Clinical trial NCT04353128: Efficacy of Melatonin in the Prophylaxis of Coronavirus Disease 2019 (COVID-19) Among Healthcare Workers.
Official title: Multicenter Randomized Controlled Trial of the Efficacy of Melatonin in the Prophylaxis of SARS-coronavirus-2 Infection Among High Risk Contacts.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
SARS-CoV 2
Coronavirus Infection
Keywords: melatonin
prevention
covid19
Sars-CoV2
healthcare
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: SARS-CoV 2 infection rate
timeFrame: up to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Hospital Universitario La Paz
name: Pedro de la Oliva, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Antonio J Carcas
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Irene García García
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Amelia Rodríguez Mariblanca
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Lucía Martínez de Soto
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: María J Rosales
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: José R Arribas
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Juan González
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Alberto M Borobia, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Universitario La Paz
name: Miguel Rodriguez-Rubio, MD
role: STUDY_CHAIR
References:
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