Clinical trial NCT04410562: Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum
Official title: Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy and Postpartum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy Related
COVID
Covid-19
Keywords: pregnancy
covid-19
coronavirus
hydroxychloroquine
Lead sponsor: Barcelona Institute for Global Health
Sponsor class: OTHER
Collaborators: name: Hospital Clinic of Barcelona
name: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: University Hospital of Torrejon
name: Fundación de investigación HM
name: Hospital Sant Joan de Deu
name: Hospital del Mar
name: Hospital Universitario Infanta Leonor
name: Hospital Universitario Fundación Alcorcón
name: Hospital General de Segovia
name: Institut Català de la Salut
First posted: 2020-06-01
Enrollment: 129
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, placebo-controlled multicentre clinical trial.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of PCR confirmed cases among pregnant women
timeFrame: 21 days after intervention
Secondary outcomes:
measure: Incidence of COVID-19 disease during pregnancy
timeFrame: through study completion, an average of 1 year
measure: Incidence of COVID-19-related admissions
timeFrame: through study completion, an average of 1 year
measure: Incidence of all-cause admissions
timeFrame: through study completion, an average of 1 year
measure: Incidence of all-cause outpatient attendances
timeFrame: through study completion, an average of 1 year
measure: Mean duration of symptoms-signs of COVID-19
timeFrame: through study completion, an average of 1 year
measure: Frequency and severity of adverse events
timeFrame: through study completion, an average of 1 year
measure: Incidence of preeclampsia
timeFrame: through study completion, an average of 1 year
measure: Incidence of gestational diabetes
timeFrame: through study completion, an average of 1 year
measure: Incidence of SARS-CoV-2 infections during pregnancy
timeFrame: through study completion, an average of 1 year
measure: Prevalence of intrauterine growth restriction
timeFrame: through study completion, an average of 1 year
measure: Maternal mortality rate
timeFrame: through study completion, an average of 1 year
measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.
timeFrame: through study completion, an average of 1 year
measure: Proportion of neonates with clinical signs/symptoms of COVID-19
timeFrame: through study completion, an average of 1 year
measure: Prevalence of low birth weight (<10th centile according to local standards)
timeFrame: through study completion, an average of 1 year
measure: Prevalence of preterm birth (<37 weeks of gestational age)
timeFrame: through study completion, an average of 1 year
measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths)
timeFrame: through study completion, an average of 1 year
measure: Frequency of congenital malformations
timeFrame: through study completion, an average of 1 year
measure: Proportion of adverse perinatal outcome
timeFrame: through study completion, an average of 1 year
measure: Neonatal morbidity
timeFrame: through study completion, an average of 1 year
measure: Neonatal mortality rate
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Segovia
country: Spain
facility: Hospital General de Segovia
state: Cartilla Y León
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Catalunya
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya
city: Barcelona
country: Spain
facility: Hospital de la Sant Creu i Sant Pau
state: Catalunya
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
state: Catalunya
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Móstoles
country: Spain
facility: HM Puerta del Sur
state: Madrid
city: Torrejón De Ardoz
country: Spain
facility: Hospital Universitario de Torrejón
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
Study officials:
References:
citation: Gonzalez R, Garcia-Otero L, Pons-Duran C, Marban-Castro E, Gonce A, Llurba E, Gil MDM, Rodriguez-Zambrano MA, Chen H, Ramirez M, Bardaji A, Menendez C. Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg): a structured summary of a study protocol for a randomised placebo controlled trial. Trials. 2020 Jul 2;21(1):607. doi: 10.1186/s13063-020-04557-y.