Clinical trial NCT04328493: The Vietnam Chloroquine Treatment on COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV-2 Infection
COVID-19
Keywords: SARS-CoV-2
COVID-19
chloroquine
Lead sponsor: Oxford University Clinical Research Unit, Vietnam
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Vietnam
name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
name: Cu Chi COVID Hospital, Vietnam
name: Can Gio COVID Hospital, Vietnam
name: Cho Ray Hospital
name: National Hospital for Tropical Diseases, Hanoi, Vietnam
name: Department of Health, Ho Chi Minh city
First posted: 2020-03-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The main trial is an open label, randomised, controlled trial that will be conducted in in-patients in Ho Chi Minh City. Viet Nam. Randomization will be 1:1, stratified by study site and severity of illness, to either with or without chloroquine for 10 days. All patients will also receive a supportive care/treatment according to VN MoH's guideline for COVID-19
Primary purpose: TREATMENT

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.

Eligibility criteria: 1. 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.
2. Provides written informed consent prior to initiation of any study procedures (or legally authorized representative).
3. Understands and agrees to comply with planned study procedures.
4. Agrees to the collection of OP swabs and venous blood per protocol.
5. Male or female adult ≥18 years of age at time of enrollment.

Primary outcomes:
measure: Viral clearance time
timeFrame: Up to 56 days post randomization
Secondary outcomes:
measure: Length of hospital stay
timeFrame: Up to 56 days post randomization
measure: Ventilator free days
timeFrame: first 28 days
measure: Oxygen free days
timeFrame: first 28 days
measure: Time to death
timeFrame: first 7, 10, 14, 28 and 56 days since randomization
measure: Adverse events
timeFrame: Over the first 28 days (due to the prolonged half-life of Chloroquine)
measure: fever clearance time
timeFrame: Up to 56 days post randomization
measure: Ordinal outcome scale
timeFrame: Up to 56 days post randomization
measure: Development of ARDS
timeFrame: Up to 56 days post randomization
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: National Hospital for Tropical Diseases
city: Ho Chi Minh City
country: Vietnam
facility: Can Gio COVID Hospital
city: Ho Chi Minh City
country: Vietnam
facility: Cho Ray Hospital
city: Ho Chi Minh City
country: Vietnam
facility: Cu Chi COVID Hospital
city: Ho Chi Minh City
country: Vietnam
facility: Hospital for Tropical Diseases
Study officials:
affiliation: University of Oxford, UK
name: Guy Thwaites, PhD. MD
role: PRINCIPAL_INVESTIGATOR
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