First-Line Systemic Treatment Strategies for Unresectable Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

ObjectiveSeveral new first-line treatments were recently approved for unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compare the efficacy and safety of first-line systemic treatments to provide information for clinical decision making in unresectable HCC.MethodsPubmed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, Embase, Google Scholar, the Cochrane Library, EMbase, CNKI, CBM, VIP, and the Wanfang databases, as well as the Cochrane Central Register of Controlled Trails were searched for randomized clinical trials evaluating the efficacy of first-line chemotherapy, molecular targeted therapy, or immunotherapy for unresectable HCC. Hazard ratios with 95% confidence intervals (CIs) were calculated to explore the effects of various treatment options on overall survival (OS) and progression-free survival (PFS), whereas odd ratios with 95% CIs were used for adverse events (AEs) and serious adverse events (SAEs). A network meta-analysis was performed to synthesize data and for direct and indirect comparisons between treatments. The cumulative ranking curve (SUCRA) and P score were used to rank treatments. The risk of bias across studies was assessed graphically and numerically using the funnel plot and Egger’s regression test.ResultsFifteen studies including 9005 patients were analyzed. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, and donafenib had better OS outcomes than sorafenib. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, lenvatinib, and linifanib had better PFS outcomes than sorafenib. The results of network meta-analysis showed that sintilimab plus bevacizumab was associated with the best OS and PFS. Egger’s tests indicated that none of the included studies had obvious publication deviation.ConclusionSintilimab plus bevacizumab showed the best OS and PFS outcomes with no additional AEs or SAEs. Thus, sintilimab plus bevacizumab may be a better first line choice for the treatment of patients with unresectable HCC.Systematic Review RegistrationPROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD42021269734.

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Abiraterone acetate (AA) or docetaxel (D) in metastatic castration-sensitive prostate cancer (mCSPC): A systematic review and network meta-analysis of randomized clinical trials (RCTs).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.243 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 243-243

Author(s):

Irbaz Bin Riaz ◽

Abdulaali Almutairi ◽

Zeeshan Ali ◽

Abdullah Alhifany ◽

Sandipan Bhattacharjee ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Statistical Significance ◽

Random Effect ◽

Indirect Comparison ◽

Cochrane Library ◽

Cochrane Central Register

243 Background: AA and D have been shown in separate trials to increase overall survival in patients with mCSPC compared to Androgen Derivation Therapy (ADT). In the absence of head to head clinical trials and to provide clinical guidance, we performed an indirect comparison of AA and D using network meta-analysis. Methods: We performed a search of MEDLINE, EMBASE, Cochrane Library, and Cochrane Central Register of Controlled Trials to identify relevant clinical trials. Collected data included hazard ratio and confidence interval (CI) for Overall Survival (OS) and number of adverse events in each study arm. Risk for bias was assessed using the Cochrane Collaboration’s tool. Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 software (MRC Biostatistics Unit, Cambridge, UK) to perform an indirect comparison of D and AA. Results: Five clinical trials were included in this analysis. Two trials (LATITUDE, STAMPEDE) compared AA to ADT and three trials (CHAARTED,STAMPEDE, GETUG-AFU 15 study) compared D to ADT. Results from both fixed effect and random effect network meta-analyses for the primary outcome (OS) revealed no statistical significance between AA and D (HR 0.81,95%CI 0.65-1.01; HR 0.81, 95%CI 0.40-1.82) respectively. Comparatively, abiraterone had statistically significant fewer events of anemia (OR 0.14,95%CI 0.08-0.23), neutropenia (OR 0.06,95%CI 0.03-0.12), peripheral edema (OR 0.21,95%CI 0.09-0.44), dyspnea (OR 0.22,95%CI 0.08-0.51), nausea (OR 0.09,95%CI 0.02-0.24), diarrhea (OR 0.06,95%CI 0.02-0.15), constipation (OR 0.25,95%CI 0.11-0.53), and fatigue (OR 0.12,95%CI 0.07-0.20). AA had statistically significant more events of hot flashes (OR 3.85, 95% CI2.33-6.25). For other adverse events, both drugs were statistically similar. Conclusions: There is no difference in OS using AA for longer periods in CSPC than a regimen of a limited number of cycles of D. There are significant differences in side effect profile of these drugs. Further analyses are needed to determine cost effectiveness of AA vs D under consideration of comparative efficacy and safety.

