Older Adults (65 Years and Older)ZOOM OUTNCT07367412
Zinc Supplementation and Infections in Older Medical Patients
A study testing Zinc (zinc sulphate) in people with Older Adults (65 Years and Older) and Medical Patients in the Emergency Department, run by Herlev Hospital at 2 sites in Denmark.
Trial summary
The goal of this clinical trial is to learn about the effect of zinc supplementation once daily for 12 months in older acute medical patients. The main question it aims to answer is: Can daily zinc supplementation for 12 months increase Days Alive and Out of Hospital (DAOH)? Researchers will compare zinc… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Older Adults (65 Years and Older), Medical Patients in the Emergency Department
- What is being tested?
- Zinc (zinc sulphate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8,000 participants
- Where
- 2 sitesDenmark
- Study dates
- 1 Feb 2026to 15 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- All medical patients aged ≥ 65 years assessed at the Medical Emergency Department, Herlev Hospital
Who cannot join
- Self-supplementing with zinc at time of assessment (> 10 mg zinc/day)
- Terminal illness (life expectancy < 6 months, estimated by Clinical Frailty Scale ≥8)
- Patients receiving parenteral nutrition (partial or complete)
- Patients treated with hemodialysis or peritoneal dialysis
- Patients know with known severe dementia
- Patients who do not understand Danish and patients with temporary civil person registration numbers (CPR)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites, 2 recruiting
- Recruiting
Department of Medicine
Herlev, Copenhagen, 2730
Cecilia M Lund, MD, PhD, +4538686112, cecilia.margareta.lund.01@regionh.dk
- Not yet recruiting
Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte
Herlev, 2730
Cecilia M Lund, Senior consultant, PhD, +45 38686112, cecilia.margareta.lund@regionh.dk
Pernille H Ellegaard, MD, PhD student, pernille.holm.ellegaard.01@regionh.dk
About this study
Official title: Effect of Zinc Supplementation on Occurrence of Infections in Older Medical Patients (ZOOM) - a Cluster Randomized Controlled Trial (ZOOM OUT).
The goal of this clinical trial is to learn about the effect of zinc supplementation once daily for 12 months in older acute medical patients. The main question it aims to answer is:
- Can daily zinc supplementation for 12 months increase Days Alive and Out of Hospital (DAOH)? Researchers will compare zinc supplementation to a control group, a group who do not receive zinc supplementation, to see if zinc supplementation can increase Days Alive and Out of Hospital, reduce antibiotic use, readmissions and mortality.
Read more
Participants will take 22 mg zinc supplementation once daily for 12 months or not.
The researchers will draw data on readmissions, antibiotic use and mortality during the 12 months follow-up period.
Read the detailed description
- Study purpose Older adults are at increased risk of micronutrient deficiencies, including zinc, due to sparse food intake. Zinc deficiency is known to increase the susceptibility to infections, further exacerbating the vulnerability of older adults to health complications. Infections are common among older adults and are a leading causes of acute hospital admissions and readmissions. The hypothesis is that zinc supplementation for older acutely admitted medical patients can increase Days Alive and Out of Hospital regardless of baseline plasma zinc level Objectives: Primary objective: To test in older acute medical patients if zinc supplementation once daily for 12 months can increase Days Alive and Out of Hospital. Secondary objectives: To evaluate if zinc supplementation once daily can reduce antibiotic use, readmissions and mortality during the 12 months follow-up period.
- Short background A large proportion of older adults are malnourished, which can lead to increased morbidity, mortality, prolonged hospitalization and reduced quality of life (QoL). With malnutrition the patient lacks vitamins and minerals, including zinc, which is essential for older adults. Early detection and treatment of malnutrition has been shown to be beneficial for patients, including reducing length of stay in the hospital. The older adults are at increased risk of zinc deficiency, with less than half of the free-living older adults having a sufficient zinc intake. Zinc is essential for immune function and acute deficiency weakens both innate and adaptive immunity, increasing susceptibility to infections. The effects of zinc supplementation on infections are conflicting, some studies do not find an effect of zinc supplementation in patients with infections, while other studies of healthy or institutionalized older adults, found that zinc supplementation significantly reduce the incidence of infections, antibiotic use and prevention of symptomatic COVID-19. Despite previous findings, the effect of zinc supplementation has not been studied in older acutely admitted medical patients on a large scale.
