Prevention of COVID19 Infection in Nursing Homes by Chemoprophylaxis With Hydroxychloroquine (PREVICHARM)

NCT ID: NCT04400019

Last Updated: 2020-09-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 1930 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2021-04-01

Brief Summary

Professionals and residents of nursing homes are one of the most vulnerable groups in this public health crisis of COVID-19, since they have the highest rate of positives for COVID-19, despite the restriction measures carried out, such as prohibition of family visits to these centers, the infection occurs by cross transmission with the care staff of the centers, or with other residents.

At the moment, there are no clinical trials to test the hypothesis that hydroxychloroquine is effective in coronavirus treatment. Although what has been observed is a better prognosis in infected patients, since this drug inhibits the replication of the virus and its expansion to other tissues.

This study is a clinical trial to test the effectiveness of hydroxychloroquine as a preventive drug for SARS-CoV-2 infection. This drug will be applied to 1050 people residing in nursing home care and 880 professionals who work in close contact with these people and who have not yet contracted the infection.

This project will be carried out in the territories of Madrid, Navarra, Aragon and Andalusia (Spain).

Hydroxychloroquine is a widely known drug that is used in two scenarios, against autoimmune diseases, such as lupus or rheumatoid arthritis, and as an antimalarial drug.

It is also intended to demonstrate that the presumed reduction in viral load that would be obtained with hydroxychloroquine prophylaxis, would have no effect in development of immunity against the virus. This fact can create a new paradigm for the de-escalation of the confinement to which the population has been subjected to stop the virus spread, allowing the development of general immunity in controlled populations until reaching total immunity.

In addition to testing the effect of this drug, a non-pharmacological intervention based on a safety record will be tested in the management of infection on nursing home, to assess its effectiveness in detecting risk areas or bad practices carried out in this vulnerable environment.

The study is led by researchers of the Institute of Biomedicine of Malaga (Spain), and has obtained a financing of 1,024,199 euros from Carlos III Health Institute (Spain).

The period of execution of the clinical trial is one year, and with this intervention, the intention is to reduce cross-infection in residents by a minimum threshold of 15%, as well as to decrease infection in the professionals.

Detailed Description

The objective of this study is to evaluate the effectiveness of hydroxychloroquine chemoprophylaxis in healthcare personnel and residents:

1. the incidence of secondary cases of SARS-CoV-2 infection in residents

2. the incidence of SARS-CoV-2 infection in the staff. To assess the effect of measures to promote infection control. Design: Controlled, randomized, triple-blind cluster multicentre trial. Subjects: Institutionalized older people and nursing homes staff in four Autonomous Communities.

Sample: 880 professionals, 1050 residents in 84 residences. They will be given 800mg of hydorxychloroquine the first day and 400mg in the subsequent four days. Nasopharyngeal exudate will be taken for baseline RT-PCR, and at six and 14 days after the adminsitration of hydroxychloroquine.

Mortality, compliance, safety, symptoms, and hospital admission will be evaluated secondarily.

The highest risk group for SARS-CoV-2 infection is that of people over 60 years of age, with cardiovascular disease, diabetes, COPD and immunosuppression, reaching up to 32% of those infected. But, in addition, the impact is especially insidious among institutionalized older people. The Spanish MInistry of Health has developed some regulations with measures to curb the impact in this context. WHO places institutionalized people as a very vulnerable group due to their permanent close contact with other people in the residence, the abundance of group activities, the presence of people with cognitive impairment and the need for help for their activities of daily living, which involves close physical contact with healthcare personnel. Even the interventions for preventing and controlling the infection could seriously affect the mental health and well-being of this vulnerable people, even if they do not contract the infection. In the province of Malaga (Spain), a checklist has been developed consisting of 13 items related to knowledge and compliance with the rules of prevention, self-protection, isolation and circuits, carried out by case management nurses. This instrument contains many of the WHO recommendations and may be an element that could make a difference in this context.

A significant proportion of those infected are known to have had close contact with probable or confirmed SARS-CoV-2 cases. In institutionalized people, the main source of contact (once family visits have been eliminated) is caused by cross-contamination with the care staff who provide direct care or other infected residents. In nursing homes, staff ratios are much more limited than in acute care hospitals (aggravated by the demand for professionals due to the epidemic). Furthermore, the possibility of isolation of infected patients is very limited: On average, residences only have 15% of their rooms prepared for isolation.

Among the various therapeutic strategies being tested, the use of hydroxychloroquine (HCQ) emerges as a viable option, albeit with limitations in the studies. This use has already been proposed for a long time due to its potential antiviral action, since it alkalinizes the cellular pH necessary for binding of the virus to the host cell and interferes with glycosylation of ECA2 receptors and blocks endosomatic transport of the virus. HCQ administered in a safe dose range is distributed throughout the body, including the lung parenchyma after oral administration, with few adverse effects. Compared to the antivirals under study for SARS-CoV-2 infection, it is much more feasible in real clinical practice conditions to access HCQ, a drug on which, in addition, there is enormous experience, its safety is well known, It is funded by the National Health System (NHS), it is cheap and accessible on the NHS. There are currently several clinical trials underway and a consensus has been developed that recommends their use in patients with SARS-CoV-2 pneumonia. Regarding the prophylactic use of HCQ, another trial in Spain has just started to use it in a "test and treat" strategy in patients among the general population, but it does not directly affect the institutionalized population. Our study aims to explore whether the administration of chemoprophylaxis in nursing homes is a protective strategy for both institutionalized people and the professionals themselves.

This is an controlled, randomized, triple-blind cluster study.The primary target population of the study consists of professionals who provide direct care in nursing homes (nursing assistants and nurses) and institutionalized older people.

The sampling frame will be integrated by the Communities of Andalusia, Madrid, Aragon and the Autonomous Community of Navarra. A conservative sample calculation has been designed, due to the current uncertainty regarding incidence. The incidence of Andalusia has been taken as the lower limit and the incidence provided in the study by Kimball et al. as an upper limit, and bearing in mind that many nursing homes are taking measures to isolate and relocate residents. To decrease the minimum infection rate in residents from 25% to 10% (delta = -0.15), with an alpha of 0.05, a power of 80%, assuming a minimum of 13 residents per cluster with a CCI of 0.1, with a replacement rate of losses of 25%, a total of 1050 residents would be necessary, with 7 clusters in each step, distributed in a total of 84 nursing homes. Regarding workers, taking the references from Andalusia and the study by McMichael et al. to decrease the minimum infection rate in professionals from 18% to 5% (delta = -0.13), with the same power parameters, assuming a minimum of 10 professionals per cluster with a CCI 0.1, and a replacement rate of 5% 880 professionals with the same number of clusters and nursing homes are required.

The PREVICHARM study was originally conceived at the end of March 2020 as a randomized clinical trial by stepped wedge clusters, since it was a methodological path that at that time allowed all participating subjects to receive the drug as chemoprophylaxis, in a staggered manner, without losing the comparison with a control group. After the evolution of the pandemic and the research around HCQ, the research team has considered the need to introduce some modifications in the design, to eliminate the staggering in the trial sequence, maintaining the design controlled and randomized by clusters, but, introducing an assignment of two parallel arms by triple blind to, on the one hand, have a totally blinded design that improves the robustness of the conclusions and, on the other, simplify the operationalization of the trial and thus further strengthen its feasibility. A criterion on the period of time necessary for inclusion has also been updated, reducing it to 8 days, in light of current knowledge on the predictive value of PCR in the course of infection in exposed patients.

The modifications do not affect the objectives, or hypotheses, or the outcomes, or the evaluation procedures thereof, or the follow-ups or the evaluation of the safety of the trial.

Variables: Sociodemographic, adjustment and control of confounders (Cluster, follow-up time, hours worked by each professional during the study, gradient of application of non-pharmacological measures); Primary endpoints: Number of secondary cases of SARS-CoV2 infection among residents, and SARS-CoV-2 infection in caregivers who provide direct care; Secondary endpoints: mortality, compliance with treatment, symptoms of SARS-CoV-2 infection, hospital admission of personnel and adverse events.

