Coronavirus Infection
Conditions
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.
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 with the 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 standard of care SOC will be collected from medical records.
Interventions
DRUGHydroxychloroquine Sulfate
anti-rheumatic drug (DMARD)
DRUGAzithromycin
Antibiotic
Antimalarial
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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\*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 in each Arm/Group,respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 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 in each Arm/Group,respectively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Hydroxychloroquine Sulfate: anti-rheumatic drug (DMARD) | 9 |
| 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.
Hydroxychloroquine Sulfate: anti-rheumatic drug (DMARD)
Azithromycin: Antibiotic | 7 |
| 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.
Chloroquine Sulfate: Antimalarial | 7 |
| 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.
Azithromycin: Antibiotic
Chloroquine Sulfate: Antimalarial | 7 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Hydroxychloroquine Alone | Hydroxychloroquine Plus Azithromycin | Chloroquine Alone | Chloroquine Plus Azithromycin | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55 years | 55 years | 54 years | 56 years | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 4 Participants | 7 Participants | 6 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 4 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 7 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 4 / 9 | 2 / 7 | 3 / 7 | 3 / 7 |
| serious Total, serious adverse events | 1 / 9 | 2 / 7 | 1 / 7 | 1 / 7 |
Outcome results
Primary
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.
Time frame: 42 days
Population: The sample size of 30 was well below the threshold for analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine Alone | Hours to Recovery | 96 hours |
| Hydroxychloroquine Plus Azithromycin | Hours to Recovery | 120 hours |
| Chloroquine Alone | Hours to Recovery | 168 hours |
| Chloroquine Plus Azithromycin | Hours to Recovery | 240 hours |
Secondary
Time to 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 in each Arm/Group,respectively.
Time frame: 42 days
Population: The sample was well below the threshold for analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine Alone | Time to Fever Resolution | 72 hours |
| Hydroxychloroquine Plus Azithromycin | Time to Fever Resolution | 96 hours |
| Chloroquine Alone | Time to Fever Resolution | 72 hours |
| Chloroquine Plus Azithromycin | Time to Fever Resolution | 96 hours |