key: cord-0828445-x9r74q3e
authors: Ziaei, Ava; Davoodian, Parivash; Dadvand, Habib; Safa, Omid; Hassanipour, Soheil; Omidi, Mahmoud; Masjedi, Moein; Mahmoudikia, Fahime; Rafiee, Bahareh; Fathalipour, Mohammad
title: Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial
date: 2020-10-26
journal: Trials
DOI: 10.1186/s13063-020-04737-w
sha: 2adae332d4be152f8d83166bbde90a44f82da80e
doc_id: 828445
cord_uid: x9r74q3e

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. Inclusion criteria: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. 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 capsules at a dose of 50 mg daily for a period of seven days. Control group: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1β (IL-1β), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions 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 10 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): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N5”. The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.

‫مالتونین‬ ( N - ‫استیل‬ - 0 - ‫متیوکسی‬ ‫تریپتامین‬ ) ‫یک‬ ‫مولکول‬ ‫فعال‬ ‫زیستی‬ ‫با‬ ‫مجموعه‬ ‫ای‬ ‫از‬ ‫خواص‬ ‫تقویت‬ ‫کن‬ ‫نده‬ ‫سالمتی‬ ‫است‬ . ‫مالتونین‬ ‫با‬ ‫موفقیت‬ ‫در‬ ‫درمان‬ ‫اختالالت‬ ‫خواب‬ ، ‫دلیریوم‬ ، ‫آترواسکلروز‬ ، ‫بیماری‬ ‫تنفسی‬ ‫و‬ ‫عفونت‬ ‫های‬ ‫ویروسی‬ ‫مورد‬ ‫استفاده‬ ‫قرار‬ ‫گرفته‬ ‫است‬ [ 01 .] ‫تحقیقات‬ ‫قبلی‬ ‫اثرات‬ ‫مثبت‬ ‫مالتونین‬ ‫را‬ ‫در‬ ‫کاهش‬ ‫استرس‬ ‫حاد‬ ‫تنفسی‬ ‫ناشی‬ ‫از‬ ‫ویروس‬ ، ‫باکتریها‬ ، ‫پرتودرمانی‬ ‫و‬ ‫غیره‬ ‫را‬ ‫مستند‬ ‫کرده‬ ‫است‬ [ 00 - 03 .] ‫در‬ ‫شرایط‬ ‫مزمن‬ ‫مانند‬ ‫دیابت‬ ‫و‬ ‫مولتیپل‬ ‫اسکلروز‬ ‫مصرف‬ ‫مالتونین‬ ‫به‬ ‫ترتیب‬ ‫به‬ ‫مدت‬ 8 ‫هفته‬ ‫و‬ 0 ‫ماه‬ ‫به‬ ‫طور‬ ‫قابل‬ ‫توجهی‬ ‫سطح‬ ‫سرمی‬ TNF-α ، IL-6 ، IL-1β ‫و‬ CRP ‫را‬ ‫کاهش‬ ‫داده‬ ‫است‬ [ 00 6 00 .] ‫در‬ ‫شرایط‬ ‫حاد‬ ‫مانند‬ ‫استرس‬ ‫جراحی‬ ، ‫خونرسانی‬ ‫مجدد‬ ‫مغز‬ ‫و‬ ‫خونرسانی‬ ‫مجدد‬ ‫شریان‬ ‫کرونر‬ ‫استفاده‬ ‫روزانه‬ ‫از‬ ‫داروی‬ ‫خوراکی‬ ‫مالتونین‬ 01 mg / d ، 6mg / d ‫و‬ 0 mg / d ‫به‬ ‫ترتیب‬ ‫به‬ ‫طور‬ ‫قابل‬ ‫توجهی‬ ‫سطح‬ ‫سرمی‬ ‫سیتوکین‬ ‫های‬ ‫التهابی‬ ‫را‬ ‫کاهش‬ ‫می‬ ‫دهد‬ [ 00 - 08 .] ‫همانطور‬ ‫که‬ ً ‫قبال‬ ‫مورد‬ ‫بررسی‬ ‫قرار‬ ‫گرفت‬ ، ‫استفاده‬ ‫کوتاه‬ ‫مدت‬ ‫از‬ ‫مالتونین‬ ‫بی‬ ‫خطر‬ ‫است‬ ، ‫حتی‬ ‫در‬ ‫موارد‬ ‫مص‬ ‫رف‬ 7 ‫زیاد‬ ، ‫و‬ ‫عوارض‬ ‫جانبی‬ ‫گزارش‬ ‫شده‬ ‫محدود‬ ‫به‬ ‫سرگیجه‬ ، ‫سردرد‬ ، ‫حالت‬ ‫تهوع‬ ‫و‬ ‫خواب‬ ‫آلودگی‬ ‫هستند‬ . ‫به‬ ‫طور‬ ‫کلی‬ ‫ایمنی‬ ‫مالتونین‬ ‫در‬ ‫انسان‬ ‫بسیار‬ ‫باال‬ ‫است‬ [ 02 .] ‫در‬ ‫آزمایشات‬ ‫بالینی‬ ، ‫دوزهای‬ 3 ‫میلی‬ ‫گرم‬ ، 0 ‫میلی‬ ‫گرم‬ ‫و‬ 01 ‫میلی‬ ‫گرم‬ ‫خوراکی‬ ‫مالتونین‬ ‫خوراکی‬ ‫توسط‬ ‫بیماران‬ ‫در‬ ‫بخش‬ ‫مراقبت‬ ‫های‬ ‫ویژه‬ ، ‫در‬ ‫مقایسه‬ ‫با‬ ‫دارونما‬ ، ‫ا‬ ‫یمنی‬ ‫رضایت‬ ‫بخش‬ ‫نشان‬ ‫داد‬ [ 2 .] ‫همچنین‬ ، ‫حتی‬ ‫وقتی‬ ‫مالتونین‬ ‫به‬ ‫مدت‬ ‫دو‬ ‫ماه‬ ‫به‬ ‫میزان‬ 0 ‫گرم‬ ‫در‬ ‫روز‬ ‫به‬ ‫انسان‬ ‫تجویز‬ ‫شد‬ ، ‫هیچ‬ ‫گزارش‬ ‫نامطلوبی‬ ‫از‬ ‫درمان‬ ‫گزارش‬ ‫نشده‬ ‫است‬ [ 91 .] ‫سرانجام‬ ، ‫هیچ‬ ‫عارضه‬ ‫جانبی‬ ‫پس‬ ‫از‬ ‫استفاده‬ ‫از‬ ‫مالتونین‬ ‫در‬ ‫مطالعات‬ ‫حیوانی‬ ALI / ARDS ‫ثبت‬ ‫نشده‬ ‫است‬ [ 2 .] ‫به‬ ‫همین‬ ‫ترتیب‬ ‫و‬ ‫با‬ ‫توجه‬ ‫به‬ ‫عدم‬ ‫وجود‬ ‫یک‬ ‫کارآزمایی‬ ‫بالینی‬ ‫در‬ ‫مورد‬ ‫تأثیر‬ ‫مالتونین‬ ‫بر‬ ‫بیماران‬ covid-19 ، ‫تصمیم‬ ‫به‬ ‫اجرای‬ ‫این‬ ‫کارآزمایی‬ ‫در‬ ‫بیمارستان‬ ‫شهید‬ ‫محمدی‬ ‫بندرعباس،‬ ‫هرمزگان،‬ ‫ایران‬ ‫گرفتیم‬ . 8 ‫متون‬ ‫بررسی‬ ‫معمول‬ ‫تظاهرات‬ COVID-19 ‫میالژی‬ ، ‫چشایی‬ ‫در‬ ‫اختالل‬ ‫و‬ ‫بو‬ ، ‫اشتهایی‬ ‫بی‬ ، ‫خستگی‬ ، ‫خشک‬ ‫سرفه‬ ، ‫تب‬ ‫شامل‬ ‫تظاهرات‬ ‫و‬ ‫گلودرد‬ ، ‫اسهال‬ ، ‫تهوع‬ ‫حالت‬ ، ‫سردرد‬ ، ‫بینی‬IL-1β ، IL-2 ، IL-6 ، IL-8 ‫را‬ ‫نشان‬ ‫می‬ ‫دهند‬ ، ‫هر‬ ‫دو‬ IFN-α / β ، TNF ‫موتیف‬ ، ‫کموکاین‬ 3 (CCL3) ، CCL5 ، CCL2 ‫و‬ IP-

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