Clinical trial NCT04627467: Prevention With Chloroquine in Health Personnel Exposed to Infection With Coronavirus Disease 2019 (COVID-19) (TS-COVID)
Official title: Prophylaxis With Chloroquine in Health Personnel Exposed to Infection With Coronavirus Disease 2019 (COVID-19)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: Chloroquine
COVID-19
SARS-CoV-2
Antibodies
Prophylaxis
Healthcare workers
Lead sponsor: Fundacion Clinica Valle del Lili
Sponsor class: OTHER
First posted: 2020-11-13
Enrollment: 3217
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm study in which healthcare workers were actively invited to participate. After verifying volunteer's eligibility through a survey that evaluated the presence of COVID-19 symptoms (primary efficacy outcome), 150 mg chloroquine base was dispensed in site by a pharmaceutical chemist at days 0, 15, 30, 45, 60, and 75. Questions regarding adverse drugs reactions (safety outcome) were included in the survey after the first dose was administered. Participants who discontinued chloroquine were followed up until study completion.
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the efficacy and safety of chloroquine prophylaxis on the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in healthcare workers exposed to patients with confirmed Coronavirus Disease 2019 (COVID-19)

Detailed description: Single arm study in which healthcare workers were actively invited to participate. Possible participants were asked to complete a questionnaire to determine eligibility for study entry and to identify risk factors for infection, severe infection, or adverse events associated with chloroquine use.

Volunteers who meet the eligibility requirements received chloroquine 150mg base at days 0, 15, 30, 45, 60, 75. Cumulative incidence and incidence rate of COVID-19 at days 30,60 and 90 were calculated. Presence of Immunoglobulin G (IgG) antibodies against SARS-Cov-2 was evaluated at the beginning, at the end and at any moment if they become infected with this virus.

In addition, patients were asked to complete a survey evaluating adverse effects and COVID-19 symptoms at day 0 and weeks 2,4,6,8,10, and 12.

Eligibility criteria: Inclusion Criteria:

* Asymptomatic healthcare workers and contractors who work in Fundacion Valle del Lili

Exclusion Criteria:

* To have two or more of the following symptoms 14 days previous to the initial assessment: cough, dyspnea, odynophagia, fatigue, weakness, fever \>38 degrees °C
* History of close contact (less than two meters) with a person with probable or confirmed COVID-19 without adequate protection during the last 14 days
* History of one the following diseases in treatment at inclusion in the study: cardiac arrhythmias, epilepsy, kidney disease, seizures
* Treatment with concomitant medications: tamoxifen, quinine, cyclosporine, amiodarone, digoxine, anticonvulsivants
* Having recently taken chloroquine or hydroxychloroquine in the last two weeks
* Known hypersensitivity to chloroquine or hydroxychloroquine