- Method This study is a cluster randomized controlled trail. A total of 8000 patients will be included and divided into three groups. Patients ≥ 65 years, who come to the Medical Emergency Department at Herlev Hospital, and who meet the inclusion criteria, will be offered participations in the study. An automatic pop-up in the patient medical record will appear in blocks of time and will randomly assign patients to intervention with zinc supplementation (intervention n = 1000), recommendation of zinc supplementation (recommendation n = 3000) or control (n = 4000), regardless of plasma zinc levels at admission. The treating doctor will assess if the patient is eligible and include the patient to the study. Measurements and collection of clinical data Date on readmissions and mortality will be collected from the electronic medical chart EPIC (Sundhedsplatformen). Data on prescribed antibiotics will be drawn from the Danish National Prescription Register. Antibiotic prescriptions within 15 days, will be considered as a single treatment, as described in a previous study. Research plan Project "ZOOM" will be included in a PhD programme. Inclusion is expected to start in February 2026. The inclusion period is anticipated to span 12 months, followed by a 12-month intervention period. Consequently, the intervention period ends in January 2028. Assessment of compliance To minimize waste of zinc supplements, patients in the intervention group will be contacted every 3 months, to assess further need of zinc supply, which will reflect the adherence of intervention.
- Statistical consideration
- Power calculation No available data exists to estimate the primary endpoint of Days Alive and Out of Hospital 12 months after acute hospitalization of older medical patients. However, a previous study that investigated this for patients with non-STEMI found a mean (SD) of 273 (123) days. Assuming that zinc supplementation can increase days alive and out of the hospital with 3% (8 days), we estimated a sample size of approximately 7422 patients (3712 in each arm), with an estimated power of 80%, 2-sided α-level of 0.05. Due to an estimated rate of loss to follow-up of approximately 10 %, we aim to enroll 8000 patients in the study. We plan to randomize participants into three groups: intervention, recommendation and control. However, the intervention and recommendation group will be considered as a single group for analysis. We plan to include patients during a 1-year study period. About 16.900 older patients (≥ 65 years) are hospitalized to the Medical Emergency Department, Herlev Hospital every year.
- Plan for statistical analysis of data Categorical variables will be compared using Chi-square test where appropriate; otherwise, Fisher's exact test will be used. Descriptive analyses of continuous variables will be per-formed using the Wilcoxon rank sum test. Binary outcomes will be analyzed by logistic re-gression and presented as odds ratios (ORs) and 95% confidence intervals (Cis). Overall sur-vival (OS) will be analyzed by the Kaplan Meier estimator; hazard ratios (HRs) and 95% CIs will be estimated by Cox proportional hazards regression. The primary endpoint (Days Alive and Out of Hospital) will be compared as a continuous variable between the two groups us-ing the analysis of variance test.
- Risks, adverse events and disadvantages
- Safety measures that minimize pain, discomfort, fear, and other risks All patients will receive standard treatment during and after hospitalization. The intervention group receives one capsule of 22 mg zinc sulfate once daily for 12 months. This dose is based on an assessment of achieving efficacy in reducing infections, improve immune function, while also being safe, with no serious adverse effects. The dose is far from the toxic zinc level of 1-2 grams per day, with no risk of serious adverse effects and below the U.S. Food and Drug Administration (40 mg/day). Adverse events of the zinc in doses around 22 mg daily are mild and most often consist of gastrointestinal symptoms (nausea, upset stomach, dizziness) and dry mouth. In a recent Cochrane review, it was not possible to distinguish between adverse events cause by zinc supplementation and events caused by the cold itself (e.g. headache). Chronic zinc toxicity leads to copper deficiency with bone marrow (granulocytopenia, sideroblastic anemia, myelodysplastic syndrome) and neurologic effects (ascending, sen-sorimotor polyneuropathy syndrome). Copper deficiency is the most serious adverse event of long-term zinc overdose. The daily zinc dose at 45 mg has previously been shown to be safe in a healthy cohort of older adults; by not reducing plasma-copper and at the same time the zinc supplementation significantly reduced the number of infections. Zinc is not considered being carcinogenic in general. A 30-year follow-up study showed that low zinc intake < 9mg/day may increase the risk of prostate cancer, whereas extremely high doses of > 75 mg/day and long-term supplementation could increase the risk of aggressive prostate cancer.
