Clinical trial NCT04365231: Hydroxychloroquine Azithromycin COVID-19 Pregnancy Trial
Official title: Efficacy Evaluation of Hydroxychloroquine Azithromycin in the Treatment of COVID-19 in Pregnant Women: an Open-label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: COVID19
Keywords: SARS-Cov-2 virus
coronavirus disease
COVID-19
epidemic
pregnancy
RT-PCR
hydroxychloroquine
azithromycin
respiratory distress
Lead sponsor: Hospital St. Joseph, Marseille, France
Sponsor class: OTHER
First posted: 2020-04-28
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients with a negative RT-PCR test result to COVID-19
timeFrame: 7 days
Secondary outcomes:
measure: Maternal outcomes: Percentage of severe forms of the disease
timeFrame: 25 weeks
measure: Newborn outcomes: Rate of newborns hospitalized in intensive care or transferred to resuscitation unit
timeFrame: 25 weeks
Other outcomes:
Locations:
Study officials:
References: