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High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial

Alizadeh et al., Journal of Taibah University Medical Sciences, doi:10.1016/j.jtumed.2022.04.012
May 2022  
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Mortality 4% Improvement Relative Risk Extubation 14% Ventilation time 27% Melatonin  Alizadeh et al.  INTUBATED PATIENTS  DB RCT Is very late treatment with melatonin beneficial for COVID-19? Double-blind RCT 67 patients in Iran (June - September 2020) Improved recovery (p=0.19) and shorter ventilation (p=0.091), not sig. c19early.org Alizadeh et al., J. Taibah University .., May 2022 Favorsmelatonin Favorscontrol 0 0.5 1 1.5 2+
Melatonin for COVID-19
11th treatment shown to reduce risk in December 2020, now with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.
This study is excluded in the after exclusion results of meta analysis: extremely late treatment, over 75% control mortality.
risk of death, 3.8% lower, RR 0.96, p = 0.73, treatment 28 of 33 (84.8%), control 30 of 34 (88.2%), NNT 30.
risk of no extubation, 13.6% lower, RR 0.86, p = 0.19, treatment 26 of 33 (78.8%), control 31 of 34 (91.2%), NNT 8.1.
ventilation time, 27.0% lower, relative time 0.73, p = 0.09, treatment 33, control 34.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Alizadeh et al., 13 May 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 11 authors, study period June 2020 - September 2020. Contact: h-hosami@sina.tums.ac.ir.
This PaperMelatoninAll
