Effect of Hydroxychloroquine in COVID-19 Positive Pregnant Women

NCT ID: NCT04354441

Last Updated: 2020-06-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-31

Study Completion Date

2020-05-31

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.

Conditions

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COVID-19 SARS-CoV-2 Pregnant Women Hydroxychloroquine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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hydroxychloroquine

10-day course of hydroxychloroquine 200 mg tablet twice a day. To be taken orally.

Group Type EXPERIMENTAL

hydroxychloroquine sulfate 200 MG

Intervention Type DRUG

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.

Placebo

An identical appearing placebo. To be taken orally twice a day for 10-days.

Group Type PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type DRUG

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.

Interventions

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hydroxychloroquine sulfate 200 MG

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.

Intervention Type DRUG

Placebo oral tablet

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.

Intervention Type DRUG

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sir Mortimer B. Davis - Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Haim Abenhaim

Obstetrician & gynecologist; Director of Perinatal Research

Responsibility Role PRINCIPAL_INVESTIGATOR

References

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Lapinsky SE. Management of Acute Respiratory Failure in Pregnancy. Semin Respir Crit Care Med. 2017 Apr;38(2):201-207. doi: 10.1055/s-0037-1600909. Epub 2017 May 22.

Reference Type BACKGROUND
PMID: 28561251 (View on PubMed)

Callaghan WM, Creanga AA, Jamieson DJ. Pregnancy-Related Mortality Resulting From Influenza in the United States During the 2009-2010 Pandemic. Obstet Gynecol. 2015 Sep;126(3):486-490. doi: 10.1097/AOG.0000000000000996.

Reference Type BACKGROUND
PMID: 26244541 (View on PubMed)

Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010 Jun;63(6):425-33. doi: 10.1111/j.1600-0897.2010.00836.x. Epub 2010 Mar 29.

Reference Type BACKGROUND
PMID: 20367629 (View on PubMed)

Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D, Gong Q, Liao J, Yang H, Hou W, Zhang Y. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020 Mar 7;395(10226):809-815. doi: 10.1016/S0140-6736(20)30360-3. Epub 2020 Feb 12.

Reference Type BACKGROUND
PMID: 32151335 (View on PubMed)

Liu Y, Chen H, Tang K, Guo Y. Withdrawn: Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020 Mar 5:S0163-4453(20)30109-2. doi: 10.1016/j.jinf.2020.02.028. Online ahead of print.

Reference Type BACKGROUND
PMID: 32145216 (View on PubMed)

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. No abstract available.

Reference Type BACKGROUND
PMID: 32194981 (View on PubMed)

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.

Reference Type BACKGROUND
PMID: 32150618 (View on PubMed)

Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, Doria A, Fischer-Betz R, Forger F, Moraes-Fontes MF, Khamashta M, King J, Lojacono A, Marchiori F, Meroni PL, Mosca M, Motta M, Ostensen M, Pamfil C, Raio L, Schneider M, Svenungsson E, Tektonidou M, Yavuz S, Boumpas D, Tincani A. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017 Mar;76(3):476-485. doi: 10.1136/annrheumdis-2016-209770. Epub 2016 Jul 25.

Reference Type BACKGROUND
PMID: 27457513 (View on PubMed)

Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, Khamashta MA, Kim MY, Saxena A, Friedman D, Llanos C, Piette JC, Buyon JP. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation. 2012 Jul 3;126(1):76-82. doi: 10.1161/CIRCULATIONAHA.111.089268. Epub 2012 May 24.

Reference Type BACKGROUND
PMID: 22626746 (View on PubMed)

Costedoat-Chalumeau N, Amoura Z, Duhaut P, Huong DL, Sebbough D, Wechsler B, Vauthier D, Denjoy I, Lupoglazoff JM, Piette JC. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum. 2003 Nov;48(11):3207-11. doi: 10.1002/art.11304.

Reference Type BACKGROUND
PMID: 14613284 (View on PubMed)

Costedoat-Chalumeau N, Amoura Z, Huong DL, Lechat P, Piette JC. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases. Review of the literature. Autoimmun Rev. 2005 Feb;4(2):111-5. doi: 10.1016/j.autrev.2004.11.009. Epub 2004 Dec 14.

Reference Type BACKGROUND
PMID: 15722258 (View on PubMed)

Other Identifiers

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1, March 30, 2020

Identifier Type: -

Identifier Source: org_study_id

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