Effect of Hydroxychloroquine in COVID-19 Positive Pregnant Women

Study Overview
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Brief Summary
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COVID-19 was declared a pandemic on March 11th. Efforts to save lives are essential as we will face increasing morbidity with rising demands on health care resources. Since pregnant women with COVID-19 have systematically been excluded from drug trials, potential treatment options for these high-risk individuals remain untested. The aim of our trial is to determine whether hydroxychloroquine given to COVID-19 positive pregnant women can reduce COVID-19-related hospital admissions, thereby allowing women to stay at home while limiting utilization of hospital resources and resulting exposure of health care providers.

Detailed Description
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Due to physiologic and immune changes, pregnant women are at high risk of severe complications and mortality from COVID-19 infections. Despite this, epidemiologic data on SARS-CoV-2 infection in pregnancy is currently limited to small case-series describing a clinical course ranging from mild to critical illness requiring extracorporeal membrane oxygenation. Chloroquine and hydroxychloroquine (HCQ) have demonstrated activity against SARS-coronaviruses in laboratory studies and are being tested in COVID-19 positive patients. HCQ appears more promising than chloroquine due to its greater effectiveness against SARS-CoV-2 in vitro and better safety profile. To date, pregnant women have been systematically excluded from trials conducted in the general outpatient population. Thus, we will carry out a randomized, placebo-controlled, double blinded trial of HCQ (considered safe in pregnancy in pregnant women with early COVID-19 infection across Canada to evaluate its effect in reducing COVID-19-related hospitalizations. This outpatient intervention is of paramount importance as its goal is to avoid overloading emergency rooms, obstetric triage, inpatient wards and critical care units. Upon completion of 6-month, our results can be directly applied to clinical care.

Official Title
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Randomized Trial Evaluating Effect of Outpatient Hydroxychloroquine on Reducing Hospital Admissions in Pregnant Women With SARS-CoV-2 Infection: HyPreC Trial

Conditions
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COVID-19, SARS-CoV-2, Pregnant Women, Hydroxychloroquine

Intervention / Treatment
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* Drug: hydroxychloroquine sulfate 200 MG
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with a self-reported live pregnancy >14 weeks Presently in the outpatient setting (i.e. not admitted to the hospital) Tested positive for COVID-19 within last 7 days Must be living in Canada Exclusion Criteria: Known glucose-6-phosphate dehydrogenase (G6PD) deficiency Known cardiac disease (or under investigation) Currently taking medication contraindicated as per Health Canada list for hydroxychloroquine Known retinopathy Known hypersensitivity to 4-aminoquinoline compounds Already taking hydroxychloroquine Unwilling to answer follow-up questionnaires Currently in labor Inpatient women at time of COVID-19 diagnosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 to receive either the study medication (hydroxychloroquine) or an identical-looking placebo. Randomization will be in blocks of 4-6, stratified by province.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hydroxychloroquine<br>10-day course of hydroxychloroquine 200 mg tablet twice a day. To be taken orally. | Drug: hydroxychloroquine sulfate 200 MG<br>* Hydroxychloroquine sulfate (Plaquenil) 2MG will be taken twice a day for 10 days. Participants will be couriered the medication upon giving consent and will start taking the medication immediately.<br>|
| Placebo Comparator: Placebo<br>An identical appearing placebo. To be taken orally twice a day for 10-days. | Drug: Placebo oral tablet<br>* Placebo that is identical in appearance to the study medication will be taken twice a day for 10 days. It will be couriered to participants upon giving consent. They will start taking the medication immediately.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19-related hospital admissions | COVID-19-related hospital admissions will be reported by the participants throughout pregnancy until delivery. | Hospital Admission at any point from study enrollment to delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms related to COVID-19 infection | Measurement of reported symptoms using a validated questionnaire on Day 3, 7, 10, and every 2 weeks. The FLU-PRO Questionnaire instructs respondents to rate the severity of 37 influenza symptoms over the past 24 hours, including those related to the nose, throat, eye, chest, head, stomach, fatigue, and body aches/pains. For 32 of 37 items, respondents rated the severity of each symptom on 5-point Likert-type scales from 0 (Not at all), 1 (A little bit), 2 (Somewhat), 3 (Quite a bit), to 4 (Very much). For the five remaining items, severity is expressed as frequency of occurrence: vomiting or diarrhea (0 times, 1 time, 2 times, 3 times, or 4 or more times), and sneezing, coughing, and coughed up mucus or phlegm on a scale from 0 (Never) to 4 (Always), with higher scores indicating more severe symptoms. | Participants will be contacted at day 3, 7, and 10 post-randomization, and every 2 weeks up to to delivery | 
| Adverse Events | Side effects related to hydroxychloqoruine | Participants will be contacted at day 3, 7, and 10 post-randomization, and every 2 weeks up to to delivery | 
| Maternal outcomes | Type of delivery (elective non-urgent cesarean, elective urgent cesarean section, non-elective cesarean within labor, instrumental vaginal, spontaneous vaginal) | Participants will be contacted within 2 weeks after delivery to obtain information about their labor and delivery. | 
| Maternal outcomes | If had cesarean delivery, indication for cesarean section | Participants will be contacted within 2 weeks after delivery to obtain information about their labor and delivery. | 
| Maternal outcomes | Miscarriage or stillbirth (Yes/No) | Participants will be contacted within 2 weeks after delivery to obtain information about their labor and delivery. | 
| Maternal outcomes | Labor induction or augmentation (Yes/No) and indication | Participants will be contacted within 2 weeks after delivery to obtain information about their labor and delivery. | 
| Maternal outcomes | Epidural use (Yes/No) | Participants will be contacted within 2 weeks after delivery to obtain information about their labor and delivery. | 
| Newborn outcomes | Gestational age at delivery (weeks) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | Sex (female/male) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | Birth weight (kg) Birth weight (kg) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | Need for resuscitation (Yes/No) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | NICU admission (Yes/No) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | Medical conditions (jaundice, IVH, RDS, pneumothorax, PDA, NEC) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 
| Newborn outcomes | Current disposition of baby (home or hospital) | Participants will be contacted within 2 weeks after delivery to obtain information about their baby. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, Pregnancy, hydroxychloroquine