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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Terminated
CT.gov ID
NCT04341727
Collaborator
(none)
31
2
4
11.9
15.5
1.3

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 4, 2020
Actual Primary Completion Date :
Apr 1, 2021
Actual Study Completion Date :
Apr 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Hydroxychloroquine alone

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
anti-rheumatic drug (DMARD)
Other Names:
  • HYDROXYCHLOROQUINE Plaquenil
  • Active Comparator: Hydroxychloroquine plus azithromycin

    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
    anti-rheumatic drug (DMARD)
    Other Names:
  • HYDROXYCHLOROQUINE Plaquenil
  • Drug: Azithromycin
    Antibiotic
    Other Names:
  • COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin
  • Active Comparator: Chloroquine alone

    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
    Antimalarial
    Other Names:
  • Aralen GENERIC NAME(S): Chloroquine Phosphate
  • Active Comparator: Chloroquine plus azithromycin

    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
    Antibiotic
    Other Names:
  • COMMON BRAND(S): Zithromax GENERIC NAME(S): Azithromycin
  • Drug: Chloroquine Sulfate
    Antimalarial
    Other Names:
  • Aralen GENERIC NAME(S): Chloroquine Phosphate
  • Outcome Measures

    Primary Outcome Measures

    1. Hours to recovery [42 days]

      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

    1. Time fever resolution [42 days]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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*

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Infectious Disease Clinical Research Unit Saint Louis Missouri United States 63110
    2 Washington University School of Medicine Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Jane O'Halloran, MD PhD, Washington University School of Medicine (ID-CRU)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jane O'Halloran, Assistant Professor in Medicine, Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT04341727
    Other Study ID Numbers:
    • 202003188
    First Posted:
    Apr 10, 2020
    Last Update Posted:
    Oct 7, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 7, 2021