- Information from patient records We will not use medical records without consent. Specific information will be collected for implementation of the trial:
- Age, to evaluate if certain age-groups could benefit more from zinc supplementation than others.
- Results of routine blood parameters (CRP, neutrophils, leucocytes, platelets, hemoglobin, electrolytes, creatinine, eGFR, liver enzymes, lipids, HbA1c)
- Weight, height
- Demographic data
- Results of routinely assess Clinical Frailty Scale
- Disease history and the number of ICD-10 discharge diagnoses 5 years prior to admission, to assess comorbidity.
- Number of medications and type of medication at admission, to evaluate polypharmacy
- Length of hospitalization
- Readmission, cause and number of days admitted within 6 and 12 months
- Antibiotic use within 6 and 12 months
- Date of death and cause or day of follow-up if alive at 12 months after inclusion
- Processing of personal data in the project Data will be handled in accordance with The Data Protection Regulation and the Data Protection Act. The study is approved by the Danish National Medical Research Ethics Committee (VMK) and the Danish Data Protection Agency, before inclusion of patients. Data will be stored up to 5 years after end of study. Patient discontinuation Discontinuation may occur if the participant withdraws consent to participate in the study and/or withdraws consent for the use of their data. If a participant withdraws their consent, they will not be included in the study and their data will not be stored or analyzed. Information related to withdrawal will be obtained through "Sundhedsplatformen". The participant will be informed that they can withdrawal their consent at any time. Participants will receive a digital letter, two weeks after discharge, describing their participations in the study and informing them of their right to withdraw consent.
- Finances The study has received funding from the "Independent Research Fund Denmark", "Herlev and Gentofte Hospital Internal PhD Fellowship Funds", "Clinical Academic Groups", and "Novo Nordic Foundation". The investigators have no financial ties to the sponsor, or any other interests related to the trial.
- Recruitment of participants and informed consent
- Recruitment of participants This is a cluster randomized trial, in which each cluster consists of time. The treating doctor will assess if the patient is eligible (none of the exclusion criteria are present) and then include the patient.
- Publication and sharing data Results from the study, both negative, inconclusive, and positive, will be published in rele-vant peer-reviewed international scientific journals The investigators will be co-authors on all publications according to Vancouver guidelines. The project will be reported according to CONSORT guidelines and registered at www.clinicaltrials.gov before initiation.
- Patient insurance All participants are secured via the Danish Patient Compensation.
- Being tested
- Zinc (zinc sulphate)
- Keywords
- Older adults, Infections, Days alive and out of hospital, Zinc supplementation
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc (zinc sulphate)Dietary supplement
22 mg zinc sulphate tablets taken once daily for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | The intervention group will consist of 1000 patients who following discharge from the hospital will have daily zinc supplements prescribed and provided free of charge which will be sent to their home for a year. Receives: Dietary Supplement: Zinc (zinc sulphate) |
| Recommendation group | Experimental | The recommendation group will consist of 3000 patients who will have zinc supplements recommended and prescribed. However, zinc supplements will not be provided free of charge. Receives: Dietary Supplement: Zinc (zinc sulphate) |
| Control group | No intervention | The control group will consist of 4000 patients who will receive usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days Alive and Out of Hospital
To evaluate the differences between the groups in Days Alive and Out of Hospital. The endpoints will include date of death, date of hospitalization, and number of days hospitalized during the 12 months follow-up period in the three groups
Measured: During the 12 months follow-up period
Secondary outcomes (5)
Antibiotic use
Number of episodes with use of antibiotic
Measured: During the 12 months follow-up period
Hospital admissions
Number of hospital episodes of any cause
Measured: During the 12 months follow-up period
Readmission due to cardiovascular disease
Number of readmissions due to cardiovascular disease
Measured: During the 12 months follow-up period
Readmissions due to infections
Number of readmissions due to infections
Measured: During the 12 months follow-up period
Mortality
Number of deaths
Measured: During the 12 months follow-up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start1 Feb 2026
- Primary completion15 Mar 2028 (estimated)
- Study completion15 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Older Adults (65 Years and Older)Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is a cluster randomized controlled trial. Patients ≥ 65 years referred to the Medical Emergency Department at Herlev Hospital, and meet the inclusion criteria, will be randomized to participate in the study. Randomization In EPIC (Sundhedsplatformen) a generic module has been developed that facilitate cluster-level randomization directly in the system. In this study, clusters of time, will be used to randomly assign groups of patients to intervention with zinc supplementation (intervention n = 1000), recommendation of zinc supplementation (recommendation n = 3000), or usual care (control n = 4000). An automatic pop-up in EPIC (Sundhedsplatformen) will occur when a doctor opens the patients electronic medical chart. The randomization will occur based on unequal time windows with the same ratio of hours (8:6:2 hours) to ensure the anticipated segregation of 4:3:1. The time windows will be shifting an agreed number of minutes every day.