Primary outcomes:
measure: COVID-19 infection
timeFrame: Day 15
measure: COVID-19 infection
timeFrame: Day 30
measure: COVID-19 infection
timeFrame: Day 45
measure: COVID-19 infection
timeFrame: Day 60
measure: COVID-19 infection
timeFrame: Day 75
measure: COVID-19 infection
timeFrame: Day 90
Secondary outcomes:
measure: IgG antibodies seropositivity against SARS-CoV-2
timeFrame: Day 90
Other outcomes:
measure: Adverse drug event
timeFrame: Day 15, day 30, day 45, day 60, day 75 and day 90
measure: Unexpected adverse events
timeFrame: Day 15, day 30, day 45, day 60, day 75 and day 90
measure: Participant drop-out
timeFrame: Baseline and day 90
measure: Non-adherence
timeFrame: Baseline and day 90
Locations:
city: Cali
country: Colombia
facility: Fundacion Valle del Lili
state: Valle Del Cauca
Study officials:
affiliation: Fundacion Clinica Valle del Lili
name: Juan D Velez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: WHO. Coronavirus disease 2019 (COVID-19). Situation Report - 43 2020 [Available from: https://www.who.int/emergencies/diseases/novel-coronavirus2019/technicalguidance/laboratoryguidance
citation: Wang M, Su S, Lv J, Zhou G, Wang Q, Guo C. Analysis of clinical features and prognostic factors in Chinese patients with rheumatic diseases in an intensive care unit. The Egyptian Rheumatologist. 2018;40(1):63-6.
citation: Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020 Apr 14;323(14):1335. doi: 10.1001/jama.2020.4344. No abstract available.
citation: 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.
citation: 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.
citation: Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Jul 1;75(7):1667-1670. doi: 10.1093/jac/dkaa114.
citation: Rodriguez-Morales AJ, Cardona-Ospina JA, Gutierrez-Ocampo E, Villamizar-Pena R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C, Henao-Martinez AF, Paniz-Mondolfi A, Lagos-Grisales GJ, Ramirez-Vallejo E, Suarez JA, Zambrano LI, Villamil-Gomez WE, Balbin-Ramon GJ, Rabaan AA, Harapan H, Dhama K, Nishiura H, Kataoka H, Ahmad T, Sah R; Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19). Electronic address: https://www.lancovid.org. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 Mar-Apr;34:101623. doi: 10.1016/j.tmaid.2020.101623. Epub 2020 Mar 13.
citation: Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D, Chen B, Zhang Z, Guan W, Ling Z, Jiang R, Hu T, Ding Y, Lin L, Gan Q, Luo L, Tang X, Liu J. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020 May;47(5):1275-1280. doi: 10.1007/s00259-020-04735-9. Epub 2020 Feb 28.
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
citation: Gostic K, Gomez AC, Mummah RO, Kucharski AJ, Lloyd-Smith JO. Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19. Elife. 2020 Feb 24;9:e55570. doi: 10.7554/eLife.55570.
citation: Chowell G, Abdirizak F, Lee S, Lee J, Jung E, Nishiura H, Viboud C. Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study. BMC Med. 2015 Sep 3;13:210. doi: 10.1186/s12916-015-0450-0.
citation: Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):145-151. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003. Chinese.
citation: Su A. Doctors and nurses fighting coronavirus in China die of both infection and fatigue. Los Angeles Times. 2020.
citation: Liu M, He P, Liu HG, Wang XJ, Li FJ, Chen S, Lin J, Chen P, Liu JH, Li CH. [Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Feb 17;43(0):E016. doi: 10.3760/cma.j.issn.1001-0939.2020.0016. Online ahead of print. Chinese.
citation: Mitja O, Clotet B. Use of antiviral drugs to reduce COVID-19 transmission. Lancet Glob Health. 2020 May;8(5):e639-e640. doi: 10.1016/S2214-109X(20)30114-5. Epub 2020 Mar 19. No abstract available.
citation: Welliver R, Monto AS, Carewicz O, Schatteman E, Hassman M, Hedrick J, Jackson HC, Huson L, Ward P, Oxford JS; Oseltamivir Post Exposure Prophylaxis Investigator Group. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001 Feb 14;285(6):748-54. doi: 10.1001/jama.285.6.748.
citation: Hydroxychloroquine Chemoprophylaxis in Healthcare Personnel in Contact With COVID-19 Patients (PHYDRA Trial) - Full Text View. ClinicalTrials.gov.
citation: Chloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting - Full Text View. ClinicalTrials.gov
citation: Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention - Full Text View. ClinicalTrials.gov
citation: Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010 Jan;69(1):20-8. doi: 10.1136/ard.2008.101766.
citation: Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol. 2011 Apr 15;186(8):4794-804. doi: 10.4049/jimmunol.1000702. Epub 2011 Mar 11.
citation: Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7. doi: 10.1016/s1473-3099(03)00806-5.
citation: 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.
citation: IDOATE A, IDOIPE Á. 2.4. Investigación y ensayos clínicos.
citation: Schwartz E. Prophylaxis of malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012045. doi: 10.4084/MJHID.2012.45. Epub 2012 Jun 29.
citation: Gozal D, Hengy C, Fadat G. Prolonged malaria prophylaxis with chloroquine and proguanil (chloroguanide) in a nonimmune resident population of an endemic area with a high prevalence of chloroquine resistance. Antimicrob Agents Chemother. 1991 Feb;35(2):373-6. doi: 10.1128/AAC.35.2.373.
citation: 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.
citation: Chen W, Huang Y. To Protect Health Care Workers Better, To Save More Lives With COVID-19. Anesth Analg. 2020 Jul;131(1):97-101. doi: 10.1213/ANE.0000000000004834.