Razi Journal of Medical Sciences

fa بررسی تاثیر کپسول عصاره هسته Vitis vinifera در درمان بیماران کووید-۱۹: یک مطالعه دوسوکور و کنترل شده با دارونما Assessments of Vitis vinifera Seed Extract Capsules in the Treatment of COVID-19 Patients: A Double-blind Placebo-Controlled Study داروسازی Pharmacy پژوهشي Research <div style="text-align: justify;">زمینه و هدف: در حال حاضر تحقیقات برای یافتن درمان بیماری کووید-۱۹ ادامه دارد. استفاده از ترکیبات گیاهی در درمان بیماری‌ها همواره مطرح بوده است. هدف از این مطالعه بررسی تاثیر عصاره هسته انگور در درمان بیماری کووید-۱۹ می‌باشد. روش کار: تحقیق حاضر یک کارآزمایی بالینی تصادفی دوسوکور موازی بود که بر روی80  بیماران بستری مبتلا به کووید-۱۹ در بیمارستان آیت الله طالقانی آبادان در سال 1400 انجام شد. بیماران به صورت تصادفی (تصادفی بلوکی) ۲۰۰ میلی گرم عصاره هسته انگور یا دارونما دو بار در روز و به مدت 14 روز، به همراه  پروتکل ملی درمان کووید-۱۹دریافت کردند. اشباع O2، تعداد تنفس، فشار خون، شمارش کامل خون، سطح هماتوکریت، تعداد گلبول‌های سفید، سطح هموگلوبین، آلکالین فسفاتاز، نیتروژن اوره خون، سرعت رسوب گلبول‌های قرمز، آلانین آمینوترانسفراز سرم، آسپارتات آمینوترانسفراز، نسبت نرمال شده بین المللی، کراتینین سرم، زمان ترومبوپلاستین جزئی و زمان پروترومبین در ابتدا و بعد از درمان مورد بررسی و مقایسه قرار گرفتند. جهت مقایسه نتایج اولیه، آزمون تی مستقل و تحلیل رگرسیون خطرات متناسب کاکس استفاده شد. آزمون ANOVA نیز برای ارزیابی نتایج ثانویه بکارگرفته شد. برای کنترل اندازه گیری‌های پایه، آزمون ANCOVA انجام شد. یافته‌ها: هیچ یک از پارامترهای ارزیابی شده در این مطالعه بین بیماران دریافت کننده عصاره هسته انگور و گروه دارونما تفاوت معنی داری نداشت. تفاوت بین گروه مداخله و مقایسه در روزهای بستری نیم روز بود اما این تفاوت معنی دار نبود. نتیجه‌گیری: درمان با عصاره هسته انگور هیچ بهبود قابل توجهی در علائم بالینی یا یافته‌های آزمایشگاهی بیماران کووید-۱۹ ایجاد نکرد. با این حال، طبق پاور آنالیز انجام شده، عصاره هسته انگور  ممکن است در درمان کووید-۱۹ موثر باشد. در نهایت، ارزیابی این ترکیب  در جمعیت بزرگ در آینده پیشنهاد می‌شود.</div> <div style="text-align: justify;"> Background & Aims: The coronavirus disease 2019 (COVID-19) outbreak was initially announced in Wuhan, China in late December 2019, which is caused by SARS-CoV-2, and rapidly spread worldwide (1). The severity of the disease varied from asymptomatic to the need for a ventilator (3, 4). Generally, there are no beneficial antiviral drugs for COVID-19. The used medications are commonly prescribed to relieve the complications of COVID-19, such as fever, inflammation, chest pain, cough, and respiratory distress (5-7). The immune system involvement and an increase in the release of inflammatory cytokines can be observed in COVID-19 patients. On the other hand, herbal drugs with anti-inflammatory and immunomodulatory properties can be preventive and even treat COVID-19 (8). The effectiveness of natural and herbal medicines for the prevention and treatment of COVID-19 have been reported (9-11). Among herbal medicines, the grape seed extract (GSE) has valuable medicinal properties due to having proanthocyanidins, flavonoids and polyphenols compounds. GSE as a natural bioactive compound possesses several pharmacological benefits, including cardioprotective, neuroprotective, antioxidant, hepatoprotective, antidiabetic, anti-inflammatory, anticarcinogenic, antiaging, anti-cholesterol, anti-platelet and antimicrobial properties (14, 15).  