- Masking
- None (open label)
- Enrolment
- 8,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Independent Research Fund Denmark, The Novo Nordic Foundation
- Responsible party
- Principal investigator, Cecilia Margareta Lund, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07367412
- Sponsor's protocol ID
- ZOOM OUT
- Acronym
- ZOOM OUT
- Status last verified
- May 2026
- First submitted
- 16 Jan 2026
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson D, Vohra S, White IR, Boutron I. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025 Apr 14;389:e081123. doi: 10.1136/bmj-2024-081123.
PubMed 40228833European Parliament C of the EU. EU regulation No 536/2014 of the European parliaments and of the council of 16th of April 2014 on clinical trials on pharmaceutical products for human use article 30 (informed consent in cluster trials). http://data.europa.eu/eli/reg/2014/536/2022-12-05 2014
Zhang Y, Song M, Mucci LA, Giovannucci EL. Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study. Eur J Epidemiol. 2022 Dec;37(12):1251-1260. doi: 10.1007/s10654-022-00922-0. Epub 2022 Nov 3.
PubMed 36326979Porea TJ, Belmont JW, Mahoney DH Jr. Zinc-induced anemia and neutropenia in an adolescent. J Pediatr. 2000 May;136(5):688-90. doi: 10.1067/mpd.2000.103355.
PubMed 10802505Nault D, Machingo TA, Shipper AG, Antiporta DA, Hamel C, Nourouzpour S, Konstantinidis M, Phillips E, Lipski EA, Wieland LS. Zinc for prevention and treatment of the common cold. Cochrane Database Syst Rev. 2024 May 9;5(5):CD014914. doi: 10.1002/14651858.CD014914.pub2.
PubMed 38719213Silk R, LeFante C. Safety of zinc gluconate glycine (Cold-Eeze) in a geriatric population: a randomized, placebo-controlled, double-blind trial. Am J Ther. 2005 Nov-Dec;12(6):612-7. doi: 10.1097/01.mjt.0000179115.04316.18.
PubMed 16280656Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK222310/
PubMed 25057538Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health. 2010 Apr;7(4):1342-65. doi: 10.3390/ijerph7041342. Epub 2010 Mar 26.
PubMed 20617034Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D, Bao GW, Singh T, Cardozo LJ. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr. 2010 Jun;91(6):1634-41. doi: 10.3945/ajcn.2009.28836. Epub 2010 Apr 28.
PubMed 20427734Intorre F, Polito A, Andriollo-Sanchez M, Azzini E, Raguzzini A, Toti E, Zaccaria M, Catasta G, Meunier N, Ducros V, O'Connor JM, Coudray C, Roussel AM, Maiani G. Effect of zinc supplementation on vitamin status of middle-aged and older European adults: the ZENITH study. Eur J Clin Nutr. 2008 Oct;62(10):1215-23. doi: 10.1038/sj.ejcn.1602844. Epub 2007 Jul 11.
PubMed 17622255Duncan A, Morrison I, Bryson S. Iatrogenic copper deficiency: Risks and cautions with zinc prescribing. Br J Clin Pharmacol. 2023 Sep;89(9):2825-2829. doi: 10.1111/bcp.15749. Epub 2023 May 25.
PubMed 37070154Prasad AS. Essentiality and toxicity of zinc. Scand J Work Environ Health. 1993;19 Suppl 1:134-6. No abstract available.
