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Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352)

Primary Purpose

Coronavirus Infection

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine Sulfate
Azithromycin
Chloroquine Sulfate
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

    • Known Porphyria
    • Known myasthenia gravis
    • Currently pregnant or planning on getting pregnant while on study
    • Breast feeding
    • AST/ALT >five times the upper limit of normal ULN*
    • Bilirubin >five times the ULN*
    • Magnesium <1.4 mEq/L*
    • Calcium <8.4mg/dL >10.6mg/dL*
    • Potassium <3.3 >5.5 mEg/L*

Sites / Locations

  • Washington University School of Medicine Infectious Disease Clinical Research Unit
  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Hydroxychloroquine alone

Hydroxychloroquine plus azithromycin

Chloroquine alone

Chloroquine plus azithromycin

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time fever resolution
Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications

Full Information

First Posted
April 4, 2020
Last Updated
October 5, 2021
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04341727
Brief Title
Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection
Acronym
WU352
Official Title
WU 352: Open-label, Randomized Controlled Trial of Hydroxychloroquine Alone or Hydroxychloroquine Plus Azithromycin or Chloroquine Alone or Chloroquine Plus Azithromycin in the Treatment of SARS CoV-2 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
DSMB recommended study suspension slow accrual
Study Start Date
April 4, 2020 (Actual)
Primary Completion Date
April 1, 2021 (Actual)
Study Completion Date
April 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.
Detailed Description
This Phase III trial will utilize four treatment strategies in non-critically ill hospitalized participants (not requiring mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin. Investigators are primarily interested in the time to recovery. In addition to study medications there will be daily symptom surveys for 14 days, then weekly thereafter for 4 weeks resulting in a total duration of follow up of 42 days. During hospitalization, daily symptom surveys will be completed in conjunction withthe study coordinators. On discharge participants will have the option to complete electronic symptom surveys or complete symptom surveys via telephone with study coordinator. In the event that the participant opts for electronic symptom surveys on discharge participants will in addition receive a follow up call from a study coordination every 7 days during the initial 14 day period. In addition, failure to submit a symptom survey will prompt a study follow up call. Data from SOC will be collected from medical records.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine alone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Hydroxychloroquine plus azithromycin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Chloroquine alone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Chloroquine plus azithromycin
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate
Other Intervention Name(s)
HYDROXYCHLOROQUINE Plaquenil
Intervention Description
anti-rheumatic drug (DMARD)
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin
Intervention Description
Antibiotic
Intervention Type
Drug
Intervention Name(s)
Chloroquine Sulfate
Other Intervention Name(s)
Aralen GENERIC NAME(S): Chloroquine Phosphate
Intervention Description
Antimalarial
Primary Outcome Measure Information:
Title
Hours to recovery
Description
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
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Time fever resolution
Description
Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications
Time Frame
42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Known Porphyria Known myasthenia gravis Currently pregnant or planning on getting pregnant while on study Breast feeding AST/ALT >five times the upper limit of normal ULN* Bilirubin >five times the ULN* Magnesium <1.4 mEq/L* Calcium <8.4mg/dL >10.6mg/dL* Potassium <3.3 >5.5 mEg/L*
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane O'Halloran, MD PhD
Organizational Affiliation
Washington University School of Medicine (ID-CRU)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine Infectious Disease Clinical Research Unit
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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