SARS-CoV-2 and Acetylsalicylic Acid (SARA)

Study Overview
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Brief Summary
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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.

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

Conditions
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SARS-CoV2 Infection, Covid19

Intervention / Treatment
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* Drug: Low-dose acetylsalicylic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blind placebo-controlled multicentre clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDASA (n=200)<br> | Drug: Low-dose acetylsalicylic acid<br>* 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.<br>* Other names: 125mg acetylsalicylic acid;|
| Placebo Comparator: Placebo (n=200)<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-COV2, Acetylsalicylic acid, Asprin, ASA, COVID-19, Perinatal, Pregnancy