Abstract: JTUMED916_proof ■ 13 May 2022 ■ 1/7 Journal of Taibah University Medical Sciences (xxxx) xxx(xxx), xxx Taibah University Journal of Taibah University Medical Sciences www.sciencedirect.com 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Original Article High dose melatonin as an adjuvant therapy in intubated patients with Q2 COVID-19: A randomized clinical trial Nafiseh Alizadeh a, Mehrnoush Dianatkhah b, Yousef Alimohamadi c, Hazhir Moradi d, Samaneh Akbarpour e, Majid Akrami f, Fariba Mansouri g, Neda Faraji g, Zahra Rezaie h, i i, Q3 Mahboubeh Alizadeh and Hadiseh Hosamirudsari * Q18 a Department of Pharmaceutical Care, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran Department of Clinical Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran c Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Q4 d Medical School, Isfahan University of Medical Sciences, Isfahan, Iran Q5 e Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran f Department of Anesthesiology, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran g Department of Internal Medicine, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran h Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran i Department of Infectious Diseases, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran b Received 13 February 2022; revised 11 April 2022; accepted 28 April 2022; Available online - - - ‫ﺍﻟﻤﻠﺨﺺ‬ ‫ ﺍﻟﻤﻼﻳﻴﻦ ﻣﻦ ﺍﻟﻨﺎﺱ ﻓﻲ ﺟﻤﻴﻊ ﺃﻧﺤﺎﺀ‬19-‫ ﺃﺻﺎﺑﺖ ﺟﺎﺋﺤﺔ ﻛﻮﻓﻴﺪ‬:‫ﺃﻫﺪﺍﻑ ﺍﻟﺒﺤﺚ‬ ‫ ﻣﻦ ﺍﻟﻤﻌﺮﻭﻑ ﺃﻥ ﺟﺮﻋﺔ‬.‫ ﺗﺮﺟﻊ ﺍﻟﻮﻓﻴﺎﺕ ﺃﺳﺎﺳﺎ ﻟﺤﺎﻟﺔ ﺍﻻﻟﺘﻬﺎﺏ ﻭﻣﻀﺎﻋﻔﺎﺗﻪ‬.‫ﺍﻟﻌﺎﻟﻢ‬ ‫ ﻗﻴﻤﺖ ﻫﺬﻩ ﺍﻟﺪﺭﺍﺳﺔ ﺟﺮﻋﺔ‬.‫ﻋﺎﻟﻴﺔ ﻣﻦ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ ﺗﻌﺘﺒﺮ ﻋﺎﻣﻼ ﻣﻀﺎﺩﺍ ﻟﻼﻟﺘﻬﺎﺑﺎﺕ‬ ‫ﻋﺎﻟﻴﺔ ﻣﻦ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ ﻛﻌﻼﺝ ﻣﺴﺎﻋﺪ ﻓﻲ ﺍﻟﺤﺎﻻﺕ ﺍﻟﺤﺮﺟﺔ ﻟﻠﻤﺮﺿﻰ ﺍﻟﻤﺼﺎﺑﻴﻦ‬ .19-‫ﺑﻌﺪﻭﻯ ﻛﻮﻓﻴﺪ‬ ‫ ﻣﻠﻎ‬21 ‫ ﺃﺟﺮﻳﻨﺎ ﺗﺠﺮﺑﺔ ﺳﺮﻳﺮﻳﺔ ﻋﺸﻮﺍﺋﻴﺔ ﻣﺰﺩﻭﺟﺔ ﺍﻟﺘﻌﻤﻴﺔ ﻟﺠﺮﻋﺔ‬:‫ﻃﺮﻕ ﺍﻟﺒﺤﺚ‬ ‫ ﺗﻢ‬.19-‫ ﻣﺮﻳﻀﺎ ﻛﻮﻓﻴﺪ‬67 ‫ﻣﻦ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ ﻓﻲ ﺍﻟﻴﻮﻡ ﻣﻘﺎﺭﻧﺔ ﻣﻊ ﺩﻭﺍﺀ ﻭﻫﻤﻲ ﺑﻴﻦ‬ ‫ ﺍﻟﻤﻮﺛﻘﺔ‬19-‫ ﻋﺎﻣﺎ ﻭﺍﻟﻤﺼﺎﺑﻴﻦ ﺑﻌﺪﻭﻯ ﻛﻮﻓﻴﺪ‬18 ‫ﺍﻟﺘﺴﺠﻴﻞ ﻟﻠﻤﺮﺿﻰ ﺍﻷﻛﺒﺮ ﻣﻦ‬ ‫ ﺍﺳﺘﻤﺮ‬.