Evaluation of the effect of melatonin in patients with COVID-19-induced pneumonia admitted to the Intensive Care Unit: A structured summary of a study protocol for a randomized controlled trial

Abstract

Objectives We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). Trial design This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding Intervention and Comparator Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education’s protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education’s protocol for a period of seven days. Main outcomes The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. Randomization Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. Trial registration The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N7”. The registration date was February 16, 2021. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Efficacy of melatonin in the treatment of patients with COVID‐19: A systematic review and meta‐analysis of randomized controlled trials

“…Additional large‐scale RCTs are required to validate our findings; currently, several ongoing RCTs are investigating the usefulness of melatonin as a treatment for patients with COVID‐19 in both the ICU and in outpatient departments. 22 , 23 , 24 , 25 Although there were some differences in study design between the three included RCTs, 12 , 13 , 14 all the outcome analyses in this study demonstrated low heterogeneity, which might minimize the confounding effect of heterogeneity. Melatonin is used to treat circadian rhythm sleep‐wake disorders and insomnia; however, in this study, we did not evaluate its effect on the sleep quality of patients with COVID‐19.…”

Analysis of the Incidence and Risk Factors of Precocious Puberty in Girls during the COVID-19 Pandemic

“…It is used to treat sleep disorders [32], is an antioxidant, and has anti-inflammatory and immunomodulatory effects on many diseases [33][34][35][36]. MT has been used for patients with severe coronary pneumonia during the COVID-19 pandemic [37].…”

“…It is used to treat sleep disorders [ 32 ], is an antioxidant, and has anti-inflammatory and immunomodulatory effects on many diseases [ 33 – 36 ]. MT has been used for patients with severe coronary pneumonia during the COVID-19 pandemic [ 37 ]. Although multiple short-term and long-term randomized, double-blind, controlled trials have confirmed that an oral dose of MT within the range of 2–10 mg/day is safe for children and adolescents [ 38 ], further studies are required to determine whether MT can be used for the prevention of PP.…”

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy

“…Currently, there are no published results from a clinical trial using melatonin as a treatment for COVID-19; however, our search provided two protocols for double blind, randomized clinical trials utilizing melatonin dosages of 5mg twice daily by oral capsule for 7 days ( 58 ) and 5mg per kg of bodyweight intravenous every 6 hours for 7 days ( 59 ). In addition, clinicaltrials.gov currently lists 6 ongoing studies (NCT04474483, NCT04784754, NCT04409522, NCT04530539, NCT04353128, NCT04470297) using melatonin as treatment in COVID-19 patients for both intensive care unit patients and outpatients ( 60 , 61 , 62 , 63 , 64 , 65 ).…”