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The Vietnam Chloroquine Treatment on COVID-19

Phase 2
Completed
Conditions
COVID-19
SARS-CoV-2 Infection
Interventions
Registration Number
NCT04328493
Lead Sponsor
Oxford University Clinical Research Unit, Vietnam
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intervention armChloroquine phosphateIn 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.
Primary Outcome Measures
NameTimeMethod
Viral clearance timeUp 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.

Secondary Outcome Measures
NameTimeMethod
fever clearance timeUp to 56 days post randomization

Time since randomization to the first defervescence day

Time to deathfirst 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

Adverse eventsOver 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

Ordinal outcome scaleUp to 56 days post randomization

WHO Ordinal outcome scale for COVID-19

Development of ARDSUp to 56 days post randomization

Development of ARDS defined by the Kigali criteria

Length of hospital stayUp to 56 days post randomization

The time since randomization to discharge between study groups

Ventilator free daysfirst 28 days

The number of ventilator free days over the first 28 days of treatment

Oxygen free daysfirst 28 days

The number of oxygen free days over the first 28 days of treatment

Trial Locations

Locations (5)

Cho Ray Hospital

🇻🇳

Ho Chi Minh City, Vietnam

Cu Chi COVID Hospital

🇻🇳

Ho Chi Minh City, Vietnam

Can Gio COVID Hospital

🇻🇳

Ho Chi Minh City, Vietnam

National Hospital for Tropical Diseases

🇻🇳

Hanoi, Vietnam

Hospital for Tropical Diseases

🇻🇳

Ho Chi Minh City, Vietnam

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