Clinical trial NCT05924971: Aspirin for Postpartum Patients With Preeclampsia
Official title: Acetylsalicylic Acid for Postpartum Preeclampsia: A Pilot Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Preeclampsia Postpartum
Keywords: Preeclampsia
Postpartum
Aspirin
sFlt-1
Lead sponsor: MemorialCare Health System
Sponsor class: OTHER
Collaborators: name: University of California, Irvine
First posted: 2023-06-29
Enrollment: 86
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with preeclampsia will be randomized after delivery to receive either standard blood pressure control plus aspirin 81 mg or standard blood pressure control alone.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Reduction in sFlt-1
timeFrame: 1 week postpartum
Secondary outcomes:
measure: Normotension (ACOG)
timeFrame: 1 week postpartum
measure: Normotension (JNC)
timeFrame: 1 week postpartum
measure: Time to normotension
timeFrame: 6 weeks postpartum
measure: Anti-hypertensive therapy
timeFrame: 6 weeks postpartum
measure: Readmission
timeFrame: 6 weeks postpartum
measure: Adherence
timeFrame: 1 week postpartum
measure: Enrollment feasibility
timeFrame: 1 week postpartum
measure: Postpartum hemorrhage
timeFrame: 6 weeks postpartum
measure: Postpartum bleeding requiring intervention
timeFrame: 6 weeks postpartum
measure: Unplanned postpartum evaluation for bleeding
timeFrame: 6 weeks postpartum
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital, Long Beach/MemorialCare Long Beach
state: California
Study officials:
affiliation: Miller Children's and Women's Hospital, Long Beach/ MemorialCare Medical Center
name: Megan C Oakes, MD MSCI
role: PRINCIPAL_INVESTIGATOR
References:
citation: ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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 Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-1324. doi: 10.1161/HYP.0000000000000066. Epub 2017 Nov 13. No abstract available.