All the nursing homes in the province will be invited to participate and after randomization, the phased inclusion of residences will begin, requesting the consent of professionals to be included and proceeding to collect basal exudate and study variables. In the randomized nursing homes in each step as an intervention, the HCQ regimen will be provided and the nasopharyngeal exudate follow-up will be performed for RT-PCR at 6 and 14 days. In those in the control group step, an exudate will be collected on the same days than intervention group. Once enrolled, subjects will receive a double naso-oro-pharyngeal swab and will be provided blinded medication (HCQ or placebo, as appropriate) for the entire chemoprophylaxis cycle. Subsequently, smears will be taken again at 6 and 14 days. The sample collection procedure will be standardized through the protocol developed by the Ministry of Health and technicians will be trained in advance in its performance.

The technicians will go to each residence according to a cadence pre-established by the research team.

Adverse events will be monitored at each weekly visit using a standardized procedure (gastrointestinal disorders, appetite disturbances, hypoglycemia, weight loss, decreased visual acuity, photophobia, impaired visual accommodation with symptoms of blurred vision, deafness, tinnitus, and vertigo, muscle weakness, symptoms of liver and kidney disorders, neurological disorders). Serious and non-serious adverse events will be distinguished and will be notified by means of a standard procedure to the Research Ethics Committee, and to the Spanish Agency for Medicines and Health Products. An insurance policy has been contracted for risk coverage.

The study will comply with all the precepts of the Declaration of Helsinki and its subsequent revisions, as well as the Standards of Good Practice. Participants will be informed of the characteristics and purpose of the study and will be asked for informed consent in accordance with the regulations in force in Spain using the form and the corresponding information sheet. The study has been approved by the Malaga Provincial Research Ethics Committee and the Spanish Agency for Medicines and Health Products, as well as the participating institutions.

All the trial monitoring process and pharmacovigilance will be carried out by the Clinical Trial Units of the Spanish Clinical Research Network of the participating Centers.

Exploratory data analysis, bivariate analysis (chi square, Student t, ANOVA or their non-parametric equivalents in case of non-normality) will be performed and the main hypothesis will be tested using generalized linear binomial and Poisson models, also taking the cluster, as random effects factor, and time as a fixed factor. Intrasubject analyzes will be carried out using mixed generalized linear models. All the analyses will be performed by intention to treat, using multiple imputation models.

The total estimated duration is a maximum of 12 months.

Conditions

Sars-CoV2; Coronavirus Infection; Prevention & Control; Nursing Home; Hydroxychloroquine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Tracking control

According to the randomization process described, those nursing homes assigned to the control arm of the trial will receive the same treatment as those assigned to the intervention group, except for the medication, which will be a masked placebo.

The study is triple blind, so neither the professionals who carry out the follow-up, nor the patients, nor the person in charge of analyzing the data, know to which group each nursing home belongs.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

The dose to be used as chemoprophylaxis will be 800mg of Hydroxychloroquine (HCQ) on the first day and 400mg during the subsequent four days. Participating subjects will be followed up at 6, 14 and 28 days.

Group Type: EXPERIMENTAL

Hydroxychloroquine Only Product in Oral Dose Form

Intervention Type: DRUG

The dose to be used as chemoprophylaxis will be 800mg of HCQ on the first day and 400mg for the following four days.

Interventions

Hydroxychloroquine Only Product in Oral Dose Form

The dose to be used as chemoprophylaxis will be 800mg of HCQ on the first day and 400mg for the following four days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Institutionalized people in nurswing homes since the beginning of the COVID19 epidemic who do not have the infection present at the time of entering into the study.
• Healthcare professionals who provide direct care (nursing assistants and registered nurses) to institutionalized older people in nursing homes with confirmed cases of COVID19 during the past 8 days.
• Subjects that give their consent to participate in the study or that it be obtained from their representative / legal guardian.