PubMed 8159965Boukaiba N, Flament C, Acher S, Chappuis P, Piau A, Fusselier M, Dardenne M, Lemonnier D. A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population. Am J Clin Nutr. 1993 Apr;57(4):566-72. doi: 10.1093/ajcn/57.4.566.
PubMed 8460613Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Herchberg S. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med. 1999 Apr 12;159(7):748-54. doi: 10.1001/archinte.159.7.748.
PubMed 10218756Sanchis J, Bueno H, Minana G, Guerrero C, Marti D, Martinez-Selles M, Dominguez-Perez L, Diez-Villanueva P, Barrabes JA, Marin F, Villa A, Sanmartin M, Llibre C, Sionis A, Carol A, Garcia-Blas S, Calvo E, Morales Gallardo MJ, Elizaga J, Gomez-Blazquez I, Alfonso F, Garcia Del Blanco B, Nunez J, Formiga F, Ariza-Sole A. Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA Intern Med. 2023 May 1;183(5):407-415. doi: 10.1001/jamainternmed.2023.0047.
PubMed 36877502
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Zinc Supplementation on Occurrence of Infections in Older Medical Patients (ZOOM) - a Cluster Randomized Controlled Trial (ZOOM OUT).
- ClinicalTrials.gov ID
- NCT07367412
- Acronym / sponsor ID
- ZOOM OUT / ZOOM OUT
- Keywords
- Older adults, Infections, Days alive and out of hospital, Zinc supplementation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 8,000 participants (estimated)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Independent Research Fund Denmark, The Novo Nordic Foundation
- Study start
- 1 Feb 2026 (actual)
- Primary completion
- 15 Mar 2028 (estimated)
- Study completion
- 15 Mar 2028 (estimated)
- First posted
- 26 Jan 2026 (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.
The goal of this clinical trial is to learn about the effect of zinc supplementation once daily for 12 months in older acute medical patients. The main question it aims to answer is:
- Can daily zinc supplementation for 12 months increase Days Alive and Out of Hospital (DAOH)? Researchers will compare zinc supplementation to a control group, a group who do not receive zinc supplementation, to see if zinc supplementation can increase Days Alive and Out of Hospital, reduce antibiotic use, readmissions and mortality.
Participants will take 22 mg zinc supplementation once daily for 12 months or not.
The researchers will draw data on readmissions, antibiotic use and mortality during the 12 months follow-up period.
Detailed description
- Study purpose Older adults are at increased risk of micronutrient deficiencies, including zinc, due to sparse food intake. Zinc deficiency is known to increase the susceptibility to infections, further exacerbating the vulnerability of older adults to health complications. Infections are common among older adults and are a leading causes of acute hospital admissions and readmissions. The hypothesis is that zinc supplementation for older acutely admitted medical patients can increase Days Alive and Out of Hospital regardless of baseline plasma zinc level Objectives: Primary objective: To test in older acute medical patients if zinc supplementation once daily for 12 months can increase Days Alive and Out of Hospital. Secondary objectives: To evaluate if zinc supplementation once daily can reduce antibiotic use, readmissions and mortality during the 12 months follow-up period.
- Short background A large proportion of older adults are malnourished, which can lead to increased morbidity, mortality, prolonged hospitalization and reduced quality of life (QoL). With malnutrition the patient lacks vitamins and minerals, including zinc, which is essential for older adults. Early detection and treatment of malnutrition has been shown to be beneficial for patients, including reducing length of stay in the hospital. The older adults are at increased risk of zinc deficiency, with less than half of the free-living older adults having a sufficient zinc intake. Zinc is essential for immune function and acute deficiency weakens both innate and adaptive immunity, increasing susceptibility to infections. The effects of zinc supplementation on infections are conflicting, some studies do not find an effect of zinc supplementation in patients with infections, while other studies of healthy or institutionalized older adults, found that zinc supplementation significantly reduce the incidence of infections, antibiotic use and prevention of symptomatic COVID-19. Despite previous findings, the effect of zinc supplementation has not been studied in older acutely admitted medical patients on a large scale.
