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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04395768




Registration number
NCT04395768
Ethics application status
Date submitted
18/05/2020
Date registered
20/05/2020
Date last updated
11/09/2020

Titles & IDs
Public title
International ALLIANCE Study of Therapies to Prevent Progression of COVID-19
Scientific title
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
Secondary ID [1] 0 0
Alliance-COVID19
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID19 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Vitamin C
Treatment: Drugs - Hydroxychloroquine
Treatment: Drugs - Azithromycin
Other interventions - Zinc Citrate
Other interventions - Vitamin D3
Other interventions - Vitamin B12

Experimental: 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

Active Comparator: 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


Other interventions: Vitamin C
In addition to the active comparator, which is a combination of 2 drugs and 3 dietary supplements, the experimental treatment arm will also receive Vitamin C (intravenous or oral)

Treatment: Drugs: Hydroxychloroquine
Active comparator group will receive: a combination of 2 drugs and 3 dietary supplements

Treatment: Drugs: Azithromycin
Active comparator group will receive: a combination of 2 drugs and 3 dietary supplements

Other interventions: Zinc Citrate
Active comparator group will receive: a combination of 2 drugs and 3 dietary supplements

Other interventions: Vitamin D3
Active comparator group will receive: a combination of 2 drugs and 3 dietary supplements

Other interventions: Vitamin B12
Active comparator group will receive: a combination of 2 drugs and 3 dietary supplements

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Symptoms - Composite measure: Change in severity and duration of symptoms
Timepoint [1] 0 0
once daily for 15 days since enrollment/baseline at admission to hospital
Primary outcome [2] 0 0
Length of hospital stay - total number of days in hospital since admission
Timepoint [2] 0 0
at 15 and 45 days since admission/ enrolment
Primary outcome [3] 0 0
invasive mechanical ventilation or mortality - need for invasive mechanical ventilation or mortality within 15 days from enrolment
Timepoint [3] 0 0
any time within 15 days from enrolment
Secondary outcome [1] 0 0
Mortality - Death
Timepoint [1] 0 0
15 and 45 days since enrolment
Secondary outcome [2] 0 0
mechanical ventilation - need for and number of days of invasive mechanical ventilation, in case of no need for mechanical ventilation: days=0
Timepoint [2] 0 0
at 15 and 45 days since enrolment
Secondary outcome [3] 0 0
oxygen - need for and number of days for humidified high-flow oxygen
Timepoint [3] 0 0
15 and 45 days since enrolment
Secondary outcome [4] 0 0
ICU - admission to ICU (intensive care unit)
Timepoint [4] 0 0
15 and 45 days since enrolment
Secondary outcome [5] 0 0
days in hospital - days in hospital
Timepoint [5] 0 0
15 and 45 days since enrolment
Secondary outcome [6] 0 0
days in ICU - days in ICU
Timepoint [6] 0 0
15 and 45 days since enrolment
Secondary outcome [7] 0 0
renal replacement therapy - need for and days of renal replacement therapy
Timepoint [7] 0 0
15 and 45 days since enrolment
Secondary outcome [8] 0 0
Extracorporeal support - need for and days of Extracorporeal support
Timepoint [8] 0 0
15 and 45 days since enrolment

Eligibility
Key inclusion criteria
1. Age = 18 years

2. Provision of informed consent in writing, can be electronic

3. Diagnosis of active COVID-19
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known G6PD deficiency

2. 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

3. Already receiving chloroquine, azithromycin, >3 grams Vitamin C daily or an
experimental antiviral

4. 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

5. Calculated creatinine clearance of < 30 mL/minute

6. Baseline ECG showing: QTc =470 for males, QTc =480 for females

7. Receipt of a drug known to increase QTc: quetiapine, amiodarone, sotalol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
National Institute of Integrative Medicine - Melbourne
Recruitment postcode(s) [1] 0 0
3122 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
National Institute of Integrative Medicine, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04395768
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Karin Ried, PhD
Address 0 0
National Institute of Integrative Medicine, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Karin Ried, PhD
Address 0 0
Country 0 0
Phone 0 0
0061399129545
Fax 0 0
Email 0 0
karinried@niim.com.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04395768