Aspirin for Postpartum Patients With Preeclampsia

Официальное название

Acetylsalicylic Acid for Postpartum Preeclampsia: A Pilot Randomized Trial

Обзор

The purpose of this research study is to evaluate the effect of low-dose aspirin on recovery from severe preeclampsia (a high blood pressure disorder of pregnancy) among women who have given birth. We hypothesize that taking aspirin for the first week after giving birth will enhance recovery from preeclampsia by decreasing the levels of a protein called soluble fms-like tyrosine kinase (sFlt-1), which is thought to be a main contributor to the development of preeclampsia, and speeding up return to a normal blood pressure.

Подробное описание

Preeclampsia is a condition of the antenatal and postpartum periods, which manifests as new-onset hypertension and end-organ damage. Globally, preeclampsia is estimated to affect up to 9% of all pregnancies, though as many as two-thirds of patients who receive this diagnosis will remain hypertensive beyond the time of their postpartum hospital discharge. Because of this, postpartum preeclampsia is the leading cause of postpartum hospital readmission in the United States. Anti-hypertensive medications and magnesium sulfate are temporizing therapies aimed at preventing the immediate sequelae of preeclampsia such as seizures, stroke, and end-organ damage. However, there are no therapies directly targeting the pathophysiology underlying postpartum preeclampsia, which poses difficulties in promoting blood pressure recovery to a normotensive state.

Preeclampsia is considered a disorder of abnormal placentation, leading to the release of abnormal pro-angiogenic, anti-angiogenic, and vasoactive molecules. Specifically, excess elevations in anti-angiogenic proteins like soluble fms-like tyrosine kinase 1 (sFlt-1) relative to pro-angiogenic proteins like placental growth factor (PlGF) are thought to cause vasospasm and, in turn, hypertension. As such, it seems plausible that persistent postpartum sFlt-1 elevation is implicated in the pathophysiology of postpartum preeclampsia.

At low doses, acetylsalicylic acid, or aspirin, has been proven to target the aforementioned angiogenic imbalance by decreasing serum sFlt-1 levels. While aspirin is widely used during pregnancy to mitigate the risk of preeclampsia, the utility of aspirin in the postpartum period to target these pathways and promote BP recovery to a normotensive state is unknown. The central hypothesis of this trial is that use of aspirin in the first week postpartum will enhance recovery from preeclampsia by improving blood pressure recovery via decreased levels of sFlt-1.

Вмешательства

• Препарат Aspirin 81Mg Ec Tab
  Aspirin 81 mg 1 tablet by mouth. Participants randomized to receive aspirin in addition to standard blood pressure management will receive the study medication nightly at 20:00, with first dose initiated within 24 hours of delivery.

Первичные конечные точки

• Reduction in sFlt-1 [Срок оценки: 1 week postpartum]

Вторичные конечные точки (10)

• Normotension (ACOG) [Срок оценки: 1 week postpartum]
• Normotension (JNC) [Срок оценки: 1 week postpartum]
• Time to normotension [Срок оценки: 6 weeks postpartum]
• Anti-hypertensive therapy [Срок оценки: 6 weeks postpartum]
• Readmission [Срок оценки: 6 weeks postpartum]
• Adherence [Срок оценки: 1 week postpartum]
• Enrollment feasibility [Срок оценки: 1 week postpartum]
• Postpartum hemorrhage [Срок оценки: 6 weeks postpartum]
• Postpartum bleeding requiring intervention [Срок оценки: 6 weeks postpartum]
• Unplanned postpartum evaluation for bleeding [Срок оценки: 6 weeks postpartum]

Критерии участия

Критерии включения

• Preeclampsia with severe features diagnosed during delivery admission, as defined by ACOG criteria.
• Pre- and postnatal care provided by the Long Beach Memorial Ob/Gyn resident or Maternal-Fetal Medicine clinic.

Критерии исключения

• Patient age <18 years old
• Non-English or Non-Spanish speaking
• Chronic hypertension diagnosed before 20 weeks' gestation
• Known allergy, prior adverse reaction, or any medical condition in which aspirin is contraindicated (nasal polyps, gastric or duodenal ulcers, history of gastrointestinal bleeding, severe hepatic dysfunction)
• Aspirin prescribed postpartum for any other medical condition
• Bleeding disorder
• Breastfeeding an infant with thrombocytopenia

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Miller Children's and Women's Hospital, Long Beach/MemorialCare Long Beach — Long Beach

Публикации

• ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018. PMID 30575675
• Ditisheim A, Wuerzner G, Ponte B, Vial Y, Irion O, Burnier M, Boulvain M, Pechere-Bertschi A. Prevalence of Hypertensive Phenotypes After Preeclampsia: A Prospective Cohort Study. Hypertension. 2018 Jan;71(1):103-109. doi: 10.1161/HYPERTENSIONAHA.117.09799. Epub 2017 Nov 13. PMID 29133363
• Mogos MF, Salemi JL, Spooner KK, McFarlin BL, Salihu HH. Hypertensive disorders of pregnancy and postpartum readmission in the United States: national surveillance of the revolving door. J Hypertens. 2018 Mar;36(3):608-618. doi: 10.1097/HJH.0000000000001594. PMID 29045342
• Agrawal S, Cerdeira AS, Redman C, Vatish M. Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia: The SaPPPhirE Study. Hypertension. 2018 Feb;71(2):306-316. doi: 10.1161/HYPERTENSIONAHA.117.10182. Epub 2017 Dec 11. PMID 29229743
• Su MT, Wang CY, Tsai PY, Chen TY, Tsai HL, Kuo PL. Aspirin enhances trophoblast invasion and represses soluble fms-like tyrosine kinase 1 production: a putative mechanism for preventing preeclampsia. J Hypertens. 2019 Dec;37(12):2461-2469. doi: 10.1097/HJH.0000000000002185. PMID 31335509
• Lin L, Li G, Zhang W, Wang YL, Yang H. Low-dose aspirin reduces hypoxia-induced sFlt1 release via the JNK/AP-1 pathway in human trophoblast and endothelial cells. J Cell Physiol. 2019 Aug;234(10):18928-18941. doi: 10.1002/jcp.28533. Epub 2019 Apr 19. PMID 31004367
• Neuman RI, Figaroa AMJ, Nieboer D, Saleh L, Verdonk K, Danser AHJ, Duvekot HJJ, van den Meiracker AH, Roeters van Lennep J, Visser W. Angiogenic markers during preeclampsia: Are they associated with hypertension 1 year postpartum? Pregnancy Hypertens. 2021 Mar;23:116-122. doi: 10.1016/j.preghy.2020.11.011. Epub 2020 Dec 3. PMID 33321329
• Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High PMID 29133354

Идентификаторы

NCT: NCT05924971 · 371-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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