‫ﻭﺍﻟﺬﻳﻦ ﺗﻢ ﺇﺩﺧﺎﻟﻬﻢ ﺇﻟﻰ ﻭﺣﺪﺓ ﺍﻟﻌﻨﺎﻳﺔ ﺍﻟﻤﺮﻛﺰﺓ ﻭﺧﻀﻌﻮﺍ ﻟﺘﻬﻮﻳﺔ ﻣﻴﻜﺎﻧﻴﻜﻴﺔ‬ .‫ﺇﻋﻄﺎﺀ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ ﻭﺍﻟﻌﻼﺝ ﺍﻟﻮﻫﻤﻲ ﻟﻤﺪﺓ ﺧﻤﺴﺔ ﺃﻳﺎﻡ ﻣﻦ ﺧﻼﻝ ﺃﻧﺒﻮﺏ ﺃﻧﻔﻲ ﻣﻌﺪﻱ‬ ‫ ﻭﺍﻟﺘﻐﻴﺮﺍﺕ ﻓﻲ‬،‫ ﻭﻣﺪﺓ ﺍﻟﺘﻬﻮﻳﺔ ﺍﻟﻤﻴﻜﺎﻧﻴﻜﻴﺔ‬،‫ﻛﺎﻧﺖ ﺍﻟﻨﺘﺎﺋﺞ ﺍﻟﺮﺋﻴﺴﻴﺔ ﻣﻌﺪﻝ ﺍﻟﻮﻓﻴﺎﺕ‬ .‫ ﻭﻣﺴﺘﻮﻳﺎﺕ ﺍﻟﺒﺮﻭﺗﻴﻦ ﺍﻟﻤﺘﻔﺎﻋﻞ ﺳﻲ‬،‫ﻣﺆﺷﺮﺍﺕ ﺍﻷﻭﻛﺴﺠﻴﻦ‬ ‫ ﻟﻢ ﻳﻜﻦ ﻫﻨﺎﻙ ﻓﺮﻕ ﺟﻮﻫﺮﻱ ﻓﻲ ﺍﻟﻮﻓﻴﺎﺕ ﻭﻣﺪﺓ ﺍﻟﺘﻬﻮﻳﺔ ﺍﻟﻤﻴﻜﺎﻧﻴﻜﻴﺔ ﺑﻴﻦ‬:‫ﺍﻟﻨﺘﺎﺋﺞ‬ ‫ ﺍﻟﻤﺘﻮﺳﻂ ) ﺍﻻﻧﺤﺮﺍﻑ‬،‫ ﺃﻳﺎﻡ ﻣﻦ ﺍﻟﺘﺪﺧﻞ‬5 ‫ ﺑﻌﺪ‬.‫ﻣﺠﻤﻮﻋﺎﺕ ﺍﻟﺘﺤﻜﻢ ﻭﺍﻟﺘﺪﺧﻞ‬ * Corresponding address: Department of Infectious Disease, Baharloo Hospital, Tehran University of Medical Sciences, Behdari Q6 Street, Railway Square, Tehran, Iran. E-mail: h-hosami@sina.tums.ac.ir (H. Hosamirudsari) Peer review under responsibility of Taibah University. Production and hosting by Elsevier ) 47.28 ‫ﺍﻟﻤﻌﻴﺎﺭﻱ( ﻟـﻠﺒﺮﻭﺗﻴﻦ ﺍﻟﻤﺘﻔﺎﻋﻞ ﺳﻲ ﻭ ﻋﺪﺩ ﺍﻟﺼﻔﺎﺋﺢ ﺍﻟﺪﻣﻮﻳﺔ ﻛﺎﻥ‬ ‫ ﻣﻴﻜﺮﻭﻟﺘﺮ ﻓﻲ ﻣﺠﻤﻮﻋﺔ‬/  1000 (87.13 ) 195.73 ‫ ﻟﺘﺮ ﻭ‬/ ‫( ﻣﻠﻐﻢ‬38.86 /  1000 (68.03 ) 149.62 ‫ ﻟﺘﺮ ﻭ‬/ ‫( ﻣﻠﻐﻢ‬48.02 ) 75.52 ‫ﺍﻟﺘﺪﺧﻞ ﻭ‬ .‫ﻣﻴﻜﺮﻭﻟﺘﺮ ﻓﻲ ﻣﺠﻤﻮﻋﺔ ﺍﻟﺘﺤﻜﻢ ﻋﻠﻰ ﺍﻟﺘﻮﺍﻟﻲ‬ 19-‫ ﺍﺭﺗﺒﻂ ﺗﻨﺎﻭﻝ ﺟﺮﻋﺎﺕ ﻋﺎﻟﻴﺔ ﻣﻦ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ ﻓﻲ ﻣﺮﺿﻰ ﻛﻮﻓﻴﺪ‬:‫ﺍﻻﺳﺘﻨﺘﺎﺟﺎﺕ‬ ‫ ﻓﺈﻥ ﺗﺄﺛﻴﺮﻩ ﻋﻠﻰ ﻧﺘﺎﺋﺞ‬،‫ ﻭﻣﻊ ﺫﻟﻚ‬.‫ﺑﺎﻟﺘﻨﺎﻗﺺ ﻓﻰ ﻣﺴﺘﻮﻳﺎﺕ ﺍﻟﺒﺮﻭﺗﻴﻦ ﺍﻟﻤﺘﻔﺎﻋﻞ ﺳﻲ‬ .‫ﺍﻟﻤﺮﺿﻰ ﻟﻢ ﻳﻜﻦ ﻣﻠﺤﻮﻇﺎ‬ ‫؛ ﺍﻟﻤﻴﻼﺗﻮﻧﻴﻦ؛ ﺗﻨﺒﻴﺐ؛ ﻣﻌﺪﻝ ﺍﻟﻮﻓﻴﺎﺕ؛ ﺍﻟﻌﻼﺝ‬19-‫ ﻛﻮﻓﻴﺪ‬:‫ﺍﻟﻜﻠﻤﺎﺕ..
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Late treatment
is less effective
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