Exclusion Criteria

• Staff members who do not provide direct care to residents.
• Residents with active SARS-CoV-2 infection present, or with symptoms compatible with COVID19 confirmed by PCR test.
• Staff members with present or past SARS-CoV-2 infection, or with PCR-confirmed symptoms consistent with COVID19.
• History of QT interval prolongation or arrhythmias of any etiology.
• Presence of retinopathy of any etiology, changes in acuity or visual field.
• Severe hearing loss (requires the use of hearing aids).
• Structural heart disease.
• History of non-structural heart failure, ischemic heart disease, SCASEST, or SCACEST
• Chronic liver disease.
• Alcoholism.
• Epilepsy.
• For the participating professionals, pregnancy or suspected pregnancy (if they are planning pregnancy, or in fertilizer treatment, they must abandon the study).
• Subjects with known HDQ hypersensitivity.
• Subjects diagnosed with G6PDH deficiency.
• Taking other medicines that prolong QT: domperidone, ondansetron, cilostazol, antiarrhythmics (procainamide, amiodarone, flecainide, sotalol), macrolides (azithromycin, clarithromycin, erythromycin), quinolones (ciprofloxacin,), moxofloxacin,) neuroleptics (haloperidol, chlorpromazine, pimozide), antidepressants (citalopram, escitalopram), sulpiride, anticholinesterase drugs (donepezil)
• Denial to participate in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Instituto de Investigacion Biomedica de Malaga

OTHER

Sponsor Role: collaborator

Carlos III Health Institute

OTHER_GOV

Sponsor Role: collaborator

University of Malaga

OTHER

Sponsor Role: lead

Responsible Party

JOSE MIGUEL MORALES ASENCIO

Professor of Research Methods and Evidence Based Health Care at University of Málaga (Spain)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

José M Morales-Asencio, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Malaga; Malaga, Spain.

Ricardo Gómez-Huelgas, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Regional de Malaga

Juan C Morilla-Herrera, PhD

Role: PRINCIPAL_INVESTIGATOR

Distrito de Atención Primaria Málaga-Valle del Guadalhorce

Central Contacts

José M Morales-Asencio, Professor

Role: CONTACT

jmmasen@uma.es

+34 629 77 68 95

References

Ganyani T, Kremer C, Chen D, Torneri A, Faes C, Wallinga J, Hens N. Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020. Euro Surveill. 2020 Apr;25(17):2000257. doi: 10.2807/1560-7917.ES.2020.25.17.2000257.

Reference Type: BACKGROUND

PMID: 32372755 (View on PubMed)

Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis. 2020 Apr;20(4):411-412. doi: 10.1016/S1473-3099(20)30113-4. Epub 2020 Feb 24. No abstract available.

Reference Type: BACKGROUND

PMID: 32105638 (View on PubMed)

Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19. No abstract available.

Reference Type: BACKGROUND

PMID: 32074444 (View on PubMed)

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 May 5;172(9):577-582. doi: 10.7326/M20-0504. Epub 2020 Mar 10.

Reference Type: BACKGROUND

PMID: 32150748 (View on PubMed)

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

Reference Type: BACKGROUND

PMID: 32187464 (View on PubMed)

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

Reference Type: BACKGROUND

PMID: 32020029 (View on PubMed)

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.

Reference Type: BACKGROUND

PMID: 32205204 (View on PubMed)

Yan Y, Zou Z, Sun Y, Li X, Xu KF, Wei Y, Jin N, Jiang C. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013 Feb;23(2):300-2. doi: 10.1038/cr.2012.165. Epub 2012 Dec 4. No abstract available.

Reference Type: BACKGROUND

PMID: 23208422 (View on PubMed)

Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 2006 Feb;6(2):67-9. doi: 10.1016/S1473-3099(06)70361-9. No abstract available.

Reference Type: BACKGROUND

PMID: 16439323 (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)

Shipman WD, Vernice NA, Demetres M, Jorizzo JL. An update on the use of hydroxychloroquine in cutaneous lupus erythematosus: A systematic review. J Am Acad Dermatol. 2020 Mar;82(3):709-722. doi: 10.1016/j.jaad.2019.07.027. Epub 2019 Jul 13.