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675 FUNDOPLICATION VERSUS ORAL PROTON PUMP INHIBITORS FOR GASTROESOPHAGEAL REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Diseases of the Esophagus ◽

10.1093/dote/doab052.675 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Luca Schiliró Tristão ◽

Francisco Tustumi ◽

Guilherme Tavares ◽

Letícia Nogueira Datrino ◽

Maria Carolina Andrade Serafim ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Adverse Events ◽

Proton Pump ◽

Reflux Disease ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Oral Intake

Abstract Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few is reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies. Methods This systematic review was guided by PRISMA statement. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. The inclusion criteria were (I) patients with GERD; (II) Randomized clinical trials, comparing oral intake PPI with FPT; (III) relevant outcomes for this review. The exclusion criteria were (I) reviews, case reports, editorials and letters (II) transoral or endoscopic FPT (III) studies with no full text. No restrictions were set for language or period. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool. Results Ten RCT were included. Meta-analysis showed that heartburn (RD = −0.19; 95% CI = −0.29, −0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). There was no significant difference between groups in the percentage of time with pH less than 4 in 24 hours, sustained remission and Gastrointestinal Symptom Rating Scale. Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching. Conclusion FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT, such as those with severe erosive esophagitis, severe respiratory symptoms, low adherence to continuous drug treatment and patients with non-acid reflux, to ensure better results.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Systematic Review of Randomized Clinical Trials of Acupressure Therapy for Primary Dysmenorrhea

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/169692 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Hui-ru Jiang ◽

Shuang Ni ◽

Jin-long Li ◽

Miao-miao Liu ◽

Ji Li ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Statistical Analysis ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Controlled Trials ◽

Cochrane Central Register ◽

Primary Dysmenorrhea ◽

Randomized Controlled ◽

Central Register

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (−1.41 cm 95% CI [−1.61, −1.21]), SF-MPQ at the 3-month followup (WMD −2.33, 95% CI [−4.11, −0.54]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]), and MDQ at the 3-month followup (WMD −2.31, 95% CI [−3.74, −0.87]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials.

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Systematic Review and Meta-Analysis of Randomized Clinical Trials on Chemomechanical Caries Removal

Operative Dentistry ◽

10.2341/14-021-lit ◽

2015 ◽

Vol 40 (4) ◽

pp. E167-E178 ◽

Cited By ~ 14

Author(s):

HHH Hamama ◽

CKY Yiu ◽

MF Burrow ◽

NM King

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Sodium Hypochlorite ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Assessment Process ◽

Cochrane Library ◽

Removal Method ◽

Caries Removal ◽

Caries Excavation

SUMMARY Objectives The aim of this review was to assess the methodologies used in previously published prospective randomized clinical trials on chemomechanical caries removal and to conduct a meta-analysis to quantify the differences in the excavation time between chemomechanical and conventional caries removal methods. Methods An electronic search was performed using Scopus, PubMed, EBSCO host, and Cochrane Library databases. The following categories were excluded during the assessment process: non-English studies published before 2000, animal studies, review articles, laboratory studies, case reports, and nonrandomized or retrospective clinical trials. The methodologies of the selected clinical trials were assessed. Furthermore, the reviewed clinical trials were subjected to meta-analysis for quantifying the differences in excavation time between the chemomechanical and the conventional caries removal techniques. Results Only 19 randomized clinical trials fit the inclusion criteria of this systematic review. None of the 19 reviewed trials completely fulfilled Delphi's ideal criteria for quality assessment of randomized clinical trials. The meta-analysis results revealed that the shortest mean excavation time was recorded for rotary caries excavation (2.99±0.001 minutes), followed by the enzyme-based chemomechanical caries removal method (6.36±0.08 minutes) and the the hand excavation method (atraumatic restorative technique; 6.98±0.17 minutes). The longest caries excavation time was recorded for the sodium hypochlorite-based chemomechanical caries removal method (8.12±0.02 minutes). Conclusions It was found that none of the current reviewed trials fulfilled all the ideal requirements of clinical trials. Furthermore, the current scientific evidence shows that the sodium hypochlorite-based (Carisolv) chemomechanical caries removal method was more time consuming when compared to the enzyme-based (Papacarie) chemomechanical and the conventional caries removal methods. Further prospective randomized controlled clinical trials evaluating the long-term follow-up of papain-treated permanent teeth are needed.

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Acupuncture in oncological pain relief: A systematic review of randomized clinical trials

Fisioterapia em Movimento ◽

10.1590/fm.2021.34203 ◽

2021 ◽

Vol 34 ◽

Author(s):

Michel Marcos Dalmedico ◽

Caroline Machado de Toledo ◽

Paula Karina Hembecker ◽

Juliana Londero Silva Ávila ◽

Chayane Karla Lucena de Carvalho ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Cancer Pain ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cochrane Central Register ◽

Opioid Use ◽

Central Register ◽

Considerable Impact ◽

Analgesic Use

Abstract Introduction: Cancer pain has a considerable impact on patients’ health and quality of life, and its treatment is essentially based on opioid use. Objective: To report the effectiveness of acupuncture in relieving cancer pain (secondary to the disease or to the corresponding therapy) or in decreasing opioid use compared to other interventions. Methods: A systematic review of randomized clinical trials was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The trials were selected from the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: The search strategy resulted in the inclusion of eight trials, of which five compared acupuncture and drug therapy and three compared acupuncture and placebo. Seven trials reported decreased pain and analgesic use. The trials showed clinical heterogeneity, making a meta-analysis unfeasible. Conclusion: The findings herein provided no robust evidence to support the routine use of acupuncture as an adjuvant therapy in the treatment of cancer pain. However, its use is promising since the results showed a trend toward decreased pain and analgesic use, thus justifying further studies in the future.

