Low Dose Aspirin for Prevention of Early Pregnancy Loss

Low Dose Aspirin for Prevention of Early Pregnancy Loss in Women at High Risk of Preeclampsia

Preeclampsia is a pregnancy-specific, multisystem disorder affecting 3% to 8% of pregnancies and remains a significant cause of maternal and neonatal morbidity and mortality worldwide.

The World Health Organization estimates that approximately 76,000 maternal deaths annually are attributed to preeclampsia, accounting for 16% of global maternal mortality, with the majority occurring in low- and middle-income countries

Study Overview

• Status: Recruiting
• Conditions: Pre-Eclampsia
• Intervention / Treatment: Drug: Aspirin

Detailed Description

The pathogenesis of preeclampsia (PE) is not fully understood, but it is believed to be associated with impaired early placental development, primarily attributed to defective trophoblast invasion and remodeling of the spiral arterioles .

Various mechanisms have been proposed to contribute to the development of preeclampsia, including angiogenesis, endothelial injury, oxidative stress, and inflammation, which lead to clinical manifestations such as hypertension, proteinuria, and end organ damage .

Preeclampsia is associated with severe short- and long-term maternal and neonatal morbidities, and its occurrence is influenced by risk factors such as diabetes, hypertension, multifetal gestation, as well as the severity and timing of previous preeclampsia episodes .

While low-dose aspirin (LDA) has shown some benefit in preventing preeclampsia and fetal growth restriction when initiated before 16 weeks' gestation, there is no widely effective prophylactic therapy, and delivery remains the primary approach to prevent maternal morbidity and mortality.

Recent research has indicated that LDA intervention, following firsttrimester screening of women at risk of developing preeclampsia, can significantly reduce the occurrence of preterm PE .

As such, LDA's use is increasingly considered standard practice for women at high risk of developing preeclampsia .

Nevertheless, the potential role of low-dose aspirin in preventing early pregnancy loss in this specific high-risk population remains underexplored. Given that abnormal placentation and inflammation are associated with both early and late pregnancy losses, low-dose aspirin therapy has the potential to mitigate these complications.

However, current evidence on aspirin's efficacy in preventing early pregnancy loss is limited. Considering this, we propose a randomized, double-blind, placebocontrolled trial to investigate whether low-dose aspirin (81 mg daily) administered before 16 weeks of gestation can effectively reduce the rate of early pregnancy loss in women at high risk of developing preeclampsia.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hany Hosny, Resident; Phone Number: 01274580828; Email: hanyhosny123@yahoo.com

Study Locations

• Egypt
  • Assuit
    • Asyūţ, Assuit, Egypt
      • Recruiting
      • Assuit University hospitals
      • Contact: Mohamed Nagy, Lecturer; Phone Number: 01096655458; Email: drmnagy@aun.edu.eg
      • Principal Investigator: Abdelrahman Mahmoud, Assist.Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Singleton pregnancy
• Before 8 weeks gestation
• Women at high risk of preeclampsia according to Royal College of Obstetricians and Gynecologists (RCOG) (Robson et al., 2013):
• Maternal age ≥ 35 years.
• Nulliparity.
• BMI ≥ 30 kg/m2.
• Smoking of r ≥ 10 cigarettes per day.
• Previous history of small for gestational age (SGA) baby.
• Previous history of stillbirth.
• Pregnancy interval < 6 months or ≥ 60months.
• Chronic hypertension.
• Diabetes with vascular disease.
• Willingness to participate in the study and provide informed written consent.

Exclusion Criteria:

• Known allergy or hypersensitivity to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Use of any anticoagulant medication (e.g., heparin, warfarin, clopidogrel)
• Use of low-dose aspirin for any indication prior to the current pregnancy
• Chronic use of NSAIDs or corticosteroids
• History of bleeding disorder or active bleeding
• Any medical condition that may contraindicate the use of low-dose aspirin (e.g., peptic ulcer disease, asthma, liver, or kidney disease)
• Multiple gestation
• Inability to provide informed consent or comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (Experimental Group); About 125 Participants in the treatment group will receive 81 mg low-dose aspirin once daily starting from the time of enrollment and continuing until the end of pregnancy	Drug: Aspirin; To investigate the efficacy of low dose aspirin for prevention of early pregnancy loss in women at high risk of preeclampsia.; Other Names: Low Dose Asprin
Placebo Comparator: Group B (Control Group); About 125 Participants will receive only the routine care of pregnancy until the end of pregnancy	Drug: Aspirin; To investigate the efficacy of low dose aspirin for prevention of early pregnancy loss in women at high risk of preeclampsia.; Other Names: Low Dose Asprin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of pregnancy loss	To investigate the efficacy of low dose aspirin (81 mg) for prevention of early pregnancy loss in women at high risk of preeclampsia.	From base line to the end of pregnancy

Collaborators and Investigators

• Sponsor: Egymedicalpedia
• Investigators: Study Chair: Mohamad Sayed, Professor, Assiut University, Faculty of medicine, Assuit.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 15, 2025

Study Registration Dates

• First Submitted: February 7, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Estimated): February 15, 2024

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Eclampsia; Pre-Eclampsia; Abortion, Spontaneous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: Hany Hosny

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No