Hydroxychloroquine Azithromycin COVID-19 Pregnancy Trial

Study Overview
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Brief Summary
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Up to date, and since December 31st 2019, 2 520 522 cases of COVID-19 including 176 786 deaths, have been reported worldwide. Global efforts are made to save lives and decrease morbidity by evaluating therapeutic strategies. Pregnant women with COVID-19 are at high-risk of severe complications and mortality from COVID-19 infection, due to physiologic and immune changes occurring during pregnancy. These risks include development of maternal hypoxemic respiratory failure due to severe pneumonia, hospitalization in intensive care, death; but also, fetal morbidity-mortality with chronic and/or acute fetal distress, intrauterine growth retardation, intrauterine death and neonatal morbidity, mainly due to induced preterm birth and maternal-fetal transmission. Knowledge of these epidemiologic facts on SARS-Cov-2 infection in pregnant women is currently limited to small case-series. No drug has demonstrated solid evidence in treating SARS-Cov-2 virus. Nevertheless, in vitro studies and tests in COVID-19 positive patients treated with hydroxychloroquine and azithromycin merit further evaluation. Pregnant women are systematically excluded from drug trials, and treatment options for this high-risk population remain untested. The aim of this study is to screen pregnant women presenting minor symptoms, for COVID-19 and to evaluate efficacy of hydroxychloroquine-azithromycin treatment in preventing aggravation of symptoms with development of hypoxemic respiratory failure and complications of pregnancy.

Official Title
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Efficacy Evaluation of Hydroxychloroquine Azithromycin in the Treatment of COVID-19 in Pregnant Women: an Open-label Randomized Clinical Trial

Conditions
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COVID19

Intervention / Treatment
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* Drug: Hydroxychloroquine and azithromycin treatment
* Other: conventional management of patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pregnant 18 and over monofetal pregnancy between 22+0 and 41+0 weeks of gestation presenting a positive COVID-19 RT-PCR test result after nasopharyngeal swab for one or more minor symptoms: cough, body temperature >37,3 °C, shortness of breath, diarrhea, asthenia, anosmia, taste loss, myalgia presenting no contraindication to hydroxychloroquine and azithromycin informed consent signature affiliated to social security scheme Exclusion Criteria: allergic to hydroxychloroquine or chloroquine, or azithromycin contraindication to hydroxychloroquine: retinopathy, G6PD deficiency, long QT syndrome, any other heart rhythm abnormality on pre-recruitment electrocardiogram, hypokalemia, porphyria, psoriasis. contraindication to azithromycin: long QT syndrome, liver failure, myasthenia receiving simultaneous treatments contraindicated in case of hydroxychloroquine uptake: Citalopram (Seropram), escitalopram (Seroplex), hydroxyzin (Atarax), domperidone (Motilium), piperaquine (Eurartesim), disopyramide (Isorythm, Rythmodan), hydroquinidine chlorydrate (Serecor), amiodarone (Cordarone), dronedaron (Multaq), tricyclic antidepressant, anti-infectious drugs (macrolids, fluoroquinolones, trimethoprime-sulfamethoxazole (Bactrim). receiving simultaneous treatments contraindicated in case of azithromycin uptake: Cisapride, Colchicine, Dihydroergotamine, bromocriptine, cabergoline, lisurid, pergolide, atorvastatin, ciclosporin, digoxin, simvastatin, anti-vitamine K, macrolids, ketolide hypoxemic respiratory failure due to severe pneumonia (needing supplemental oxygen) maternal disorders: Type I or II diabetes, congenital cardiopathy, liver or kidney disease, liver failure, renal failure obstetrical disorders: insulin-dependent gestational diabetes, preterm delivery threat, preterm rupture of membranes, bleeding, pre-eclampsia, gestational hypertension, gestational cholestasis

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine and azithromycin treatment<br>hydroxychloroquine 10-day course of hydroxychloroquine 200 mg tablet three times a day. To be taken orally. - azithromycin 5-day course of azithromycin 250 mg tablet twice a day on the first day of treatment, then once a day the 4 following days. | Drug: Hydroxychloroquine and azithromycin treatment<br>* hydroxychloroquine 10-day course of hydroxychloroquine 200 mg tablet three times a day. To be taken orally. - azithromycin 5-day course of azithromycin 250 mg tablet twice a day on the first day of treatment, then once a day the 4 following days.<br>Other: conventional management of patients<br>* conventional management of patients<br>|
| Active Comparator: conventional management of patients<br>Regular management of patients | Other: conventional management of patients<br>* conventional management of patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a negative RT-PCR test result to COVID-19 | Percentage of patients with a negative RT-PCR test result to COVID-19 nasopharyngeal swab at the 7th day of treatment by hydroxychloroquine and azithromycin. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal outcomes: Percentage of severe forms of the disease | percentage of severe forms of the disease | 25 weeks | 
| Newborn outcomes: Rate of newborns hospitalized in intensive care or transferred to resuscitation unit | rate of newborns hospitalized in intensive care or transferred to resuscitation unit | 25 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-Cov-2 virus, coronavirus disease, COVID-19, epidemic, pregnancy, RT-PCR, hydroxychloroquine, azithromycin, respiratory distress