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Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

10.1101/2020.09.30.20204693 ◽

2020 ◽

Author(s):

Joseph A. Ladapo ◽

John E. McKinnon ◽

Peter A. McCullough ◽

Harvey Risch

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Side Effects ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Randomized Controlled ◽

Exposure Prophylaxis

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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The effects of garlic supplementation on weight loss: A systematic review and meta-analysis of randomized controlled trials

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000607 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Manije Darooghegi Mofrad ◽

Jamal Rahmani ◽

Hamed Kord Varkaneh ◽

Alireza Teymouri ◽

Seyed Mohammad Mousavi

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Body Weight ◽

Waist Circumference ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Pooled Analysis ◽

Cochrane Library ◽

Random Effects Models ◽

Online Databases

Abstract. Obesity is related to increase in the incidence of morbidity and mortality. Studies have suggested anti-obesity properties of garlic; however, results are inconsistent. This systematic review and meta-analysis is done to summarize the data obtained from available randomized clinical trials on the effect of garlic supplementation on body weight, Body Mass Index (BMI), and Waist Circumference (WC). The online databases of Scopus, PubMed, Google Scholar and Cochrane library were searched until March 2018 for related publications using relevant keywords. Effect sizes of eligible studies were pooled using random-effects models. Cochran’s Q-test and I2 index were used for assessing heterogeneity. We found 1241 records in our initial search, of which 13 randomized clinical trials (RCTs) with 15 treatment arms were included. Pooled analysis showed that garlic administration might significantly decrease WC (Weighed Mean Difference (WMD): −1.10 cm, 95% CI: −2.13, −0.07, P = 0.03, I2 = 0%). However, garlic intervention had no significant effect on body weight (WMD): −0.17 kg, 95% CI: −0.75 to 0.39, P = 0.54, I2 = 0%) and BMI (WMD: −0.17 kg/m2, 95% CI: −0.52, 0.16, P = 0.30, I2 = 44.5%) as compared to controls. From Subgroup analysis, it was ascertained that the effect of garlic supplementation on BMI was significant in trials with duration < 12 weeks (WMD: −0.58 kg/m2, 95% CI: −1.08, −0.08, I2 = 19.8%, P = 0.02) compared to those with higher duration (>12 weeks). The current meta-analysis results suggest that garlic supplementation seems to reduce waist circumference unlike body weight and BMI.

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The Effects of Resveratrol on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666191116112950 ◽

2020 ◽

Vol 20 (5) ◽

pp. 718-727 ◽

Cited By ~ 2

Author(s):

Mahsa Omidian ◽

Mina Abdolahi ◽

Elnaz Daneshzad ◽

Mohsen Sedighiyan ◽

Mohadeseh Aghasi ◽

...

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Serum Levels ◽

Oxidative Stress Marker ◽

Cochrane Library ◽

Oxidative Stress Markers ◽

Stress Markers

Objective: Recent trial studies have found that resveratrol supplementation beneficially reduces oxidative stress marker, but, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of resveratrol supplementation on oxidative stress parameters. Methods: We searched databases of Pubmed, Scopus and Cochrane Library up to December 2018 with no language restriction. Studies were reviewed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane handbook. To compare the effects of resveratrol with placebo, weighted mean difference (WMD) with 95% confidence intervals (CI) were pooled based on the random-effects model. Results: Among sixteen clinical trials, we found that resveratrol supplementation increased GPx serum levels significantly (WMD: 18.61; 95% CI: 8.70 to 28.52; P<0.001) but had no significant effect on SOD concentrations (WMD: 1.01; 95% CI: -0.72 to 2.74; P= 0.25), MDA serum levels (WMD: -1.43; 95% CI: -3.46 to 0.61; P = 0.17) and TAC (WMD: -0.09; 95% CI: -0.29 to 0.11; P = 0.36) compared to placebo. Finally, we observed that resveratrol supplementation may not have a clinically significant effect on oxidative stress. Conclusion: However, the number of human trials is limited in this context, and further large prospective clinical trials are needed to confirm the effect of resveratrol supplement on oxidative stress markers.

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