COVID-19Phase 3NCT04641195

Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India

A Phase 3 study testing Vitamin D3 (cholecalciferol), Zinc (zinc gluconate) and Zinc (zinc gluconate) & Vitamin D (cholecalciferol) in people with COVID-19, run by Harvard School of Public Health (HSPH) at 2 sites in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to assess the effect of vitamin D and/or zinc supplementation on improving COVID-19 treatment outcomes. The effects of vitamin D, zinc, and both vitamin D and zinc together will be investigated among COVID-19 patients in India. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: COVID-19
What is being tested?: Vitamin D3 (cholecalciferol), Zinc (zinc gluconate) and Zinc (zinc gluconate) & Vitamin D (cholecalciferol)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 181 participants
Where: 2 sitesIndia
Study dates: 22 Apr 2021to 1 Aug 2022
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Aged >=18 years old
Polymerase chain reaction (PCR) or Rapid Antigen Test (RAT)-confirmed infection with SARS-COV2
Provide informed consent

Who cannot join

Pregnancy
Enrollment in other clinical trials

Trial locations and contacts

2 sites in 1 country.

India2 sites

Saifee Hospital
Mumbai, Maharashtra
King Edward Memorial (KEM) Hospital
Pune, Maharashtra

Other trials in India

About this study

Official title: A Randomized Trial to Determine the Effect of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India

Read the detailed description

This study is a 2x2 factorial randomized double-blind, placebo-controlled trial to examine the effectiveness of vitamin D and zinc supplements as immune-based therapy among COVID-19 patients in India. The study is also examining the immunological response to COVID-19 and the effect of the intervention on specific biomarkers of immune and endothelial activation that are independent and quantitative predictors of severity and mortality in other severe infections. The primary aims are to determine the effect of vitamin D supplementation versus placebo on time to recovery among patients hospitalized with COVID-19; and to determine the effect of zinc supplementation versus placebo on time to recovery among patients hospitalized with COVID-19. As secondary aims, this study is also investigating the effect of vitamin D or zinc supplementation on all-cause mortality. necessity for assisted ventilation, individual symptoms duration, duration of hospital stay and biomarkers including vitamin D, Zinc, Interleukin 6 (IL-6), Angiopoietin-2, sTREM-1, immunoglobulin G (IgG) and immunoglobulin M (IgM).

Eligible individuals are randomly assigned to one of four groups: (1) Vitamin D (180,000 IU bolus at enrollment, followed by 2000 IU daily); (2) Zinc (placebo at enrollment followed by one daily dose of 40 mg); (3) Vitamin D and Zinc; or (4) Placebo. Daily supplements start at the hospital and continue after discharge for a total of 8 weeks. Active data collection occurs daily while patients are hospitalized and at least twice per week via telephone after discharge. A clinical exam occurs at 8 weeks and longer-term symptoms are assessed at 3 months.

Conditions: COVID-19
Being tested: Vitamin D3 (cholecalciferol), Zinc (zinc gluconate), Zinc (zinc gluconate) & Vitamin D (cholecalciferol), Placebo
Keywords: COVID-19, Vitamin-D3, Zinc, Nutrition support, Host-directed therapy, Clinical management, India
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vitamin D3 (cholecalciferol)Dietary supplement
180,000 international units (IU) of vitamin D3 at enrollment, followed by 2000 IU once per day from enrollment to 8 weeks
Zinc (zinc gluconate)Dietary supplement
40mg of zinc gluconate taken once per day from enrollment to 8 weeks
Zinc (zinc gluconate) & Vitamin D (cholecalciferol)Dietary supplement
180,000 IU of vitamin D3 at enrollment, followed by 2000 IU of vitamin D3 and 40mg of zinc gluconate once per day from enrollment to 8 weeks
PlaceboOther
Placebo vitamin D bolus at enrollment followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements.

