Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

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).

Duration of the study period for each subject Participants will be followed for 45 days from the time of randomization. Data of events occurring during hospital will be obtained from hospital records supplemented by a telephone call or follow up at 7-10 days and at 45 days after randomization.

Adaptive design features

Adaptive intervention arms: The Steering Committee will keep abreast of other ongoing trials and if other promising interventions emerge, may recommend adding (or replacing) one arm with the new promising intervention.

Adaptive sample size: Sample size calculations are based on disease progression rates that are not well known. The investigators remain flexible, and the Data Safety Committee (DSMC) will be monitoring the possibility that the assumptions for sample size calculations may be modified with emerging information from this trial or other ongoing trials. If recruitment is going well, the steering committee may decide to extend recruitment as long as the independent DSMC does not terminate the trial for clear evidence of efficacy, futility (low probability) to detect a clinically meaningful difference (e.g. a 20% RRR in events) or concerns about safety.

Study Procedures Direct electronic data entry will be utilized in this trial. The investigators will use Redcap platform and software (www.project-redcap.org).

Consenting process Due to the stringent measures in infection control in hospitals, digitalised consent will be obtained instead of written consent on paper. Be this preferably from the patient or his legal representative. All patients will be in strict contact and droplet precautions and there may be an imperative to minimise use of personal protective equipment (PPE) by staff due to resource limitations.

The consenting process will be as follows:

- The clinical team will inform a potential participant in the trial that an investigator will contact them

- To minimise PPE use, the investigator will make telephone contact with the patient. If an interpreter is required for the consent discussion, this will be by the telephone interpreter service. An informed consent discussion will be held with each participant by a site investigator or their delegate.

- The Patient Information Sheet and Consent form (PICF) will be emailed to the patient or the clinical team will take it into the room for viewing by the patient. These documents will be left in the patient's room

- The participant will be given time to ask questions and consider whether to participate in the research.

- Verbal consent will be recorded in both the participant's medical record and study consent form. This will state that the terms and conditions were all read and agreed to and all questions asked were answered. The full PICF, including the signed consent page (by the investigator), will be uploaded into the electronic database.

- If the patient is too unwell or is unable to use a digital device, to personally give consent, written consent can be obtained from their next of kin, or other adult family members, or partner or legal representative.

- The following day, the investigator or clinical team will verbally confirm with the participant that they have consented to participate. A copy of the signed consent form will then either be emailed to the participant or sent via post. The participant, their next of kin or legal representative will send a return email confirming their consent.

Interventions

Blinding: Participants and healthcare providers will not be blinded to treatment. To account for this, the investigators have objective outcome definitions to minimize the opportunity for bias to influence event assessment.

Consenting participants will be randomized to receive therapy with azithromycin, hydroxychloroquine, zinc, Vitamin D3/B12 and IV vitamin C or azithromycin, zinc and hydroxychloroquine, Vitamin D3/B12.

For further details see: Arms & Interventions

The investigators will place no constraints for treating physicians on the therapies with respect to usual care. The investigators will document information on all key co-interventions, including information on drugs at the time of randomization and post randomization /during hospitalization.

Data collection The investigators will collect participant sex, age, disease severity, comorbidities (smoking, diabetes, heart disease, lung disease, immunosuppression, etc.), other medications, and trial outcomes.

Participants in this trial will be swabbed (nasal and/or oral) on approximately days 0, 3 and 7 for quantitative polymerase chain reaction (PCR) assessment of viral titre.

Study Outcomes For details see primary & secondary outcome section.

In addition, the investigators will collect data on:

WHO Master Protocol ordinal score at day 15:

1. Not hospitalized, no limitations on activities

2. Not hospitalized, limitation on activities;

3. Hospitalized, not requiring supplemental oxygen;

4. Hospitalized, requiring supplemental oxygen;

5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;

6. Hospitalized, on invasive mechanical ventilation or ECMO;

7. Death.

Secondary safety outcomes

- QTc prolongation (>500ms) 24 hours following initial dose of study drugs

- Serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death in hospital

- Any of the following adverse events in first 10 days from enrolment.

