- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04328493
The Vietnam Chloroquine Treatment on COVID-19 (VICO)
A Multi Center Randomized Open Label Trial on the Safety and Efficacy of Chloroquine for the Treatment of Hospitalized Adults With Laboratory Confirmed SARS-CoV-2 Infection in Vietnam
COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate potential therapeutics for the treatment of hospitalized COVID-19.
We hypothesis that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid declines in viral load in throat swabs. This viral attenuation should be associated with improved patient outcomes. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19.
The study is funded and leaded by The Ministry of Health, Vietnam.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study will start with a 10-patient prospective observational pilot study. All these patients will be subject to the same entry and exclusion criteria for the randomized trial, and undergo the same procedures. They will all receive chloroquine at the doses used in the trial (see sections below); they will not be randomized. The purpose of the pilot is to develop the study procedures for the randomized controlled trial, including the safe monitoring of patients, to refine the CRF, and to acquire some preliminary data on the safety of chloroquine in those with COVID-19.
Once the pilot study has been completed, and the data reviewed by the TSC and DMC, and the MOH ethics committee, we will then proceed to the trial. We will aim for minimum delay between completing the pilot study and starting the randomized trial.
The main study is an open label, randomised, controlled trial that will be conducted in 240 in-patients in Ho Chi Minh City. Viet Nam.
Patients will have daily assessment as per standard of care while in-patients by the hospital staff. While in-patients the study will collect the following data: peripheral oxygen saturation (pulse oximeter), respiratory rate, and FiO2. These will be recorded between 2 and 4 times per day depending on the practice of the treating site. Where recording is twice daily, one record will be made from the time period of 00:00 until 12:00, and the second recording between 12:01 and 23:59. Where the parameters are recorded four times/day they will be recorded in each of the time periods 00:00 - 06:00, 06:01 - 12:00, 12:01 - 18:00 and 18:01 - 23:59. Vitals recorded will include: FiO2, SpO2, Temp, RR HR BP. The use of ventilator or other assisted breathing device will be recorded each day.
Patients will have clinical assessment recorded as per the study schedule.
The decision to discharge patients will be at the discretion of the attending physician and depend upon the clinical status of the patient. According to current standard of care recovery and hospital discharge is dependent upon the patient having had 2 daily consecutive negative PCR throat/nose swabs. Following discharge patients will be seen on days 14, 28, 42 and 56 post-randomization.
In a subset of patients admitted to HTD we will look for ECG changes, using real-time monitoring.
Patients will have up to 1 hour ECG continuous recordings daily. The ECG recording will be downloaded from standard monitor (GE Careview) and stored electronically. ECG changes (including QT interval) will then be analyzed by machine learning.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Hanoi, Vietnam
- National Hospital for Tropical Diseases
-
Ho Chi Minh City, Vietnam
- Hospital for Tropical Diseases
-
Ho Chi Minh City, Vietnam
- Can Gio COVID Hospital
-
Ho Chi Minh City, Vietnam
- Cho Ray Hospital
-
Ho Chi Minh City, Vietnam
- Cu Chi COVID Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 48 hours prior to randomization, and requiring hospital admission in the opinion of the attending physician.
- Provides written informed consent prior to initiation of any study procedures (or legally authorized representative).
- Understands and agrees to comply with planned study procedures.
- Agrees to the collection of OP swabs and venous blood per protocol.
- Male or female adult ≥18 years of age at time of enrollment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control arm
Patients randomized to the control arm will receive a standard of care therapy (a supportive care/treatment according to VN MoH's guideline).
|
|
Experimental: Intervention arm
In addition to standard of care therapy, patients randomized to the intervention arm receive chloroquine phosphate as below. For adult ≥ 53kg: 1000mg (4 tablets) at initial dose (T=0), followed by 500mg (2 tablets) at 6 hours later (T=6), and 500mg (2 tablets) once daily for 9 days. For adult from 45 - 52kg: 875mg (3.5 tablets) at T=0, followed by 500mg (2 tablets) at T=6 and 500mg (2 tablets) once daily thereafter. For adult weighted 38 -<45 kg: 750mg (3 tablets) at T=0, followed by 375mg (1.5 tablets) at T = 6 and 375mg (1.5 tablets) once daily thereafter. For adult weighted <38 kg: 625mg (2.5 tablets) at T=0, followed by 375mg (1.5 tablets) at T=6 and 375mg (1.5 tablets) once daily thereafter. The total duration of treatment with chloroquine will be 10 days. |
Each chloroquine tablet contains 250mg chloroquine phosphate (or 150mg chloroquine base). Chloroquine treatment for patient is weight-based dosing. Chloroquine will be administered orally, as tablets. For unconscious patients chloroquine can be crushed and administered as a suspension via a nasogastric tube. The total duration of treatment with Chloroquine will be 10 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Viral clearance time
Time Frame: Up to 56 days post randomization
|
Viral presence will be determined using RT-PCR to detect SARS-CoV-19 RNA.
