 18 years or older. Participants are exclusively female, as the trial is centered on pregnancy-related conditions. The trial targets women who have achieved pregnancy through assisted reproductive technology (ART), including methods such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), oocyte donation, or intrauterine insemination with a sperm donor. The study is limited to those with a singleton, evolutive pregnancy between 9 and 14 weeks of gestation. Participants must be affiliated with French Social Security Insurance or an equivalent social protection system and have provided written informed consent. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on these specific criteria to ensure a focused investigation into the prevention of preterm preeclampsia in this particular demographic.

The clinical trial is designed to evaluate the effect of **acetylsalicylic acid** (aspirin) at a dosage of 150 mg daily, initiated between 9 and 14 weeks of gestation, compared to a placebo, in preventing preterm preeclampsia in nulliparous pregnant women following assisted reproductive technology. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to run until December 31, 2026, with recruitment having commenced on January 2, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being nulliparous, aged 18 or older, having a singleton pregnancy following assisted reproductive technology, and being between 9 and 14 weeks of gestation. Follow-up visits will be scheduled to monitor adherence to the treatment, assess any adverse events, and collect data on primary and secondary endpoints, including the occurrence of preterm preeclampsia and other pregnancy-related outcomes. The end-of-study visit will occur after delivery, where final assessments will be conducted, and data on maternal and neonatal outcomes will be collected.

The expected length of participant involvement is approximately 26 weeks, corresponding to the maximum treatment period with the study drug. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or the occurrence of serious adverse events that necessitate discontinuation of the study drug. The trial aims to provide valuable insights into the cost-effectiveness and impact of aspirin in preventing preeclampsia, with socioeconomic factors also being evaluated to understand their influence on healthcare costs and outcomes.

The clinical trial involves the administration of **acetylsalicylic acid** as the experimental medication. This compound, commonly known as aspirin, is provided in a **hard capsule** form. The dosage is set at 150 mg per day, administered **orally**. The treatment is initiated between 9 and 14 weeks of gestation and continues for a maximum period of 26 weeks. The primary objective of this regimen is the **preventive treatment for preterm preeclampsia** in nulliparous pregnant women who have undergone assisted reproductive technology. The compliance of participants with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The study also includes a **placebo** group, which receives microcrystalline cellulose capsules. These capsules are designed to match the size and color of the active drug capsules, ensuring blinding of the study. The placebo is administered with the same frequency and route as the active treatment, maintaining consistency in the administration process. This comparator treatment serves to evaluate the efficacy of acetylsalicylic acid by providing a baseline for comparison against the experimental group.

The efficacy of acetylsalicylic acid in the prevention of preterm preeclampsia will be assessed in a clinical trial involving nulliparous pregnant women who have undergone assisted reproductive technology. The primary endpoint for evaluating efficacy is the occurrence of preterm preeclampsia, defined as delivery before 37 weeks of gestation, measured as a binary variable (yes/no). Secondary endpoints include the occurrence of spontaneous and total preterm birth at less than 34 and 37 weeks of gestation, term preeclampsia, preeclampsia before 34 weeks, cesarean delivery, postpartum hemorrhage, placental abruption, stillbirth, birthweight, and severe maternal morbidity. Additional secondary endpoints involve neonatal outcomes such as neonatal death or complications, maternal adverse events, treatment adherence, resource consumption, and cost-effectiveness analysis.

Efficacy parameters will be collected and analyzed throughout the trial, with specific timepoints for assessment not explicitly detailed. The trial will utilize a placebo-controlled design, with participants receiving either 150 mg of acetylsalicylic acid or a placebo daily, initiated between 9 and 14 weeks of gestation. Adherence to the treatment will be monitored by counting pills at each visit and using a diary or application. The trial is expected to conclude by December 31, 2026, with recruitment having started on January 2, 2023.