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

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.

Study Overview

• Status: Completed
• Conditions: Covid-19; Pregnancy Related; COVID
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Cartilla Y León
    • Segovia, Cartilla Y León, Spain, 40002
      • Hospital General de Segovia
  • Catalunya
    • Barcelona, Catalunya, Spain, 08003
      • Hospital Del Mar
    • Barcelona, Catalunya, Spain, 08036
      • Hospital Clínic de Barcelona
    • Barcelona, Catalunya, Spain, 08041
      • Hospital de la Sant Creu i Sant Pau
    • Esplugues De Llobregat, Catalunya, Spain, 08950
      • Hospital Sant Joan de Déu
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Hospital Universitario Fundacion Alcorcon
    • Móstoles, Madrid, Spain, 28938
      • Hm Puerta Del Sur
    • Torrejón De Ardoz, Madrid, Spain, 28850
      • Hospital Universitario de Torrejon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hydroxychloroquine; Participants will be then randomized in a 1:1 ratio to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days)	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).; Other Names: Dolquine
PLACEBO_COMPARATOR: Placebo; Participants will be then randomized in a 1:1 ratio to placebo (2 tablets for three days, followed by one tablet for 11 days).	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Incidence of COVID-19 disease during pregnancy	through study completion, an average of 1 year
Incidence of COVID-19-related admissions	through study completion, an average of 1 year
Incidence of all-cause admissions	through study completion, an average of 1 year
Incidence of all-cause outpatient attendances	through study completion, an average of 1 year
Mean duration of symptoms-signs of COVID-19	through study completion, an average of 1 year
Frequency and severity of adverse events	through study completion, an average of 1 year
Incidence of preeclampsia	through study completion, an average of 1 year
Incidence of gestational diabetes	through study completion, an average of 1 year
Incidence of SARS-CoV-2 infections during pregnancy	through study completion, an average of 1 year
Prevalence of intrauterine growth restriction	through study completion, an average of 1 year
Maternal mortality rate	through study completion, an average of 1 year
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
Proportion of neonates with clinical signs/symptoms of COVID-19	through study completion, an average of 1 year
Prevalence of low birth weight (<10th centile according to local standards)	through study completion, an average of 1 year
Prevalence of preterm birth (<37 weeks of gestational age)	through study completion, an average of 1 year
Prevalence of embryo and foetal losses (miscarriages and stillbirths)	through study completion, an average of 1 year
Frequency of congenital malformations	through study completion, an average of 1 year
Proportion of adverse perinatal outcome	through study completion, an average of 1 year
Neonatal morbidity	through study completion, an average of 1 year
Neonatal mortality rate	through study completion, an average of 1 year

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 13, 2020
• Primary Completion (ACTUAL): June 30, 2021
• Study Completion (ACTUAL): October 31, 2021

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (ACTUAL): June 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: pregnancy; coronavirus; hydroxychloroquine; covid-19
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 2020-001587-29

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: It would be shared at time of publication.
• IPD Sharing Time Frame: By the end of study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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