Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, Vitamin D, Vitamin B12 With or Without Vitamin C, a Multi-centre, International, Randomized Trial: The International ALLIANCE Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Symptoms
研究概览
简要总结
COVID-19 is a global pandemic. So far encouraging results have been shown in different parts of the world with the utilisation of hydroxycloroquine, zinc, and azithromycin, and early studies into some of these, plus some with Vitamin C, have also proven beneficial. Vitamin D levels have also been shown to be an important indicator to the severity of symptoms in COVID-19 patients.
详细描述
Study Design
Type of study A multi-centre, open-label, randomized controlled trial evaluating the efficacy and safety of therapy with azithromycin, hydroxychloroquine, zinc, vitamin D3/B12 and IV vitamin C compared with azithromycin, hydroxychloroquine, zinc, vitamin D3/B12 in participants with COVID-19.
Expected number of participants The sample size for the study is a minimum of 100 participants in each arm. However, this sample size may change as this trial has an adaptive design.
Allocation procedure Randomization: Eligible patients that have provided informed written consent will be randomized by independent researcher. Randomization will be in randomly permuted blocks (undisclosed sizes to maintain concealment of allocation). The allocation will be communicated to site personnel and participants will be made aware of their assignment. It is not practical to use placebo in this trial.
Stratification: randomization will be stratified by site and age (65 years or younger, over 65 years of age).
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
- Double (Investigator, Outcomes Assessor)
盲法说明
Participants not blinded as they will know whether they are receiving the comparator vitamin c (either IVC) or oral in addition to treatments in the control group; outcomes assessor / investigators conducting statistical analysis will be blinded
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
- •Age ≥ 18 years
- •Provision of informed consent in writing, can be electronic
- •Diagnosis of active COVID-19
排除标准
- •Known G6PD deficiency
- •Contra-indication to hydroxychloroquine, azithromycin or Vitamin C: allergy to study interventions, epilepsy, serious hearing or visual problems, history of severe depression, calcium oxalate stones, advanced liver disease, pregnancy or lactating
- •Already receiving chloroquine, azithromycin, >3 grams Vitamin C daily or an experimental antiviral
- •History of fever (e.g. night sweats, chills) and/or acute respiratory infection (e.g. cough, shortness of breath, sore throat) of more than 7 days' duration. Note, if study numbers not quickly reached, the investigators may decide to include those with symptoms of longer than 7 days
- •Calculated creatinine clearance of < 30 mL/minute
- •Baseline ECG showing: QTc ≥470 for males, QTc ≥480 for females
- •Receipt of a drug known to increase QTc: quetiapine, amiodarone, sotalol
研究组 & 干预措施
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Vitamin C (Dietary Supplement)
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Hydroxychloroquine (Drug)
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Azithromycin (Drug)
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Zinc Citrate (Dietary Supplement)
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Vitamin D3 (Dietary Supplement)
Vitamin C
Participants will receive vitamin C in addition to active comparator treatment:
Inpatients: IV Vitamin C (Sodium Ascorbate) 50mg/kg every 6hrs on day 1 followed by 100mg/kg every 6hrs (4x per day; 400mg/kg/day) for 7 days (average 28g/day; maximum dose of 50g/24hrs for those weighing more than 125kg). Can be converted to 1 gram three times per day PO on hospital discharge) Outpatients: Vitamin C Outpatient trial: 200mg/kg x1 IV, then 1 gram PO three times per day for 7 days;
Plus Active Comparator treatment:
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Vitamin B12 (Dietary Supplement)
Control
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Hydroxychloroquine (Drug)
Control
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Azithromycin (Drug)
Control
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Zinc Citrate (Dietary Supplement)
Control
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Vitamin D3 (Dietary Supplement)
Control
Hydroxychloroquine Hydroxychloroquine 400mg (2x200mg) PO for 1 day, followed by 200mg PO per day for 6 days Azithromycin 500 mg PO on day 1 followed by 250 mg PO once daily for 4 days Zinc Citrate 30mg elemental zinc PO daily Vitamin D3 5,000iu PO daily for 14 days Vitamin B12 (Methylcobalamin) 500mcg PO daily for 14 days
干预措施: Vitamin B12 (Dietary Supplement)
结局指标
主要结局
Symptoms
时间窗: once daily for 15 days since enrollment/baseline at admission to hospital
Composite measure: Change in severity and duration of symptoms
invasive mechanical ventilation or mortality
时间窗: any time within 15 days from enrolment
need for invasive mechanical ventilation or mortality within 15 days from enrolment
Length of hospital stay
时间窗: at 15 and 45 days since admission/ enrolment
total number of days in hospital since admission
次要结局
- mechanical ventilation(at 15 and 45 days since enrolment)
- oxygen(15 and 45 days since enrolment)
- Mortality(15 and 45 days since enrolment)
- Extracorporeal support(15 and 45 days since enrolment)
- ICU(15 and 45 days since enrolment)
- days in ICU(15 and 45 days since enrolment)
- renal replacement therapy(15 and 45 days since enrolment)
- days in hospital(15 and 45 days since enrolment)