Throat/nose swabs for viral RNA will be taken daily while in hospital until there have at least 2 consecutive negative results .
Virus will be defined as cleared when the patient has had ≥2 consecutive negative PCR tests.
The time to viral clearance will be defined as the time following randomization to the first of the negative throat/nose swabs.
|
Up to 56 days post randomization
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Length of hospital stay
Time Frame: Up to 56 days post randomization
|
The time since randomization to discharge between study groups
|
Up to 56 days post randomization
|
Ventilator free days
Time Frame: first 28 days
|
The number of ventilator free days over the first 28 days of treatment
|
first 28 days
|
Oxygen free days
Time Frame: first 28 days
|
The number of oxygen free days over the first 28 days of treatment
|
first 28 days
|
Time to death
Time Frame: first 7, 10, 14, 28 and 56 days since randomization
|
The time to (all-cause) death following over the first 7, 10, 14, 28 and 56 days since randomization
|
first 7, 10, 14, 28 and 56 days since randomization
|
Adverse events
Time Frame: Over the first 28 days (due to the prolonged half-life of Chloroquine)
|
The rates of serious adverse events, rates of grade 3 or 4 adverse events
|
Over the first 28 days (due to the prolonged half-life of Chloroquine)
|
fever clearance time
Time Frame: Up to 56 days post randomization
|
Time since randomization to the first defervescence day
|
Up to 56 days post randomization
|
Ordinal outcome scale
Time Frame: Up to 56 days post randomization
|
WHO Ordinal outcome scale for COVID-19
|
Up to 56 days post randomization
|
Development of ARDS
Time Frame: Up to 56 days post randomization
|
Development of ARDS defined by the Kigali criteria
|
Up to 56 days post randomization
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Guy Thwaites, PhD. MD, University of Oxford, UK
Publications and helpful links
General Publications
- Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
- 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.
- Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.
- de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. doi: 10.1073/pnas.1922083117. Epub 2020 Feb 13.
- Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.
- Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Gotte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem. 2020 Apr 10;295(15):4773-4779. doi: 10.1074/jbc.AC120.013056. Epub 2020 Feb 24.
- Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012 Nov 8;367(19):1814-20. doi: 10.1056/NEJMoa1211721. Epub 2012 Oct 17. Erratum In: N Engl J Med. 2013 Jul 25;369(4):394.
- 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.
- Biggerstaff M, Cauchemez S, Reed C, Gambhir M, Finelli L. Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature. BMC Infect Dis. 2014 Sep 4;14:480. doi: 10.1186/1471-2334-14-480.
- Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020 Jan 28;9(1):221-236. doi: 10.1080/22221751.2020.1719902. eCollection 2020. Erratum In: Emerg Microbes Infect. 2020 Dec;9(1):540.
- Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018 Dec;14(12):693-703. doi: 10.1038/s41584-018-0111-8.
- 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 Mar 12;43(3):209-214. doi: 10.3760/cma.j.issn.1001-0939.2020.03.014. Chinese.
- McChesney EW, Banks WF Jr, Fabian RJ. Tissue distribution of chloroquine, hydroxychloroquine, and desethylchloroquine in the rat. Toxicol Appl Pharmacol. 1967 May;10(3):501-13. doi: 10.1016/0041-008x(67)90089-0. No abstract available.
- Shaw K. The 2003 SARS outbreak and its impact on infection control practices. Public Health. 2006 Jan;120(1):8-14. doi: 10.1016/j.puhe.2005.10.002. Epub 2005 Nov 16.
- Villegas L, McGready R, Htway M, Paw MK, Pimanpanarak M, Arunjerdja R, Viladpai-Nguen SJ, Greenwood B, White NJ, Nosten F. Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double-blind, placebo-controlled trial. Trop Med Int Health. 2007 Feb;12(2):209-18. doi: 10.1111/j.1365-3156.2006.01778.x.
- Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69. doi: 10.1186/1743-422X-2-69.
- White NJ, Miller KD, Churchill FC, Berry C, Brown J, Williams SB, Greenwood BM. Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988 Dec 8;319(23):1493-500. doi: 10.1056/NEJM198812083192301.
