Open-label, Randomized Controlled Trial of Hydroxychloroquine, Hydroxychloroquine Plus Azithromycin, Chloroquine Alone, Chloroquine Plus Azithromycin in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Hours to Recovery
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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*
研究组 & 干预措施
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.
干预措施: Hydroxychloroquine Sulfate (Drug)
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.
干预措施: Hydroxychloroquine Sulfate (Drug)
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.
干预措施: Azithromycin (Drug)
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.
干预措施: Chloroquine Sulfate (Drug)
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.
干预措施: Azithromycin (Drug)
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.
干预措施: Chloroquine Sulfate (Drug)
结局指标
主要结局
Hours to Recovery
时间窗: 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.
次要结局
- Time to Fever Resolution(42 days)
研究者
Jane O'Halloran
Assistant Professor in Medicine
Washington University School of Medicine