Reference Type: BACKGROUND

PMID: 31306730 (View on PubMed)

multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009. Chinese.

Reference Type: BACKGROUND

PMID: 32164085 (View on PubMed)

Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC Med Res Methodol. 2006 Nov 8;6:54. doi: 10.1186/1471-2288-6-54.

Reference Type: BACKGROUND

PMID: 17092344 (View on PubMed)

McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, Lewis J, Baer A, Kawakami V, Lukoff MD, Ferro J, Brostrom-Smith C, Rea TD, Sayre MR, Riedo FX, Russell D, Hiatt B, Montgomery P, Rao AK, Chow EJ, Tobolowsky F, Hughes MJ, Bardossy AC, Oakley LP, Jacobs JR, Stone ND, Reddy SC, Jernigan JA, Honein MA, Clark TA, Duchin JS; Public Health-Seattle and King County, EvergreenHealth, and CDC COVID-19 Investigation Team. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. N Engl J Med. 2020 May 21;382(21):2005-2011. doi: 10.1056/NEJMoa2005412. Epub 2020 Mar 27.

Reference Type: BACKGROUND

PMID: 32220208 (View on PubMed)

Kimball A, Hatfield KM, Arons M, James A, Taylor J, Spicer K, Bardossy AC, Oakley LP, Tanwar S, Chisty Z, Bell JM, Methner M, Harney J, Jacobs JR, Carlson CM, McLaughlin HP, Stone N, Clark S, Brostrom-Smith C, Page LC, Kay M, Lewis J, Russell D, Hiatt B, Gant J, Duchin JS, Clark TA, Honein MA, Reddy SC, Jernigan JA; Public Health - Seattle & King County; CDC COVID-19 Investigation Team. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):377-381. doi: 10.15585/mmwr.mm6913e1.

Reference Type: BACKGROUND

PMID: 32240128 (View on PubMed)

Quagliarello V, Ginter S, Han L, Van Ness P, Allore H, Tinetti M. Modifiable risk factors for nursing home-acquired pneumonia. Clin Infect Dis. 2005 Jan 1;40(1):1-6. doi: 10.1086/426023. Epub 2004 Dec 1.

Reference Type: BACKGROUND

PMID: 15614684 (View on PubMed)

Chesney MA, Ickovics JR, Chambers DB, Gifford AL, Neidig J, Zwickl B, Wu AW. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. Patient Care Committee & Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical Trials Group (AACTG). AIDS Care. 2000 Jun;12(3):255-66. doi: 10.1080/09540120050042891.

Reference Type: BACKGROUND

PMID: 10928201 (View on PubMed)

Pagarolas AA, Sune TP. [Microbiological diagnosis of viral respiratory infections in the adult patient]. Enferm Infecc Microbiol Clin. 2014 Feb;32 Suppl 1:51-6. doi: 10.1016/S0213-005X(14)70150-8. Spanish.

Reference Type: BACKGROUND

PMID: 24630584 (View on PubMed)

Kalil AC. Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics. JAMA. 2020 May 19;323(19):1897-1898. doi: 10.1001/jama.2020.4742. No abstract available.

Reference Type: BACKGROUND

PMID: 32208486 (View on PubMed)

Related Links

https://www.segg.es/media/descargas/pautas-SEGG-covid-19.pdf

Sociedad Española de Geriatría y Gerontología. Colaboración servicios de geriatría hospitalarios - hospitales de media estancia - residencias de mayores y centros sociosanitarios. 2020

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000890-25/FR

Mitja O. Antiviral Treatment of COVID-19 Confirmed Cases and Ring Chloroquine Chemoprevention in Close Contacts: a Cluster Randomized Clinical Trial. 2020 \[cited 2020 Mar 22\]. (Clinical Trials.gov). Report No.: NCT04304053.

Other Identifiers

COV20/00565

Identifier Type: -

Identifier Source: org_study_id