- Zhao S, Lin Q, Ran J, Musa SS, Yang G, Wang W, Lou Y, Gao D, Yang L, He D, Wang MH. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak. Int J Infect Dis. 2020 Mar;92:214-217. doi: 10.1016/j.ijid.2020.01.050. Epub 2020 Jan 30.
- Kestelyn E, Dung NTP, Lam Minh Y, Hung LM, Quan NM, Dung NT, Minh NNQ, Xuan TC, Phong NT, Ninh Thi Thanh V, Donovan J, Tu TNH, Nhat LTH, Truong NT, Man DNH, Thao HP, Ngoc NM, Lam VT, Phat HH, Phuong PM, Geskus RB, Ha VTN, Quang NN, Tran Tinh H, Tan LV, Thwaites GE, Day JN, Chau NVV; OUCRU COVID-19 Research Group. A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam. Wellcome Open Res. 2020 Jun 12;5:141. doi: 10.12688/wellcomeopenres.15936.1. eCollection 2020.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Infections
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Amebicides
- Filaricides
- Antinematodal Agents
- Anthelmintics
- Chloroquine
- Chloroquine diphosphate
Other Study ID Numbers
- COVID
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on COVID-19
-
University of Roma La SapienzaQueen Mary University of London; Università degli studi di Roma Foro Italico; Bios Prevention SrlCompletedPost Acute Sequelae of COVID-19 | Post COVID-19 Condition | Long-COVID | Chronic COVID-19 SyndromeItaly
-
Yang I. PachankisActive, not recruitingCOVID-19 Respiratory Infection | COVID-19 Stress Syndrome | COVID-19 Vaccine Adverse Reaction | COVID-19-Associated Thromboembolism | COVID-19 Post-Intensive Care Syndrome | COVID-19-Associated StrokeChina
-
Massachusetts General HospitalRecruitingPost Acute COVID-19 Syndrome | Long COVID | Post Acute Sequelae of COVID-19 | Long COVID-19United States
-
Indonesia UniversityRecruitingPost-COVID-19 Syndrome | Long COVID | Post COVID-19 Condition | Post-COVID Syndrome | Long COVID-19Indonesia
-
Erasmus Medical CenterDa Vinci Clinic; HGC RijswijkNot yet recruitingPost-COVID-19 Syndrome | Long COVID | Long Covid19 | Post COVID-19 Condition | Post-COVID Syndrome | Post COVID-19 Condition, Unspecified | Post-COVID ConditionNetherlands
-
Dr. Soetomo General HospitalIndonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, IndonesiaRecruitingCOVID-19 Pandemic | COVID-19 Vaccines | COVID-19 Virus DiseaseIndonesia
-
University of Witten/HerdeckeInstitut für Rehabilitationsforschung NorderneyCompletedPost-COVID-19 Syndrome | Long-COVID-19 SyndromeGermany
-
Jonathann Kuo, MDActive, not recruitingSARS-CoV2 Infection | Post-COVID-19 Syndrome | Dysautonomia | Post Acute COVID-19 Syndrome | Long COVID | Long Covid19 | COVID-19 Recurrent | Post-Acute COVID-19 | Post-Acute COVID-19 Infection | Post Acute Sequelae of COVID-19 | Dysautonomia Like Disorder | Dysautonomia Orthostatic Hypotension Syndrome | Post... and other conditionsUnited States
-
University Hospital, Ioannina1st Division of Internal Medicine, University Hospital of IoanninaRecruitingCOVID-19 Pneumonia | COVID-19 Respiratory Infection | COVID-19 Pandemic | COVID-19 Acute Respiratory Distress Syndrome | COVID-19-Associated Pneumonia | COVID 19 Associated Coagulopathy | COVID-19 (Coronavirus Disease 2019) | COVID-19-Associated ThromboembolismGreece
Clinical Trials on Chloroquine phosphate
-
Dinka DugassaEthiopian Public Health InstituteCompletedMalaria | Efficacy | Vivax Malaria | ChloroquineEthiopia
-
Centro de Investigação em Saúde de ManhiçaCompleted
-
National University Hospital, SingaporeUnknown
-
University of South FloridaRecruitingAtrial FibrillationUnited States
-
LILIA GONZALEZ CERONPan American Health Organization; Instituto de Diagnóstico y Referencia Epidemiológicos... and other collaboratorsCompleted
-
Wroclaw Medical UniversityCompleted
-
CMN "20 de Noviembre"Unknown
-
University of MinnesotaMinnesota Medical FoundationTerminatedHIV InfectionsUnited States
-
Asan Medical CenterCompletedHealthy VolunteersKorea, Republic of
-
Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories...AHEPA University Hospital; Sismanoglio General Hospital; Athens General Hospital... and other collaboratorsTerminated