- Method This study is a cluster randomized controlled trail. A total of 8000 patients will be included and divided into three groups. Patients ≥ 65 years, who come to the Medical Emergency Department at Herlev Hospital, and who meet the inclusion criteria, will be offered participations in the study. An automatic pop-up in the patient medical record will appear in blocks of time and will randomly assign patients to intervention with zinc supplementation (intervention n = 1000), recommendation of zinc supplementation (recommendation n = 3000) or control (n = 4000), regardless of plasma zinc levels at admission. The treating doctor will assess if the patient is eligible and include the patient to the study. Measurements and collection of clinical data Date on readmissions and mortality will be collected from the electronic medical chart EPIC (Sundhedsplatformen). Data on prescribed antibiotics will be drawn from the Danish National Prescription Register. Antibiotic prescriptions within 15 days, will be considered as a single treatment, as described in a previous study. Research plan Project "ZOOM" will be included in a PhD programme. Inclusion is expected to start in February 2026. The inclusion period is anticipated to span 12 months, followed by a 12-month intervention period. Consequently, the intervention period ends in January 2028. Assessment of compliance To minimize waste of zinc supplements, patients in the intervention group will be contacted every 3 months, to assess further need of zinc supply, which will reflect the adherence of intervention.
- Statistical consideration
- Power calculation No available data exists to estimate the primary endpoint of Days Alive and Out of Hospital 12 months after acute hospitalization of older medical patients. However, a previous study that investigated this for patients with non-STEMI found a mean (SD) of 273 (123) days. Assuming that zinc supplementation can increase days alive and out of the hospital with 3% (8 days), we estimated a sample size of approximately 7422 patients (3712 in each arm), with an estimated power of 80%, 2-sided α-level of 0.05. Due to an estimated rate of loss to follow-up of approximately 10 %, we aim to enroll 8000 patients in the study. We plan to randomize participants into three groups: intervention, recommendation and control. However, the intervention and recommendation group will be considered as a single group for analysis. We plan to include patients during a 1-year study period. About 16.900 older patients (≥ 65 years) are hospitalized to the Medical Emergency Department, Herlev Hospital every year.
- Plan for statistical analysis of data Categorical variables will be compared using Chi-square test where appropriate; otherwise, Fisher's exact test will be used. Descriptive analyses of continuous variables will be per-formed using the Wilcoxon rank sum test. Binary outcomes will be analyzed by logistic re-gression and presented as odds ratios (ORs) and 95% confidence intervals (Cis). Overall sur-vival (OS) will be analyzed by the Kaplan Meier estimator; hazard ratios (HRs) and 95% CIs will be estimated by Cox proportional hazards regression. The primary endpoint (Days Alive and Out of Hospital) will be compared as a continuous variable between the two groups us-ing the analysis of variance test.
- Risks, adverse events and disadvantages
- Safety measures that minimize pain, discomfort, fear, and other risks All patients will receive standard treatment during and after hospitalization. The intervention group receives one capsule of 22 mg zinc sulfate once daily for 12 months. This dose is based on an assessment of achieving efficacy in reducing infections, improve immune function, while also being safe, with no serious adverse effects. The dose is far from the toxic zinc level of 1-2 grams per day, with no risk of serious adverse effects and below the U.S. Food and Drug Administration (40 mg/day). Adverse events of the zinc in doses around 22 mg daily are mild and most often consist of gastrointestinal symptoms (nausea, upset stomach, dizziness) and dry mouth. In a recent Cochrane review, it was not possible to distinguish between adverse events cause by zinc supplementation and events caused by the cold itself (e.g. headache). Chronic zinc toxicity leads to copper deficiency with bone marrow (granulocytopenia, sideroblastic anemia, myelodysplastic syndrome) and neurologic effects (ascending, sen-sorimotor polyneuropathy syndrome). Copper deficiency is the most serious adverse event of long-term zinc overdose. The daily zinc dose at 45 mg has previously been shown to be safe in a healthy cohort of older adults; by not reducing plasma-copper and at the same time the zinc supplementation significantly reduced the number of infections. Zinc is not considered being carcinogenic in general. A 30-year follow-up study showed that low zinc intake < 9mg/day may increase the risk of prostate cancer, whereas extremely high doses of > 75 mg/day and long-term supplementation could increase the risk of aggressive prostate cancer.
- Information from patient records We will not use medical records without consent. Specific information will be collected for implementation of the trial:
- Age, to evaluate if certain age-groups could benefit more from zinc supplementation than others.
