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

Sponsor

Barcelona Institute for Global Health (Other)

Overall Status

Completed

CT.gov ID

NCT04410562

Collaborator

Hospital Clinic of Barcelona (Other), Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (Other), University Hospital of Torrejon (Other), Fundación de investigación HM (Other), Hospital Sant Joan de Deu (Other), Hospital del Mar (Other), Hospital Universitario Infanta Leonor (Other), Hospital Universitario Fundación Alcorcón (Other), Hospital General de Segovia (Other), Institut Català de la Salut (Other)

129

Enrollment

Locations

Arms

17.6

Actual Duration (Months)

14.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Related COVID Covid-19	Drug: Hydroxychloroquine Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

129 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blinded, placebo-controlled multicentre clinical trial.Randomized, double-blinded, placebo-controlled multicentre clinical trial.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 13, 2020

Actual Primary Completion Date :

Jun 30, 2021

Actual Study Completion Date :

Oct 31, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Number of PCR confirmed cases among pregnant women [21 days after intervention]
Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital General de Segovia	Segovia	Cartilla Y León	Spain	40002
2	Hospital del Mar	Barcelona	Catalunya	Spain	08003
3	Hospital Clínic de Barcelona	Barcelona	Catalunya	Spain	08036
4	Hospital de la Sant Creu i Sant Pau	Barcelona	Catalunya	Spain	08041
5	Hospital Sant Joan de Déu	Esplugues De Llobregat	Catalunya	Spain	08950
6	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid	Spain	28922
7	HM Puerta del Sur	Móstoles	Madrid	Spain	28938
8	Hospital Universitario de Torrejón	Torrejón De Ardoz	Madrid	Spain	28850
9	Hospital Universitario Infanta Leonor	Madrid		Spain	28031