Study groups in NCT04641195
Study group	Role	What they receive
Placebo- Placebo	Placebo comparator	Participants in the PLACEBO-PLACEBO group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements. Receives: Other: Placebo
Vitamin D- Placebo	Experimental	Participants in the VITAMIN D-PLACEBO group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and daily placebo zinc supplements. Receives: Dietary Supplement: Vitamin D3 (cholecalciferol)
Placebo-Zinc	Experimental	Participants in the PLACEBO-ZINC group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and actual daily zinc supplements. Receives: Dietary Supplement: Zinc (zinc gluconate)
Vitamin D- Zinc	Experimental	Participants in the VITAMIN D-ZINC group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and actual daily zinc supplements. Receives: Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)

What is being measured

The primary outcome is the main question the study is designed to answer.

Time to recovery
Defined as resolution of fever, cough and shortness of breath relative to baseline
Measured: Up to 8 weeks

Secondary outcomes (11)

All-cause mortality
Measured: Up to 8 weeks
Necessity for assisted ventilation
Measured: Up to 8 weeks
Individual symptoms duration
Measured: Up to 8 weeks
Vitamin D
Measured: At 8 weeks
Zinc
Measured: At 8 weeks
Interleukin 6 (IL-6)
Measured: At 8 weeks
Angiopoietin-2
Measured: At 8 weeks
sTREM-1
Measured: At 8 weeks
Immunoglobulin M (IgM)
Measured: At 8 weeks
Immunoglobulin (IgG)
Measured: At 8 weeks
Duration of hospital stay
Measured: Up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Apr 20211 Aug 2022

First posted23 Nov 2020
Study start22 Apr 2021
Primary completion1 Jul 2022
Study completion1 Aug 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for COVID-19Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Model description: The effect of both interventions (vitamin D or zinc) will be investigated simultaneously using a factorial design.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 181 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04641195
Sponsor's protocol ID: VR3- 172649
Status last verified: Sep 2022
First submitted: 19 Nov 2020
Last updated: 19 Sep 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Phiri TN, Dumbura C, Mutasa K, Ngosa D, Chuulu N, Majo FD, Rukobo S, Bourke CD, Amadi B, Bwakura-Dangarembizi M, Martineau AR, Prendergast AJ, Kelly P. A cross-sectional analysis of vitamin D status and associated factors in children recovering from severe acute malnutrition in Zambia and Zimbabwe. PLoS One. 2026 Aug 28;21(8):e0355404. doi: 10.1371/journal.pone.0355404. eCollection 2026.
PubMed 42664277
Partap U, Sharma KK, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Mistry N, Kain KC, Dholakia Y, Fawzi WW. Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial. Curr Dev Nutr. 2023 Jul 11;7(8):101971. doi: 10.1016/j.cdnut.2023.101971. eCollection 2023 Aug.
PubMed 37560461
Martineau AR. Vitamin D in the prevention or treatment of COVID-19. Proc Nutr Soc. 2023 May;82(2):200-207. doi: 10.1017/S0029665122002798. Epub 2022 Nov 11.
PubMed 36366796
Sharma KK, Partap U, Mistry N, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Kain KC, Dholakia Y, Fawzi WW. Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol. BMJ Open. 2022 Aug 29;12(8):e061301. doi: 10.1136/bmjopen-2022-061301.
PubMed 36038172

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Trial to Determine the Effect of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India
ClinicalTrials.gov ID: NCT04641195
Acronym / sponsor ID: VR3- 172649
Conditions: COVID-19
Keywords: COVID-19, Vitamin-D3, Zinc, Nutrition support, Host-directed therapy, Clinical management, India
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 181 participants (actual)
Lead sponsor: Harvard School of Public Health (HSPH)University, hospital or other
Collaborators: Foundation for Medical Research, University Health Network, Toronto
Study start: 22 Apr 2021 (actual)
Primary completion: 1 Jul 2022 (actual)
Study completion: 1 Aug 2022 (actual)
First posted: 23 Nov 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: The effect of both interventions (vitamin D or zinc) will be investigated simultaneously using a factorial design.