- Results of routine blood parameters (CRP, neutrophils, leucocytes, platelets, hemoglobin, electrolytes, creatinine, eGFR, liver enzymes, lipids, HbA1c)
- Weight, height
- Demographic data
- Results of routinely assess Clinical Frailty Scale
- Disease history and the number of ICD-10 discharge diagnoses 5 years prior to admission, to assess comorbidity.
- Number of medications and type of medication at admission, to evaluate polypharmacy
- Length of hospitalization
- Readmission, cause and number of days admitted within 6 and 12 months
- Antibiotic use within 6 and 12 months
- Date of death and cause or day of follow-up if alive at 12 months after inclusion
- Processing of personal data in the project Data will be handled in accordance with The Data Protection Regulation and the Data Protection Act. The study is approved by the Danish National Medical Research Ethics Committee (VMK) and the Danish Data Protection Agency, before inclusion of patients. Data will be stored up to 5 years after end of study. Patient discontinuation Discontinuation may occur if the participant withdraws consent to participate in the study and/or withdraws consent for the use of their data. If a participant withdraws their consent, they will not be included in the study and their data will not be stored or analyzed. Information related to withdrawal will be obtained through "Sundhedsplatformen". The participant will be informed that they can withdrawal their consent at any time. Participants will receive a digital letter, two weeks after discharge, describing their participations in the study and informing them of their right to withdraw consent.
- Finances The study has received funding from the "Independent Research Fund Denmark", "Herlev and Gentofte Hospital Internal PhD Fellowship Funds", "Clinical Academic Groups", and "Novo Nordic Foundation". The investigators have no financial ties to the sponsor, or any other interests related to the trial.
- Recruitment of participants and informed consent
- Recruitment of participants This is a cluster randomized trial, in which each cluster consists of time. The treating doctor will assess if the patient is eligible (none of the exclusion criteria are present) and then include the patient.
- Publication and sharing data Results from the study, both negative, inconclusive, and positive, will be published in rele-vant peer-reviewed international scientific journals The investigators will be co-authors on all publications according to Vancouver guidelines. The project will be reported according to CONSORT guidelines and registered at www.clinicaltrials.gov before initiation.
- Patient insurance All participants are secured via the Danish Patient Compensation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study is a cluster randomized controlled trial. Patients ≥ 65 years referred to the Medical Emergency Department at Herlev Hospital, and meet the inclusion criteria, will be randomized to participate in the study. Randomization In EPIC (Sundhedsplatformen) a generic module has been developed that facilitate cluster-level randomization directly in the system. In this study, clusters of time, will be used to randomly assign groups of patients to intervention with zinc supplementation (intervention n = 1000), recommendation of zinc supplementation (recommendation n = 3000), or usual care (control n = 4000). An automatic pop-up in EPIC (Sundhedsplatformen) will occur when a doctor opens the patients electronic medical chart. The randomization will occur based on unequal time windows with the same ratio of hours (8:6:2 hours) to ensure the anticipated segregation of 4:3:1. The time windows will be shifting an agreed number of minutes every day.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Dietary Supplement: Zinc (zinc sulphate)The intervention group will consist of 1000 patients who following discharge from the hospital will have daily zinc supplements prescribed and provided free of charge which will be sent to their home for a year. |
| Recommendation group | Experimental | Dietary Supplement: Zinc (zinc sulphate)The recommendation group will consist of 3000 patients who will have zinc supplements recommended and prescribed. However, zinc supplements will not be provided free of charge. |
| Control group | No intervention | –The control group will consist of 4000 patients who will receive usual care |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- All medical patients aged ≥ 65 years assessed at the Medical Emergency Department, Herlev Hospital
Key exclusion criteria (6 listed)
- Self-supplementing with zinc at time of assessment (> 10 mg zinc/day)
- Terminal illness (life expectancy < 6 months, estimated by Clinical Frailty Scale ≥8)
- Patients receiving parenteral nutrition (partial or complete)
- Patients treated with hemodialysis or peritoneal dialysis
- Patients know with known severe dementia
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 |
|---|---|---|
| Zinc (zinc sulphate)22 mg zinc sulphate tablets taken once daily for 12 months | Dietary supplement | Intervention, Recommendation group |
Primary outcome
Days Alive and Out of Hospital
Time frame: During the 12 months follow-up period
To evaluate the differences between the groups in Days Alive and Out of Hospital. The endpoints will include date of death, date of hospitalization, and number of days hospitalized during the 12 months follow-up period in the three groups
5 secondary outcomes
Antibiotic use
Time frame: During the 12 months follow-up period
Hospital admissions
Time frame: During the 12 months follow-up period
Readmission due to cardiovascular disease
Time frame: During the 12 months follow-up period
Readmissions due to infections
Time frame: During the 12 months follow-up period
Mortality
Time frame: During the 12 months follow-up period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Background: PubMed 40228833Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson D, Vohra S, White IR, Boutron I. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025 Apr 14;389:e081123. doi: 10.1136/bmj-2024-081123.
