Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum

Covid-19 Clinical Trial

— COVID-Preg  

Official title:

Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04410562
• Other study ID #: 2020-001587-29
• Status: Completed
• Phase: Phase 3
• Start date: May 13, 2020
• Est. completion date: October 31, 2021

Study information

• Verified date: April 2021
• Source: Barcelona Institute for Global Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes, including the timing of maternal viral exposure by gestational age, the effects of parity, age, host immune responses, coexisting medical and obstetrical conditions and the effects of treatment regimens. While further information is gathered, based on the existing evidence from other infections causing pneumonia, pregnant women should be considered to be at high risk for developing severe infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in nonpregnant adults may not be directly extrapolated to pregnant women given the special features of the pregnancy status. Thus, clinical research is urgently needed to improve the care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.

Description:

This is a randomized, double blinded, placebo-controlled multicenter clinical trial including 714 pregnant women (200 SARS-CoV-2 infected -100 symptomatic with mild disease and 100 asymptomatic- pregnant women and 514 SARS-CoV-2 uninfected pregnant women who are contacts with a SARS-CoV-2 case) with the main objectives of assessing the safety and efficacy of oral hydroxychloroquine (HCQ) in reducing maternal viral shedding by PCR, and preventing incident SARS-CoV-2 infection and disease severity. Pregnant women undergoing antenatal follow up at five maternity hospitals, presenting at least one sign and/or one mild suggestive symptoms and a positive SARS-CoV-2 PCR test, or who are contacts of a suspected or confirmed case, will be recruited and randomized 1:1 to receive HCQ orally (400 mg/day for 3 days, followed by 200 mg/day for 11 days) or placebo. Women will be followed up for the duration of the intervention. One week after intervention completion, a SARS-CoV-2 PCR test will be repeated. At delivery, the pregnancy outcome will be registered, and a cord blood sample will be collected to measure for IgG and IgM of SARS-CoV-2. A neonatal nasopharyngeal aspirate will be collected to perform PCR SARS-CoV-2 testing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: October 31, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Presenting with fever (=37.5ºC) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, taste disorder, headache) OR contact of a SARS-CoV-2 confirmed or suspected case in the past 14 days

• More than 12 weeks of gestation (dated by ultrasonography)

• Agreement to deliver in the study hospitals

Exclusion Criteria:

• Known hypersensitivity to HCQ or other 4-aminoquinoline compounds

• History of retinopathy of any aetiology

• Concomitant use of digoxin, cyclosporine, cimetidine

• Known liver disease

• Clinical history of cardiac pathology including known long QT syndrome

• Unable to cooperate with the requirements of the study

• Participating in other intervention studies

• Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours)

Related Conditions & MeSH terms

• COVID
• Covid-19
• Pregnancy Related

Intervention

Drug:
• Hydroxychloroquine
Participants will receive a bottle containing 19 tablets of study medication. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days. (400 mg/day for three days, followed by 200 mg/day for 11 days).
• Placebo
Participants will receive a bottle containing 19 tablets of placebo. They will be instructed to take two tablets for the first three days and one tablet for the following 11 days.

Locations

Country	Name	City	State
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya
Spain	Hospital de la Sant Creu i Sant Pau	Barcelona	Catalunya
Spain	Hospital del Mar	Barcelona	Catalunya
Spain	Hospital Sant Joan de Déu	Esplugues De Llobregat	Catalunya
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	HM Puerta del Sur	Móstoles	Madrid
Spain	Hospital General de Segovia	Segovia	Cartilla Y León
Spain	Hospital Universitario de Torrejón	Torrejón De Ardoz	Madrid

Sponsors (11)

Lead Sponsor	Collaborator
Barcelona Institute for Global Health	Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Fundación de investigación HM, Hospital Clinic of Barcelona, Hospital del Mar, Hospital General de Segovia, Hospital Sant Joan de Deu, Hospital Universitario Fundación Alcorcón, Hospital Universitario Infanta Leonor, Institut Català de la Salut, University Hospital of Torrejon

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of PCR confirmed cases among pregnant women	Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start	21 days after intervention
Secondary	Incidence of COVID-19 disease during pregnancy		through study completion, an average of 1 year
Secondary	Incidence of COVID-19-related admissions		through study completion, an average of 1 year
Secondary	Incidence of all-cause admissions		through study completion, an average of 1 year
Secondary	Incidence of all-cause outpatient attendances		through study completion, an average of 1 year
Secondary	Mean duration of symptoms-signs of COVID-19		through study completion, an average of 1 year
Secondary	Frequency and severity of adverse events		through study completion, an average of 1 year
Secondary	Incidence of preeclampsia		through study completion, an average of 1 year
Secondary	Incidence of gestational diabetes		through study completion, an average of 1 year
Secondary	Incidence of SARS-CoV-2 infections during pregnancy		through study completion, an average of 1 year
Secondary	Prevalence of intrauterine growth restriction		through study completion, an average of 1 year
Secondary	Maternal mortality rate		through study completion, an average of 1 year
Secondary	Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.		through study completion, an average of 1 year
Secondary	Proportion of neonates with clinical signs/symptoms of COVID-19		through study completion, an average of 1 year
Secondary	Prevalence of low birth weight (<10th centile according to local standards)		through study completion, an average of 1 year
Secondary	Prevalence of preterm birth (<37 weeks of gestational age)		through study completion, an average of 1 year
Secondary	Prevalence of embryo and foetal losses (miscarriages and stillbirths)		through study completion, an average of 1 year
Secondary	Frequency of congenital malformations		through study completion, an average of 1 year
Secondary	Proportion of adverse perinatal outcome		through study completion, an average of 1 year
Secondary	Neonatal morbidity		through study completion, an average of 1 year
Secondary	Neonatal mortality rate		through study completion, an average of 1 year