Arm	Type	Receives
Placebo- Placebo	Placebo comparator	Other: PlaceboParticipants in the PLACEBO-PLACEBO group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements.
Vitamin D- Placebo	Experimental	Dietary Supplement: Vitamin D3 (cholecalciferol)Participants in the VITAMIN D-PLACEBO group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and daily placebo zinc supplements.
Placebo-Zinc	Experimental	Dietary Supplement: Zinc (zinc gluconate)Participants in the PLACEBO-ZINC group will receive a placebo vitamin D bolus at the hospital followed by placebo daily vitamin D maintenance doses and actual daily zinc supplements.
Vitamin D- Zinc	Experimental	Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)Participants in the VITAMIN D-ZINC group will receive an actual vitamin D bolus at the hospital followed by actual daily vitamin D maintenance doses and actual daily zinc supplements.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Aged >=18 years old
Polymerase chain reaction (PCR) or Rapid Antigen Test (RAT)-confirmed infection with SARS-COV2
Provide informed consent

Key exclusion criteria (2 listed)

Pregnancy
Enrollment in other clinical trials

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Vitamin D3 (cholecalciferol)180,000 international units (IU) of vitamin D3 at enrollment, followed by 2000 IU once per day from enrollment to 8 weeks	Dietary supplement	Vitamin D- Placebo
Zinc (zinc gluconate)40mg of zinc gluconate taken once per day from enrollment to 8 weeks	Dietary supplement	Placebo-Zinc
Zinc (zinc gluconate) & Vitamin D (cholecalciferol)180,000 IU of vitamin D3 at enrollment, followed by 2000 IU of vitamin D3 and 40mg of zinc gluconate once per day from enrollment to 8 weeks	Dietary supplement	Vitamin D- Zinc
PlaceboPlacebo vitamin D bolus at enrollment followed by placebo daily vitamin D maintenance doses and placebo daily zinc supplements.	Other	Placebo- Placebo

Primary outcome

Time to recovery
Time frame: Up to 8 weeks
Defined as resolution of fever, cough and shortness of breath relative to baseline

11 secondary outcomes

All-cause mortality
Time frame: Up to 8 weeks
Necessity for assisted ventilation
Time frame: Up to 8 weeks
Individual symptoms duration
Time frame: Up to 8 weeks
Vitamin D
Time frame: At 8 weeks
Zinc
Time frame: At 8 weeks
Interleukin 6 (IL-6)
Time frame: At 8 weeks
Angiopoietin-2
Time frame: At 8 weeks
sTREM-1
Time frame: At 8 weeks
Immunoglobulin M (IgM)
Time frame: At 8 weeks
Immunoglobulin (IgG)
Time frame: At 8 weeks
Duration of hospital stay
Time frame: Up to 8 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2022.
Derived from this study: PubMed 42664277Phiri TN, Dumbura C, Mutasa K, Ngosa D, Chuulu N, Majo FD, Rukobo S, Bourke CD, Amadi B, Bwakura-Dangarembizi M, Martineau AR, Prendergast AJ, Kelly P. A cross-sectional analysis of vitamin D status and associated factors in children recovering from severe acute malnutrition in Zambia and Zimbabwe. PLoS One. 2026 Aug 28;21(8):e0355404. doi: 10.1371/journal.pone.0355404. eCollection 2026.
Derived from this study: PubMed 37560461Partap U, Sharma KK, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Mistry N, Kain KC, Dholakia Y, Fawzi WW. Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial. Curr Dev Nutr. 2023 Jul 11;7(8):101971. doi: 10.1016/j.cdnut.2023.101971. eCollection 2023 Aug.
Derived from this study: PubMed 36366796Martineau AR. Vitamin D in the prevention or treatment of COVID-19. Proc Nutr Soc. 2023 May;82(2):200-207. doi: 10.1017/S0029665122002798. Epub 2022 Nov 11.
Derived from this study: PubMed 36038172Sharma KK, Partap U, Mistry N, Marathe Y, Wang M, Shaikh S, D'Costa P, Gupta G, Bromage S, Hemler EC, Kain KC, Dholakia Y, Fawzi WW. Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol. BMJ Open. 2022 Aug 29;12(8):e061301. doi: 10.1136/bmjopen-2022-061301.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Wafaie W Wafaie, MBBS, MPH, MS, DrPH principal investigator

Harvard School of Public Health (HSPH)

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to recovery (time frame: Up to 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04641195, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2022.