- BackgroundEuropean Parliament C of the EU. EU regulation No 536/2014 of the European parliaments and of the council of 16th of April 2014 on clinical trials on pharmaceutical products for human use article 30 (informed consent in cluster trials). http://data.europa.eu/eli/reg/2014/536/2022-12-05 2014
- Background: PubMed 36326979Zhang Y, Song M, Mucci LA, Giovannucci EL. Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study. Eur J Epidemiol. 2022 Dec;37(12):1251-1260. doi: 10.1007/s10654-022-00922-0. Epub 2022 Nov 3.
- Background: PubMed 10802505Porea TJ, Belmont JW, Mahoney DH Jr. Zinc-induced anemia and neutropenia in an adolescent. J Pediatr. 2000 May;136(5):688-90. doi: 10.1067/mpd.2000.103355.
- Background: PubMed 38719213Nault D, Machingo TA, Shipper AG, Antiporta DA, Hamel C, Nourouzpour S, Konstantinidis M, Phillips E, Lipski EA, Wieland LS. Zinc for prevention and treatment of the common cold. Cochrane Database Syst Rev. 2024 May 9;5(5):CD014914. doi: 10.1002/14651858.CD014914.pub2.
- Background: PubMed 16280656Silk R, LeFante C. Safety of zinc gluconate glycine (Cold-Eeze) in a geriatric population: a randomized, placebo-controlled, double-blind trial. Am J Ther. 2005 Nov-Dec;12(6):612-7. doi: 10.1097/01.mjt.0000179115.04316.18.
- Background: PubMed 25057538Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK222310/
- Background: PubMed 20617034Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health. 2010 Apr;7(4):1342-65. doi: 10.3390/ijerph7041342. Epub 2010 Mar 26.
- Background: PubMed 20427734Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D, Bao GW, Singh T, Cardozo LJ. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr. 2010 Jun;91(6):1634-41. doi: 10.3945/ajcn.2009.28836. Epub 2010 Apr 28.
- Background: PubMed 17622255Intorre F, Polito A, Andriollo-Sanchez M, Azzini E, Raguzzini A, Toti E, Zaccaria M, Catasta G, Meunier N, Ducros V, O'Connor JM, Coudray C, Roussel AM, Maiani G. Effect of zinc supplementation on vitamin status of middle-aged and older European adults: the ZENITH study. Eur J Clin Nutr. 2008 Oct;62(10):1215-23. doi: 10.1038/sj.ejcn.1602844. Epub 2007 Jul 11.
- Background: PubMed 37070154Duncan A, Morrison I, Bryson S. Iatrogenic copper deficiency: Risks and cautions with zinc prescribing. Br J Clin Pharmacol. 2023 Sep;89(9):2825-2829. doi: 10.1111/bcp.15749. Epub 2023 May 25.
- Background: PubMed 8159965Prasad AS. Essentiality and toxicity of zinc. Scand J Work Environ Health. 1993;19 Suppl 1:134-6. No abstract available.
- Individual participant dataSharing planned: Yes
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zinc (zinc sulphate) in people with Older Adults (65 Years and Older) and Medical Patients in the Emergency Department, run by Herlev Hospital at 2 sites in Denmark.
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 1 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 29 May 2026. 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 Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cecilia M Lund, Senior consultant, PhD (+45 38686112, cecilia.margareta.lund@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days Alive and Out of Hospital (time frame: During the 12 months follow-up period). 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 NCT07367412, which also lists 35 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 29 May 2026.