SARS-CoV-2 and Acetylsalicylic Acid (SARA) (SARA)

Efficacy of Low Dose Acetylsalicylic Acid in Preventing Adverse Maternal and Perinatal Outcomes in SARS-CoV-2 Infected Pregnant Women

SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse maternal and perinatal outcomes. One explanation is that the infection might increase the existing pregnancy-associated prothrombotic status, leading to a higher risk of placental and vascular complications. Administration of low-dose acetylsalicylic acid (LDASA) has shown to improve maternal and perinatal outcomes in women at high-risk of endothelial and placental complications. However, there are no data on the effect of LDASA in preventing complications in SARS-CoV-2- infected pregnant women. To reduce SARS-CoV-2- related complications in a highly vulnerable group to the infection, we will carry out this randomized, double-blind, placebo-controlled multicentre trial in 400 SARS-CoV-2-infected pregnant women. The study main objective is to evaluate the efficacy and safety of LDASA administered up to 36 weeks of gestation in SARS-CoV-2-infected pregnant women in reducing the incidence of adverse maternal and perinatal outcomes. Pregnant women tested positive up to 32 weeks of gestation with a SARS-CoV-2 rapid antigen or PCR test and agreeing to participate, will be randomised 1:1 to receive daily LDASA (125 mg) or placebo up to 36 weeks of gestation and be followed-up until delivery.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19; SARS-CoV2 Infection
• Intervention / Treatment: Drug: Placebo; Drug: Low-dose acetylsalicylic acid

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Candelaria Serrano, Dr.; Phone Number: +34 691642368; Email: candelaria.serrano@isglobal.org
• Study Contact Backup: Name: Linda Stoeger, MSc; Email: linda.stoeger@isglobal.org

Study Locations

• Mozambique
  • Maputo, Mozambique, 257
    • Universidade Eduardo Mondlane
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08003
      • Hospital Del Mar
    • Barcelona, Catalunya, Spain, 08950
      • Hospital Sant Joan de Deu
  • Madrid
    • Torrejón de Ardoz, Madrid, Spain, 28850
      • Hospital Universitario de Torrejon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant women up to 32 weeks of gestational age
• Aged 18 years or older*

• Willing to deliver at the recruitment health facilities

  • In Mozambique, in case of age below 18 years, the participant will be asked for the assent and the informed consent will be given by the legal tutor in accordance with the national regulations.

Exclusion Criteria:

• On regular ASA treatment for pre-eclampsia prevention
• On long-term non-steroidal anti-inflammatory medication
• Bleeding disorders, mainly haemophilia, hypoprothrombinaemia orVon Willebrand's disease
• History of hypersensitivity to ASA or to any of the excipients of the investigational product.
• History of peptic ulceration, including active, chronic or recurrent gastroduodenal ulcer; recurrent gastric discomfort History of gastric bleeding or perforation after treatment with aspirin or other non-steroidal anti-inflammatory drugs
• Inability to cooperate with the requirements of the study
• Severe COVID-19 disease (with any of the following: respiratory rate > 30 breaths/min; severe respiratory distress; SpO2 ≤ 93% on room air; acute respiratory distress syndrome; sepsis with acute organ dysfunction).
• Treatment resistant hyperemesis gravidarum
• Hypersensitivity to nonsteroidal anti-inflammatory drugs or to tartrazine (cross-reaction) or to any of the excipients used in its composition.
• Asthma.
• Severe renal or hepatic insufficiency.
• Nasal polyps associated with asthma that are induced or exacerbated by aspirin.
• Severe COVID-19 disease (with any of the following: respiratory rate > 30 breaths/min; severe respiratory distress; SpO2 ≤ 93% on room air; acute respiratory distress syndrome; sepsis with acute organ dysfunction).
• Treatment resistant hyperemesis gravidarum

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDASA (n=200)	Drug: Low-dose acetylsalicylic acid; In case of being positive for SARS-CoV-2 PCR or antigen test, she will be randomised 1:1 to receive daily LDASA (125 mg) or placebo, up to 36 weeks of pregnancy.; Other Names: 125mg acetylsalicylic acid
Placebo Comparator: Placebo (n=200)	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of composite adverse maternal and perinatal adverse outcomes including miscarriage, foetal death, preeclampsia, maternal thromboembolic complications, placental abruption, preterm birth and small for gestational age.	up to 37 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of SARS-CoV-2 infection and COVID-19 disease during pregnancy	maternal	up to 37 weeks
Incidence of COVID-19-related admissions	maternal	up to 37 weeks
Incidence of all-cause admissions	maternal	up to 37 weeks
Incidence of all-cause outpatient attendances	maternal	up to 37 weeks
Mean duration of symptoms-signs of COVID-19	maternal	up to 37 weeks
Frequency and severity of adverse events	maternal	up to 37 weeks
Incidence of preeclampsia	maternal	up to 37 weeks
Incidence of maternal thromboembolic complications and placental abruption	maternal	up to 37 weeks
Maternal mortality rate	maternal	up to 37 weeks
Incidence of histological placental abnormalities in SARS-CoV-2 infected pregnant women.	maternal	up to 37 weeks
Prevalence of preterm birth (<37 weeks of gestational age)	embryo-foetal/infant	up to 37 weeks
Prevalence of small for gestational age	embryo-foetal/infant	up to 37 weeks
Prevalence of embryo and foetal losses (miscarriages and stillbirths)	embryo-foetal/infant	up to 37 weeks
Frequency of congenital malformations	embryo-foetal/infant	up to 37 weeks
Proportion of adverse perinatal outcome	embryo-foetal/infant	up to 37 weeks
Neonatal morbidity	embryo-foetal/infant	up to 37 weeks
Neonatal mortality rate	embryo-foetal/infant	up to 37 weeks

Collaborators and Investigators

• Sponsor: Barcelona Institute for Global Health
• Collaborators: Hospital del Mar; Hospital Universitario Infanta Leonor; Eduardo Mondlane University; Hospital Sant Joan de Deu; Hospital Universitario de Torrejón; Hospital Central de Maputo; Hospital Geral de Mavalane; Hospital Geral José Macamo
• Investigators: Principal Investigator: Clara Menéndez, Dr., Barcelona Institute for Global Health

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Estimated): June 9, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; COVID-19; SARS-COV2; Perinatal; Acetylsalicylic acid; ASA; Asprin
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; 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: 2022-000535-23

Drug and device information, study documents

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