RCT,Double Blind, Placebo to Evaluate the Effect of Zinc and Ascorbic Acid Supplementation in COVID-19 Positive Hospitalized Patients in BSMMU

In view of the emerging COVID-19 pandemic caused by SARS-coV-2 virus, the search for
potential protective and therapeutic antiviral strategies is of particular and urgent
interest. Despite the lack of clinical data, certain indications suggest that modulation of
zinc status may be beneficial in COVID-19. The use of vitamin C could be effective in terms
of mortality and outcomes in patients with covid-19 pneumonia. Zinc and vitamin C are the
over the counter supplementation and other study shows the effect of this in respiratory
tract infection. This type of study is not done in Bangladesh. So, this will give a baseline
data for further study which will help the researcher.

C. Related with socio-economic development: Health economic analysis will be done by total
duration of hospital stay in comparing with total cost during admission in hospital. Benefits
of this analysis will consider the:

- Reduced the severity and symptoms which will decrease the risk of mortality among the
patients.

- Duration of hospital stay will reduce the treatment cost and as well the price of this
nutrients supplements is very low.

- Costs are measured by the recorded number of patients and duration of hospital stay in
both study groups. Number and duration will be recorded.

3. Work plan:

Methodology Types of study: Randomized double-blind placebo Controlled Trial Place of study:
Department of pharmacology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka.

Study population:

Eligible participants for randomization are COVID-19 positive patients admitted in BSMMU

- Ages Eligible for Study: 18 Years and older (Adult, Older Adult)

- Sexes Eligible for Study: All

- Accepts Healthy Volunteers: No Criteria

Inclusion Criteria:

- ≥ 18 years presenting symptoms who test positive for COVID-19

- Moderate to severe patients obtained consent

- Hypoxic respiratory failure (saturation <90% on air at rest or increasing oxygen
requirement)

- Chest examination findings of bilateral crackles on auscultation or chest x-ray showing
bilateral infiltrates

- C-Reactive Protein > 50mg/L

- women of childbearing potential who meet the above and have a negative pregnancy test.

Exclusion Criteria:

- Pregnant women: Current known pregnancy positive pregnancy test.

- Lactating women.

- Documented history of mental illnesses

- Multi-organ failure

- Severe ARDS (requiring ventilator support on presentation in the form of invasive or
non-invasive ventilation)

- Septic Shock

- Drug allergy/intolerance Sampling technique: Patients who meet the inclusion criteria
and who provide consent will be randomized by online graph pad software by using
computer.

Sample size:

Sample size calculation P1 (1-P1) + P2 (1-P2) × (Zα+ Zβ)2 N = (P1- P2)2 Where, N= sample size
P1 = control group response 50 % P2= treatment group response 20% Zα = Z value at a definite
level of significance1.96 at 5% level of significance Zβ = Z value at a definite power 1.28
at 90 % power (when β is 0.10)

0.5 (1-0.5) + 0.2 (1- 0.2) × (1.96+ 1.28)2 N= (0.5-0.2)2

= 48 According to this formula sample size will be 48 in each group. We estimate that the
drop-out rate will be 5%, total 50 patients will be in each group

Study variables

1. Demographic variables:

- Age

- Sex

- Ethnicity

- Past medical history - Hypertension, use of ACEI or ARB, DM, IHD, COPD, CKD, Obesity
(BMI) and Cancer

- Presenting symptoms (dry cough, productive cough, fever, sore throat, myalgia, lethargy,
headache, breathlessness, nausea, diarrhea and any other)

- Baseline observations on day of initiating treatment (Day 0): oxygen saturation (SpO2),
fraction of inspired oxygen (FiO2), SpO2/FiO2 ratio, respiratory rate, body temperature,
neutrophil-lymphocyte ratio, C-Reactive Protein & findings of bilateral infiltrates on
chest-x-ray.

- Follow-up observations after randomization on Day 1,2,3,4 and 5 for SpO2/FiO2 ratio,
respiratory rate, body temperature and C-Reactive Protein

- Length of stay (in days)

- Use of ventilator support (invasive or non-invasive ventilation)

- Side effects of drugs

- In-patient mortality

Methods:

Each patient will give informed consent and demographic data (age, sex) will be obtained and
documented. All patients will receive standard routine medical care throughout the study.
After collecting baseline data patients will be assigned to respective group randomly. A
compliance sheet will be maintained for each patient. Regularity of drug intake will be
ensured and recorded in the patient's compliance sheets by research assistant. Patients will
be asked to report for any adverse effects of the medication given during the period of
study. The study will follow the principle of the declaration of Helsinki and of the world
medical assembly. The study will be conducted after the approval of the protocol by the
institutional review board (IRB). Each patient will be assured that the present therapy would
not provide harm, however in case of any untoward effect, assurance would be provided for
proper medical treatment and care from the part of the researcher. Each patient had complete
right to withdraw from the study at any time during the research.

Recruitment procedure for patients according to symptoms and who consent to participate in
the study will be randomly allocated immediately after hospital admission to one of two
groups; intervention (I), or placebo group (P).

Pre-designed case record form (CRF) will be used for collecting data, which will also contain
the result of the study. The information collected in the CRF will be reviewed and
inconsistencies will be investigated and clarified. Data from case record forms will be
anonymized and stored securely in a secure online web-based portal. The study outline is
presented in Figure 1.

Study procedure:

Randomization - After determining the sample size, patients will randomly be allocated into
two groups to the patient's enrollment for the study. Randomization will be done by online
graph pad software by using computer. the software automatically generated two distinct sets
of numbers after giving necessary inputs (sample size, sets of number). The online graph pad
calculator equally distributed the patients into two comparable groups. The randomization
will conduct by a competent third group person, a professor of this University who has no
relationship with this study.

Blinding - Immediately after randomization, random numbers of the two sets will assigned as
patients code number. One set will be designated as intervention group and another group will
placebo group. Two sets of code number that belongs to the intervention group and placebo
group will be written with patient's id number. this total procedure will be conducted by the
person unrelated to this research. Thus, the participants, caregiver, outcome assessor and
the analyst, who require being blind for such study will effectively blind.

Allocation cancelation: In order to prevent selection bias, concealment of allocation will be
done. Third person allocated two distinct sets of random numbers into intervention group and
placebo group. The allocation code written in two different paper document and preserved in
two separate pen drive which will sealed within two different envelop. The sealed enveloped
will be preserved to another two distinguished professors. So, intervention allocation will
not be known to any person involve in the research.