- Diarrhoea - grade 2 or greater

- Nausea - grade 2 or greater

- Vomiting - grade 2 or greater

Statistical Considerations

Sample size calculation The minimum sample size required is N=100 in each intervention arm in order to have 80% statistical power to detect a 30% relative risk reduction (RRR) in the proportion progressing to mechanical ventilation or death, assuming a standard-of-care risk of progression of 30%. Since participants will be hospitalized, a minimal (<1%) loss to follow-up is assumed.

Statistical analysis methods The primary analysis of efficacy will be conducted under the intention-to-treat principle; all randomized participants will be included in the analyses. All results will be analyzed with 2-sided level of significance of 0.05. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04395768
Study type Interventional
Source National Institute of Integrative Medicine, Australia
Contact Karin Ried, PhD
Phone 0061399129545
Email [email protected]
Status Recruiting
Phase Phase 2
Start date September 9, 2020
Completion date December 31, 2021

See also
  Status Clinical Trial Phase
Recruiting NCT04555096 - A Trial of GC4419 in Patients With Critical Illness Due to COVID-19 Phase 2
Enrolling by invitation NCT04508777 - COVID SAFE: COVID-19 Screening Assessment for Exposure
Completed NCT04506268 - COVID-19 SAFE Enrollment N/A
Recruiting NCT04546737 - Study of Morphological, Spectral and Metabolic Manifestations of Neurological Complications in Covid-19 Patients N/A
Recruiting NCT04581915 - PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19 Phase 2/Phase 3
Active, not recruiting NCT04542993 - Can SARS-CoV-2 Viral Load and COVID-19 Disease Severity be Reduced by Resveratrol-assisted Zinc Therapy Phase 2
Completed NCT04494646 - BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19) Phase 2
Not yet recruiting NCT04543006 - Persistence of Neutralizing Antibodies 6 and 12 Months After a Covid-19 N/A
Completed NCT04532294 - Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/COVID-19) Neutralizing Antibody in Healthy Participants Phase 1
Recruiting NCT04387292 - Ocular Sequelae of Patients Hospitalized for Respiratory Failure During the COVID-19 Epidemic N/A
Not yet recruiting NCT04527211 - Effectiveness and Safety of Ivermectin for the Prevention of Covid-19 Infection in Colombian Health Personnel Phase 3
Completed NCT04610502 - Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 Serum in COVID-19 Patients Phase 2
Recruiting NCT04505774 - Anti-thrombotics for Adults Hospitalized With COVID-19 (ACTIV-4) Phase 4
Active, not recruiting NCT04596839 - Antiviral Activity and Safety of Remdesivir in Bangladeshi Patients With Severe Coronavirus Disease (COVID-19) Phase 2
Not yet recruiting NCT04361032 - Assessment of Efficacy and Safety of Tocilizumab Compared to DefeROxamine, Associated With Standards Treatments in COVID-19 (+) Patients Hospitalized In Intensive Care in Tunisia Phase 3
Completed NCT04534569 - Expert Panel Statement for the Respiratory Management of COVID-19 Related Acute Respiratory Failure (C-ARF)
Recruiting NCT04872309 - MUlti-nuclear MR Imaging Investigation of Respiratory Disease-associated CHanges in Lung Physiology
Withdrawn NCT04338126 - Tranexamic Acid (TXA) and Corona Virus 2019 (COVID19) in Inpatients Phase 2
Recruiting NCT04870307 - Community-engaged Approaches to Testing in Community and Healthcare Settings for Underserved Populations N/A
Recruiting NCT04410510 - P2Et Extract in the Symptomatic Treatment of Subjects With COVID-19 Phase 2/Phase 3