Efficacy of Melatonin in the Prophylaxis of Coronavirus Disease 2019 (COVID-19) Among Healthcare Workers.

Covid19 Clinical Trial

— MeCOVID  

Official title:

Multicenter Randomized Controlled Trial of the Efficacy of Melatonin in the Prophylaxis of SARS-coronavirus-2 Infection Among High Risk Contacts.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04353128
• Other study ID #: MeCOVID
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 20, 2020
• Est. completion date: December 1, 2020

Study information

• Verified date: April 2020
• Source: Instituto de Investigación Hospital Universitario La Paz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is an urgent need to evaluate interventions that can prevent the infection with SARS-CoV 2 of healthcare workers at risk. Melatonin is an inexpensive and safe product with protective effect in both bacterial and viral infections likely due to its anti-inflammatory and anti-oxidative effects. This randomized controlled trial seeks to evaluate is efficacy as a prophylaxis in healthcare workers exposed to the virus in their clinical practice.

Description:

Healthcare workers are at an increased risk of acquiring COVID-19 due to an increased exposure to the virus and global personal protective equipment shortages. Preventing the infection of healthcare workers is critical the current epidemic situation when healthcare systems are under extreme pressure. There is a lack of evidence surrounding potential preventive strategies to decrease the incidence of COVID-19 among healthcare workers.

Melatonin, an endogenous hormone involved in circadian rhythm control, is an inexpensive and safe product that has shown protective effects in bacterial and viral infections likely due to its anti-inflammatory and anti-oxidative effects.

SARS-CoV 2 seems to relatively spare younger children and those who are infected develop the severe forms of the disease very rarely. Peak melatonin serum levels are higher in younger children and decrease with age. These levels are also higher in women, specially during pregnancy, who also seem to be less affected by the virus when compared to men.

The investigators hypothesize that elevating peak melatonin levels to a range similar to that of children by administering 2 mg of melatonin daily might prevent the infection with SARS-CoV 2 among exposed healthcare workers. The investigators also hypothesize that among those who develop the disease melatonin might prevent the more severe forms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: December 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection

• Not having a previous COVID19 diagnosis

• Not having experienced COVID19 symptoms from March 1st 2020 until randomization

• Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until randomization

• Having a negative SARS-CoV 2 CRP before randomization

• Having a negative urinary pregnancy test in the previous 7 days for premenopausal women

• Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method

Exclusion Criteria:

• HIV infection

• Active hepatitis B infection

• Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis

• Osteoporosis

• Myasthenia gravis

• Retinitis pigmentosa

• Bradycardia (less than 50 bpm)

• Weight less than 40 Kg

• Treatment with drugs that prolong the QT interval for more than 7 days in the last month before randomization including: azithromycin, cisapride, methadone, droperidol, sotalol, quinidine, clarithromycin, haloperidol...

• Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption

• Treatment with fluvoxamine

• Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon

• Pregnancy

• Breastfeeding

• History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis

• Insulin-dependent diabetes mellitus

• Known history of hypersensitivity to the study drug or any of its components

• Patients that should not be included in the study at the judgment of the research team

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Infections
• SARS-CoV 2

Intervention

Drug:
• Melatonin 2mg
2 mg of prolonged release melatonin tablets per os (P.O.) before bedtime for 12 weeks
• Placebo oral tablet
Identically looking placebo tablets P.O. before bedtime for 12 weeks

Locations

Country	Name	City	State
Spain	Hospital Universitario La Paz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigación Hospital Universitario La Paz

Country where clinical trial is conducted

Spain, 

References & Publications (9)

Gooneratne NS, Edwards AY, Zhou C, Cuellar N, Grandner MA, Barrett JS. Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. J Pineal Res. 2012 May;52(4):437-45. doi: 10.1111/j.1600-079X.2011.00958.x. Epub 2012 Feb 21. — View Citation

Gunn PJ, Middleton B, Davies SK, Revell VL, Skene DJ. Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions. Chronobiol Int. 2016;33(1):39-50. doi: 10.3109/07420528.2015.1112396. Epub 2016 Jan 5. — View Citation

Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020 Jun;53(3):371-372. doi: 10.1016/j.jmii.2020.02.011. Epub 2020 Feb 25. — View Citation

Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr 23;382(17):1663-1665. doi: 10.1056/NEJMc2005073. Epub 2020 Mar 18. — View Citation

Ran L, Chen X, Wang Y, Wu W, Zhang L, Tan X. Risk Factors of Healthcare Workers With Coronavirus Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China. Clin Infect Dis. 2020 Nov 19;71(16):2218-2221. doi: 10.1093/cid/ciaa287. — View Citation

Scholtens RM, van Munster BC, van Kempen MF, de Rooij SE. Physiological melatonin levels in healthy older people: A systematic review. J Psychosom Res. 2016 Jul;86:20-7. doi: 10.1016/j.jpsychores.2016.05.005. Epub 2016 May 10. Review. — View Citation

Tan DX, Korkmaz A, Reiter RJ, Manchester LC. Ebola virus disease: potential use of melatonin as a treatment. J Pineal Res. 2014 Nov;57(4):381-4. doi: 10.1111/jpi.12186. Epub 2014 Oct 14. Review. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. — View Citation

Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020 Jun 1;250:117583. doi: 10.1016/j.lfs.2020.117583. Epub 2020 Mar 23. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SARS-CoV 2 infection rate	Number of confirmed (positive CRP) symptomatic infections in each treatment group	up to 12 weeks