Evidence map›Paper›PMID 32150618›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020

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).

Xueting Yao, Fei Ye, Miao Zhang, Cheng Cui, Baoying Huang, Peihua Niu, Xu Liu, Li Zhao, Erdan Dong, Chunli Song and 5 more

17 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 17 registered trials, which are not on this map. Cited by 1,400 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,400citing papers in PubMed, 7 pooled it
67.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04334967 phase4suspendednot on this map

Randomized Study to Evaluate the Safety and Antiviral Efficacy of Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care Treatment

TypeinterventionalSponsorProvidence Health & ServicesRan2020 to 2022Enrolled13ConditionsCOVID-19, Corona Virus Infection, SARS-CoV-2, 2019-nCoVArmsHydroxychloroquine, Vitamin C
NCT04339816 phase3terminatednot on this map

Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care Due to Coronavirus Disease 2019 (COVID-19)- Randomised Controlled Trial

TypeinterventionalSponsorFrantisek Duska, MD, PhDRan2020 to 2020Enrolled3ConditionsCOVID-19, Respiratory FailureArmsAzithromycin, Hydroxychloroquine, Placebo
NCT04340349 early_phase1unknown statusnot on this mapstarted 2021, after this paper: background citation

Low-dose Hydroxychloroquine and Bromhexine: a Novel Regimen for COVID-19 Prophylaxis in Healthcare Professionals (ELEVATE Trial)

TypeinterventionalSponsorInstituto Nacional de RehabilitacionRan2021 to 2021Enrolled214ConditionsHydroxychloroquine, Antimalarials, Enzyme Inhibitors, Antirheumatic AgentsArmsHydroxychloroquine Sulfate, Bromhexine 8 MG
NCT04341441 phase3terminatednot on this map

Will Hydroxychloroquine Impede or Prevent COVID-19: WHIP COVID-19 Study

TypeinterventionalSponsorHenry Ford Health SystemRan2020 to 2020Enrolled624ConditionsCOVID-19, Coronavirus, Coronavirus Infections, SARS-CoV 2ArmsHydroxychloroquine - Daily Dosing, Hydroxychloroquine - Weekly Dosing, Placebo oral tablet, Monitoring Visit - Baseline, Monitoring Visit - Week 4
NCT04345289 phase3terminatednot on this map

Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial

TypeinterventionalSponsorThomas BenfieldRan2020 to 2021Enrolled147ConditionsCOVID, Corona Virus Infection, Viral PneumoniaArmsConvalescent anti-SARS-CoV-2 plasma, Infusion placebo
NCT04353271 phase2 / phase3terminatednot on this map

A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics

TypeinterventionalSponsorUniversity of South AlabamaRan2020 to 2020Enrolled3ConditionsCovid 19, Corona Virus InfectionArmsHydroxychloroquine, Placebo
NCT04354441 phase2withdrawnnot on this map

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

TypeinterventionalSponsorSir Mortimer B. Davis - Jewish General HospitalRan2020 to 2020Enrolled0ConditionsCOVID-19, SARS-CoV-2, Pregnant Women, HydroxychloroquineArmshydroxychloroquine sulfate 200 MG, Placebo oral tablet
NCT04359095 phase2 / phase3completednot on this map

Effectiveness and Safety of Medical Treatment for SARS-CoV-2 (COVID-19) in Colombia: A Pragmatic Randomized Controlled Trial

TypeinterventionalSponsorUniversidad Nacional de ColombiaRan2020 to 2021Enrolled650ConditionsCOVID-19ArmsEmtricitabine/tenofovir, Colchicine Pill, Rosuvastatin, Standard treatment
NCT04361318 phase2 / phase3unknown statusnot on this map

Clinical Trial Evaluating Safety and Efficacy of Hydroxychloroquine and Nitazoxanide Combination as Adjuvant Therapy in Covid-19 Newly Diagnosed Egyptian Patients: A Tanta University Hope

TypeinterventionalSponsorTanta UniversityRan2020 to 2020Enrolled100ConditionsCOVID-19ArmsHydroxychloroquine plus Nitazoxanide, Standard care
NCT04369989 terminatednot on this map

