Phase II, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial Investigating the Efficacy of Mebendazole in the Management of Symptomatic COVID-19 Patients

被引:3
作者
El-Tanani, Mohamed [1 ,2 ]
Ahmed, Khaled Abdul-Aziz [1 ,3 ]
Shakya, Ashok K. [1 ]
Ammari, Wesam G. [1 ]
Al-Shudifat, Abdel-Elah [4 ]
机构
[1] Al Ahliyya Amman Univ, Pharmacol & Diagnost Res Ctr PDRC, Amman 19328, Jordan
[2] Univ Bradford, Inst Canc Therapeut, Fac Life Sci, Bradford BD7 1DP, England
[3] Al Ahliyya Amman Univ, Fac Allied Med Sci, Dept Med Lab Sci, Amman 19328, Jordan
[4] Hashemite Univ, Fac Med, Dept Internal & Family Med, Zarqa 13133, Jordan
关键词
placebo-controlled clinical trial; mebendazole; COVID-19; outpatients; repurposing; ANTIVIRAL ACTIVITY; IVERMECTIN; ALVEOLAR; CANDIDATE; DRUGS;
D O I
10.3390/ph16060799
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The outbreak of the COVID-19 pandemic has spread throughout the world, affecting almost all nations and territories. The current double-blind, randomized, placebo-controlled, phase II clinical trial sought to evaluate the clinical efficacy and safety of mebendazole as an adjuvant therapy for outpatients with COVID-19. The patients were recruited and divided into two groups: a Mebendazole-treated group and placebo group. The mebendazole and placebo groups were matched for age, sex, and complete blood count (CBC) with differential and liver and kidney function tests at baseline. On the third day, the C-reactive protein (CRP) levels were lower (2.03 & PLUSMN; 1.45 vs. 5.45 & PLUSMN; 3.95, p < 0.001) and the cycle threshold (CT) levels were higher (27.21 & PLUSMN; 3.81 vs. 24.40 & PLUSMN; 3.09, p = 0.046) significantly in the mebendazole group than in the placebo group on the third day. Furthermore, CRP decreased and CT dramatically increased on day three compared to the baseline day in the mebendazole group (p < 0.001 and p = 0.008, respectively). There was a significant inverse correlation between lymphocytes and CT levels in the mebendazole group (r = -0.491, p = 0.039) but not in the placebo group (r = 0.051, p = 0.888). Mebendazole therapy increased innate immunity and returned inflammation to normal levels in COVID-19 outpatients faster than it did in the placebo group in this clinical trial. Our findings add to the growing body of research on the clinical and microbiological benefits of repurposing antiparasitic therapy, specifically mebendazole, for SARS-CoV-2 infection and other viral infections.
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页数:12
相关论文
共 58 条
[1]   FDA approved drugs with antiviral activity against SARS-CoV-2: From structure-based repurposing to host-specific mechanisms [J].
Ahmed, Mahmoud S. ;
Farag, Ayman B. ;
Boys, Ian N. ;
Wang, Ping ;
Menendez-Montes, Ivan ;
Nguyen, Ngoc Uyen Nhi ;
Eitson, Jennifer L. ;
Ohlson, Maikke B. ;
Fan, Wenchun ;
McDougal, Matthew B. ;
Mar, Katrina ;
Thet, Suwannee ;
Ortiz, Francisco ;
Kim, Soo Young ;
Solmonson, Ashley ;
Williams, Noelle S. ;
Lemoff, Andrew ;
DeBerardinis, Ralph J. ;
Schoggins, John W. ;
Sadek, Hesham A. .
BIOMEDICINE & PHARMACOTHERAPY, 2023, 162
[2]  
Al-Balas Mahmoud, 2021, Open Respir Med J, V15, P28, DOI [10.2174/1874306402115010028, 10.2174/1874306402115010028]
[3]   Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis [J].
Alamer, Ahmad ;
Alrashed, Ahmed A. ;
Alfaifi, Mashael ;
Alosaimi, Bandar ;
AlHassar, Fatimah ;
Almutairi, Malak ;
Howaidi, Jude ;
Almutairi, Wedad ;
Mohzari, Yahya ;
Sulaiman, Tarek ;
Al-jedai, Ahmed ;
Alajami, Hamdan N. ;
Alkharji, Fatima ;
Alsaeed, Ali ;
Alali, Alaa H. ;
Baredhwan, Abdullah A. ;
Abraham, Ivo ;
Almulhim, Abdulaziz S. .
CURRENT MEDICAL RESEARCH AND OPINION, 2021, 37 (07) :1085-1097
[4]   Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway [J].
Andersson, Claes R. ;
Selvin, Tove ;
Blom, Kristin ;
Rubin, Jenny ;
Berglund, Malin ;
Jarvius, Malin ;
Lenhammar, Lena ;
Parrow, Vendela ;
Loskog, Angelica ;
Fryknas, Marten ;
Nygren, Peter ;
Larsson, Rolf .
SCIENTIFIC REPORTS, 2020, 10 (01)
[5]  
[Anonymous], Worldometer COVID-19 Coronavirus Pandemic: Portugal
[6]  
[Anonymous], 2012, LiverTox: Clinical and Research Information on Drug-Induced Liver Injury
[7]  
Ayaz M.M., 2021, Coronavirus disease 2019 (COVID-19) treatment guidelines, V2, P52, DOI 10.2174/9781681089072121020006
[8]   Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition [J].
Blom, Kristin ;
Rubin, Jenny ;
Berglund, Malin ;
Jarvius, Malin ;
Lenhammar, Lena ;
Parrow, Vendela ;
Andersson, Claes ;
Loskog, Angelica ;
Fryknas, Marten ;
Nygren, Peter ;
Larsson, Rolf .
BMC RESEARCH NOTES, 2019, 12 (1)
[9]   Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial [J].
Bosaeed, Mohammad ;
Alharbi, Ahmad ;
Mahmoud, Ebrahim ;
Alrehily, Sanaa ;
Bahlaq, Mohannad ;
Gaifer, Zied ;
Alturkistani, Hanan ;
Alhagan, Khaled ;
Alshahrani, Saad ;
Tolbah, Ali ;
Musattat, Abrar ;
Alanazi, Maha ;
Jaha, Raniah ;
Sultana, Khizra ;
Alqahtani, Hajar ;
Al Aamer, Kholoud ;
Jaser, Saud ;
Alsaedy, Abdulrahman ;
Ahmad, Ayoub ;
Abalkhail, Mohammed ;
AlJohani, Sameera ;
Al Jeraisy, Majed ;
Almaziad, Sultan ;
Albaalharith, Nahlah ;
Alabdulkareem, Khaled ;
Alshowair, Abdulmajeed ;
Alharbi, Naif Khalaf ;
Alrabiah, Fahad ;
Alshamrani, Majid ;
Aldibasi, Omar ;
Alaskar, Ahmed .
CLINICAL MICROBIOLOGY AND INFECTION, 2022, 28 (04) :602-608
[10]   Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19 [J].
Bosaeed, Mohammad ;
Alharbi, Ahmad ;
Hussein, Mohammad ;
Abalkhail, Mohammed ;
Sultana, Khizra ;
Musattat, Abrar ;
Alqahtani, Hajar ;
Alshamrani, Majid ;
Mahmoud, Ebrahim ;
Alothman, Adel ;
Alsaedy, Abdulrahman ;
Aldibasi, Omar ;
Alhagan, Khalid ;
Asiri, Abdullah Mohammed ;
AlJohani, Sameera ;
Al-Jeraisy, Majed ;
Alaskar, Ahmed .
BMJ OPEN, 2021, 11 (04)