Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection

NCT04341727 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 202003188
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring intensive care unit (ICU) admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.

Conditions

Coronavirus Infection

Outcome Measures

Primary Outcomes (1)

• Hours to Recovery

  Time (hours) from randomization to recovery defined as 1) absence of fever, as defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications AND 2) absence of symptoms of greater than mild severity for 24 hours AND 3) not requiring supplemental oxygen beyond pre-COVID baseline AND 4) freedom from mechanical ventilation or death in each Arm/Group,respectively.

  42 days

Secondary Outcomes (1)

• Time to Fever Resolution

  42 days

Study Arms (4)

Hydroxychloroquine alone

ACTIVE COMPARATOR

Arm 1: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets.

Drug: Hydroxychloroquine Sulfate

Hydroxychloroquine plus azithromycin

ACTIVE COMPARATOR

Arm 2: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets. AND Azithromycin 500mg orally once, followed by 250mg daily for four consecutive days (five days total). The drug will be supplied in 250mg tablets.

Drug: Hydroxychloroquine Sulfate; Drug: Azithromycin

Chloroquine alone

ACTIVE COMPARATOR

Arm 3: Chloroquine phosphate 1000mg orally once, followed in 12 hours by 500mg, then 500mg orally twice daily for 4 days (Five days in total). The drug will be supplied in 500mg tablets.

Drug: Chloroquine Sulfate

Chloroquine plus azithromycin

ACTIVE COMPARATOR

Arm 4: Chloroquine phosphate 1000mg orally once, followed in 12 hours by 500mg, then 500mg orally twice daily for 4 days (Five days in total). The drug will be supplied in 500mg tablets. AND Azithromycin 500mg orally once, followed by 250mg daily for 4 consecutive days (5 days total).The drug will be supplied in 250mg tablets.

Drug: Azithromycin; Drug: Chloroquine Sulfate

Interventions

Hydroxychloroquine Sulfate DRUG

anti-rheumatic drug (DMARD)

Also known as: HYDROXYCHLOROQUINE Plaquenil

Hydroxychloroquine alone; Hydroxychloroquine plus azithromycin

Azithromycin DRUG

Antibiotic

Also known as: COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin

Chloroquine plus azithromycin; Hydroxychloroquine plus azithromycin

Chloroquine Sulfate DRUG

Antimalarial

Also known as: Aralen GENERIC NAME(S): Chloroquine Phosphate

Chloroquine alone; Chloroquine plus azithromycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalization for management of SARS CoV-2 infection
• Positive SARS CoV-2 test
• Age \>=18 years
• Provision of informed consent
• Electrocardiogram (ECG) ≤48 hours prior to enrollment
• Complete blood count, glucose-6 phosphate-dehydrogenase (G6PD), comprehensive metabolic panel and magnesium ≤48 hours prior to enrollment from standard of care.
• If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study. At least one of the following must be used throughout the study:
• Condom (male or female) with or without spermicide
• Diaphragm or cervical cap with spermicide
• Intrauterine device (IUD)
• Hormone-based contraceptive

You may not qualify if:

• Contraindication or allergy to chloroquine, hydroxychloroquine or azithromycin
• Current use hydroxychloroquine, chloroquine or azithromycin
• Concurrent use of another investigational agent
• Invasive mechanical ventilation
• Participants who have any severe and/or uncontrolled medical conditions such as:
• unstable angina pectoris,
• symptomatic congestive heart failure,
• myocardial infarction,
• cardiac arrhythmias or know prolonged QTc \>470 males, \>480 female on ECG
• pulmonary insufficiency,
• epilepsy (interaction with chloroquine),
• Prior retinal eye disease
• Concurrent malignancy requiring chemotherapy
• Known Chronic Kidney disease, eGFR\<10 or dialysis
• G-6-PD deficiency, if unknown requires G6PD testing prior to enrollment

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (2)

Washington University School of Medicine Infectious Disease Clinical Research Unit

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Coronavirus Infections

Interventions

Hydroxychloroquine; Azithromycin; Chloroquine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

Enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.

Results Point of Contact

• Title: Jane O'Halloran
• Organization: Washington University School of Medicine

janeohalloran@wustl.edu

314 454 0058

Study Officials

• Jane O'Halloran, MD PhD

  Washington University School of Medicine (ID-CRU)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Medicine

Study Record Dates

• First Submitted: April 4, 2020
• First Posted: April 10, 2020
• Study Start: April 4, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: April 25, 2024
• Results First Posted: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)