Observational Study of COVID-19 Treatment Efficacy

TypeobservationalSponsorOSF Healthcare SystemRan2020 to 2021Enrolled250ConditionsCoronavirus, Coronavirus Infection, Corona Virus Infection, COVIDArmsNo intervention
NCT04370782 phase4completednot on this map

A Randomized Study Evaluating the Safety and Efficacy of Hydroxychloroquine and Zinc in Combination With Either Azithromycin or Doxycycline for the Treatment of COVID-19 in the Outpatient Setting

TypeinterventionalSponsorSt. Francis Hospital, New YorkRan2020 to 2020Enrolled18ConditionsCOVID-19ArmsHydroxychloroquine, Azithromycin, Zinc Sulfate, Doxycycline
NCT04380870 unknown statusnot on this map

Describing Chinese Herbal Medicine Telehealth Care for Symptoms Related to Infectious Diseases Such as COVID-19: A Descriptive, Longitudinal, Pragmatic Cohort Study

TypeobservationalSponsorCenter for Integrated CareRan2020 to 2025Enrolled500ConditionsCoronavirus InfectionArmsChinese Herbal Medicine
NCT04394416 phase3terminatednot on this map

Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19

TypeinterventionalSponsorUniversity of Maryland, BaltimoreRan2020 to 2025Enrolled21ConditionsCOVID-19ArmsImatinib, Placebo oral tablet
NCT04434144 completednot on this map

A Comparative Observational Study on Ivermectin and Hydroxychloroquine on the COVID19 Patients in Bangladesh

Typeobservational_patient_registrySponsorUpazila Health & Family Planning Officer's (UHFPO) Office, Chakoria, Cox's BazarRan2020 to 2020Enrolled116ConditionsIvermectin, Hydroxychloroquine, COVID19ArmsIvermectin + Doxycycline, Hydroxychloroquine + Azithromycin
NCT04491994 phase3completednot on this map

Clearing the Fog: Is HCQ Effective in Reducing COVID-19 progression-a Randomized Controlled Trial

TypeinterventionalSponsorUNICEFRan2020 to 2020Enrolled540ConditionsCovid19, ProgressionArmsHCQ
NCT04627467 phase2completednot on this map

Prophylaxis With Chloroquine in Health Personnel Exposed to Infection With Coronavirus Disease 2019 (COVID-19)

TypeinterventionalSponsorFundacion Clinica Valle del LiliRan2020 to 2021Enrolled3,217ConditionsCovid19ArmsChloroquine
NCT04654416 completednot on this map

Clinical Outcome of Patients With COVID-19 Pneumonia Treated With Corticosteroids and Colchicine in Colombia

TypeobservationalSponsorClínica Medellín - Grupo QuirónsaludRan2020 to 2020Enrolled301ConditionsCovid-19ArmsCorticosteroid with or without colchicine
3 · Its place in the literature

Who cites it

1,400 citing papers in PubMed, 7 syntheses or guidelines pooled it, 2,765 citations in OpenAlex.

  1. Pooled it
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  11. One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
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  12. Trial
  13. Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023
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  15. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2022
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1,340 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Xueting YaoDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Fei YeNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Miao ZhangDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Cheng CuiDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Baoying HuangNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Peihua NiuNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Xu LiuDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Li ZhaoNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Erdan DongDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
Chunli SongDepartment of Orthopedics, Peking University Third Hospital, Beijing, China.
Siyan ZhanResearch Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
Roujian LuNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Haiyan LiDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Wenjie TanNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Dongyang LiuDrug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
National Institute for Viral Disease Control and Prevention · CNPeking University · CNPeking University Third Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

methodsThe pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2-infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug's safety profile.

resultsHydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

conclusionsHydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

Indexed as

AnimalsAntiviral AgentsBetacoronavirusCell LineChlorocebus aethiopsChloroquineCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentHydroxychloroquineLungPandemicsPneumonia, ViralSARS-CoV-2Severe Acute Respiratory SyndromeVero CellsAntiviral AgentsChloroquineHydroxychloroquinechloroquinehydroxychloroquineSARS-CoV-2

Identifiers

PMID32150618
PMCPMC7108130
OpenAlexW3009577418

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

and 11 more above

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.