Grape seed extract also exerts antiviral effects in the management of patients with human enteric virus, hepatitis A virus (HAV) (18) hepatitis C virus (HCV) (19), human immunodeficiency virus 1 (HIV) (20), and human norovirus surrogates, such as murine norovirus (MNV-19) (21) and feline calicivirus (FCV) strain F9. But its effects on COVID-19 remain unclear. The purpose of this study was to evaluate the effects of GSE on the treatment of hospitalized patients with COVID-19. Methods: The current double-blind, parallel, randomized clinical trial was performed in 2021 on Ayatollah Taleghani Hospital, Abadan, Iran. The supplemental Figure 1 presents the study flowchart. COVID-19 cases (N=80) were randomly assigned to the GSE and placebo groups via block randomization using block randomization (block sizes of 4 and 8, respectively). The GSE group was given one capsule of GSE (with 200 mg of GSE) every 12 hours, plus national standard treatment for COVID-19. The placebo group was treated with placebo capsules. The COVID-19 clinical symptoms, respiratory rate, O2 saturation (SaO2), and blood pressure were evaluated at baseline and on day 14. Complete blood count, hematocrit level, white blood cell count, hemoglobin level, alkaline phosphatase, blood urea  nitrogen, erythrocyte sedimentation rate, serum alanine aminotransferase, aspartate aminotransferase, international normalized ratio, serum creatinine, partial thromboplastin time, and prothrombin time were evaluated at baseline and after the treatment. Comparison of the primary outcome of this study (hospital stay difference) was done between the two groups by independent t-test and Cox proportional hazards regression analysis. ANOVA test was also used to evaluate secondary outcomes. To control for the baseline measurements, ANCOVA test was performed. Results: The patients’ baseline information in the placebo and GSE groups is shown in Table 1. Moreover, an intention-to-treat analysis was our primary analysis on all patients with random assignment. Based on t-test, the hospital stay was half a day longer in the placebo group than the GSE group; however, this difference was not significant (mean difference=0.5; 95% CI: -1.09-2.09; P=0.53). The secondary outcomes were compared using t-test (Table 2). Based on the results of this table, no significant difference was found between the secondary outcomes, except for the red blood cells (RBC) and hemoglobin level. After adjusting for the baseline values of RBC and hemoglobin based on the analysis of covariance (ANCOVA), no significant difference was detected between the two groups in these two variables (mean difference for RBC= -0.11; 95% CI: -0.32, 0.08; P=0.26; mean difference for Hb= -1.78, 95% CI: -3.64, -0.08, P=0.06). After expanding the data to the sample size using an expansion module in STATA (version 12), a 17% difference in the mean duration of hospitalization became significant between the GSE and placebo groups (HR=0.85; 95% CI: 0.93-0.33; P=0.001). After controlling for age, sex, and blood pressure, this relationship remained significant. Conclusion: The results indicated that GSE did not affect the clinical signs or biochemical markers of 80 patients evaluated in this study. However, the power analysis showed that the difference in hospital stay would be significant if the study was performed on a larger sample size (about 1,273 cases) in each group. Due to similarities between HCV, HIV and SARS-CoV-2, medicines that are used for the treatment of HIV and HCV have been also suggested for COVID-19. One of the similarities between HIV and COVID-19 is that both viruses can increase the generation of proinflammatory cytokines. They increase the formation of cytokines involved in secondary complications associated with the viral load of SARS-CoV-2 (29). Since no specific accepted antiviral medicine is available to treat COVID-19, antiviral agents for HIV and HCV infections have been suggested for treatment (29, 30). Evidence suggests that GSE has antiviral effects against human enteric virus, hepatitis A virus (18), HCV(19) , HIV-1 (20), and human norovirus surrogates, including the MNV-19 and FCV (21) .It is known that GSE contains a high level of proanthocyanidins, can suppress HCV replication (34). Zannella et al 2021, indicated that Vitis vinefra leaf extract showed the inhibitory effect on SARS-CoV-2 replication in the early stages of infection. They suggested that directly blocking the proteins enriched on the viral surface may be involved mechanism (22). According findings of Hajibeygi et al in 2022, diet Iranian traditional including Ficus carica; Vitis vinifera; Cicer arietinum; Descurainiasophia seeds, Safflower, Ziziphus jujuba, chicken soup; barley soup, rose water, and saffron and cinnamon spices decrease the inflammatory markers and CPR level in COVID-10 patients (23). So, recent studies indicated the efficacy of different parts of Vitis vinifera in decreasing symptoms of COVID-19, but more researches with a larger sample size was suggested. GSE did not have significant effects on the biochemical markers and signs of COVID-19. However, the current study is the first randomized controlled trial, in which the GSE effects were observed in COVID-19 patients. This clinical trial had some limitations. Such as it was conducted in the main referral hospital for COVID-19 patients with low population, severity of disease was not considered and total extract of Grape seed was used. Finally, it is suggested to conduct a similar survey as a multi-center trial on a large population in the future.</div> عصاره هسته انگور, کووید-19, گیاهان دارویی , درمان دارویی کووید-19 Vitis vinifera, Grape seed extract, COVID-19, Herbal, COVID-19 Drug Treatment 1 13 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7486-1&slc_lang=fa&sid=1 Hoda Mojiri_Forushani هدا مجیری فروشانی dr.mojiri@yahoo.com 3900319475328460089881 3900319475328460089881 Yes Assistant Professor, Clinical Research Development Unit, Taleghani Educational Hospital, Abadan University of Medical Sciences, Abadan, Iran استادیار فارماکولوژی، مرکز تحقیقات بالینی مرکز آموزشی آیت الله طالقانی، دانشگاه علوم پزشکی آبادان، آبادان، ایران Aliasghar Hemmati علی اصغر همتی 3900319475328460089882 3900319475328460089882 No Professor, Marine Pharmaceutical Research Center, School of Pharmacy, Ahvaz Judishapur University of Medical Sciences, Ahvaz, Iran استاد فارماکولوژی، مرکز تحقیقات علوم دریایی، دانشکده داروسازی، دانشگاه علوم پزشکی جندی شاپور اهواز، اهواز، ایران Saeid Bitaraf سعید بیطرف 3900319475328460089883 3900319475328460089883 No Epidemiologist, Clinical Sciences Research Institute, Judishapur University of Medical Sciences, Ahvaz, Iran اپیدمیولوژیست، موسسه تحقیقات علوم بالینی، دانشگاه علوم پزشکی چندی شاپور، اهواز، ایران Mona Ebrahimzadeh منا ابراهیم زاده 3900319475328460089884 3900319475328460089884 No Instructor, Clinical Research Development Unit, Taleghani Educational Hospital, Abadan University of Medical Sciences, Abadan, Iran مربی پرستاری، مرکز تحقیقات بالینی مرکز آموزشی آیت الله طالقانی، دانشگاه علوم پزشکی آبادان، آبادان، ایران Elham Matouri الهام مطوری 3900319475328460089885 0009-0001-5659-5053 No Nursing Student, Clinical Research Development Unit, Taleghani Educational Hospital, Abadan University of Medical Sciences, Abadan, Iran دانشجوی پرستاری، مرکز تحقیقات بالینی مرکز آموزشی آیت الله طالقانی، دانشگاه علوم پزشکی آبادان، آبادان، ایران Eilnaz Ghanavati ایلناز قنواتی 3900319475328460089886 0009-0008-6554-3715 No Nursing Student, Clinical Research Development Unit, Taleghani Educational Hospital, Abadan University of Medical Sciences, Abadan, Iran دانشجوی پرستاری، مرکز تحقیقات بالینی مرکز آموزشی آیت الله طالقانی، دانشگاه علوم پزشکی آبادان، آبادان، ایران Alireza Eisvand Mahmudi علیرضا عیسوند محمودی 3900319475328460089887 0009-0004-5348-6283 No Nursing Student, Clinical Research Development Unit, Taleghani Educational Hospital, Abadan University of Medical Sciences, Abadan, Iran دانشجوی پرستاری، مرکز تحقیقات بالینی مرکز آموزشی آیت الله طالقانی، دانشگاه علوم پزشکی آبادان، آبادان، ایران