Comparison of micafungin and voriconazole as empirical antifungal therapies in febrile neutropenic patients with hematological disorders: a randomized controlled trial
Abstract:The clinical efficacy did not differ between micafungin and voriconazole. Micafungin was generally better tolerated than voriconazole when given as an empirical antifungal therapy in patients with persistent fever and neutropenia.
“…4 studies employed the appropriate random sequence generation and allocation concealment [8, 9, 14, 32], while others were unclear due to their failure to state the detailed randomization and allocation method [10, 29, 30]. Authors of 2 RCTs reported that they employed blinded assessors [14, 29] while others were open-label or unclear trials.…”
BackgroundCurrent studies that compare the efficacy and safety of micafungin (MCFG) with that of triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) demonstrate a lack of sufficient evidence and yield conflicting results. To compare the efficacy and safety of MCFG and triazoles in the prevention and treatment of IFIs, we conducted a meta-analysis and trial sequential analysis (TSA).MethodsFor the meta-analysis, we systematically searched the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials and relevant database articles for randomized controlled studies published through November 2016. Comparative studies of the efficacy and safety of MCFG versus triazoles in the prevention and treatment of IFIs were selected. Meta-analysis was performed by R software with the “metafor” package. Pooled results were expressed as risk ratios (RRs) with corresponding 95% confidence intervals (CI). TSA was adopted to assess the studies’ power with TSA version 0.9 beta.ResultsNine current studies were included in the meta-analysis (1049 cases and 959 controls). Pooled trial comparisons indicated that MCFG does have significantly higher treatment success rates (RR = 1.13; 95% CI, 1.02–1.25; p = 0.0205) and reduces the number of overall IFIs (RR = 0.75; 95% CI, 0.61–0.92; p = 0.0056). However, MCFG demonstrates no difference in all-cause mortality (RR = 0.76; 95% CI, 0.52–1.12, p = 0.1624). For the safety evaluation, MCFG had a significantly lower incidence of severe adverse events (AEs) (RR = 0.45; 95% CI, 0.25–0.83; p = 0.0105), hepatic impairment (RR = 0.70; 95% CI, 0.50–0.97; p = 0.0363) and premature discontinuation (RR = 0.51; 95% CI, 0.34–0.76, p = 0.0010). Meta-regression analysis disclosed the correction of mean age and treatment success rates (P < 0.0001). Meanwhile, TSA demonstrated sufficient power to show efficacy.ConclusionsThe treatment success rate of MCFG is superior to that of triazoles for the prophylaxis and treatment of IFIs, and correction of the mean patient age demonstrates that efficacy increases as patient age decreases. MCFG appears to be well-tolerated with manageable side effects and lower withdrawal rates. However, additional clinical trials should be conducted on specific drug-related mortality and AEs to gather sufficient evidence on these matters.
“…4 studies employed the appropriate random sequence generation and allocation concealment [8, 9, 14, 32], while others were unclear due to their failure to state the detailed randomization and allocation method [10, 29, 30]. Authors of 2 RCTs reported that they employed blinded assessors [14, 29] while others were open-label or unclear trials.…”
BackgroundCurrent studies that compare the efficacy and safety of micafungin (MCFG) with that of triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) demonstrate a lack of sufficient evidence and yield conflicting results. To compare the efficacy and safety of MCFG and triazoles in the prevention and treatment of IFIs, we conducted a meta-analysis and trial sequential analysis (TSA).MethodsFor the meta-analysis, we systematically searched the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials and relevant database articles for randomized controlled studies published through November 2016. Comparative studies of the efficacy and safety of MCFG versus triazoles in the prevention and treatment of IFIs were selected. Meta-analysis was performed by R software with the “metafor” package. Pooled results were expressed as risk ratios (RRs) with corresponding 95% confidence intervals (CI). TSA was adopted to assess the studies’ power with TSA version 0.9 beta.ResultsNine current studies were included in the meta-analysis (1049 cases and 959 controls). Pooled trial comparisons indicated that MCFG does have significantly higher treatment success rates (RR = 1.13; 95% CI, 1.02–1.25; p = 0.0205) and reduces the number of overall IFIs (RR = 0.75; 95% CI, 0.61–0.92; p = 0.0056). However, MCFG demonstrates no difference in all-cause mortality (RR = 0.76; 95% CI, 0.52–1.12, p = 0.1624). For the safety evaluation, MCFG had a significantly lower incidence of severe adverse events (AEs) (RR = 0.45; 95% CI, 0.25–0.83; p = 0.0105), hepatic impairment (RR = 0.70; 95% CI, 0.50–0.97; p = 0.0363) and premature discontinuation (RR = 0.51; 95% CI, 0.34–0.76, p = 0.0010). Meta-regression analysis disclosed the correction of mean age and treatment success rates (P < 0.0001). Meanwhile, TSA demonstrated sufficient power to show efficacy.ConclusionsThe treatment success rate of MCFG is superior to that of triazoles for the prophylaxis and treatment of IFIs, and correction of the mean patient age demonstrates that efficacy increases as patient age decreases. MCFG appears to be well-tolerated with manageable side effects and lower withdrawal rates. However, additional clinical trials should be conducted on specific drug-related mortality and AEs to gather sufficient evidence on these matters.
“…The ideal prophylactic antifungal therapy should be safe and well tolerated for long-term use, being effective against a wide spectrum of organisms and available as intravenous and oral formulations with good bioavailability (17). Recent randomized controlled trials (RCTs) (18)(19)(20)(21) and meta-analyses (22)(23)(24) showed a marked reduction of IFIs in patients who used triazoles and echinocandins. The currently available multiple polyenes, echinocandins, and triazoles fulfill some of the requirements for an ideal prophylactic antifungal agent; however, some areas for improvement remain.…”
Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments. We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). We searched Embase, PubMed, the Cochrane Central Register of Controlled Clinical Trials, and the www.ClinicalTrials.gov website. In total, 54 RCTs were identified, including 13 treatment options. The evidence was synthesized using a network meta-analysis. Relative risk (RR) was adopted. Posaconazole was ranked highest in effectiveness for primary prophylaxis, being the most favorable in terms of (i) the RR for reduction of invasive fungal infection (0.19; 95% confidence interval [CI], 0.11 to 0.36) and (ii) the probability of being the best option (94% of the cumulative ranking). Posaconazole also demonstrated its efficacy in preventing invasive aspergillosis and proven fungal infections, with RR of 0.13 (CI, 0.03 to 0.65) and 0.14 (CI, 0.05 to 0.38), respectively. However, there was no significant difference among all of the antifungal agents in all-cause mortality and overall adverse events. Our network meta-analysis provided an integrated overview of the relative efficacy of all available treatment options for primary fungal prophylaxis for neutropenic fever in hematological malignancy patients under myelosuppressive chemotherapy or hematopoietic cell transplantation. On the basis of this analysis, posaconazole seems to be the most effective prophylaxis option until additional data from head-to-head randomized controlled trials become available.
“…Figure 2 presents the results of the systematic bias analysis. There was a low risk of bias for most items, except for the presence of performance and detection bias due to the lack of a double-blind design and blind outcome assessment in four studies [ 18 , 22 , 27 , 32 ]. Fig.…”
BackgroundVoriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption. The aim of this study was to comprehensively compare voriconazole-induced toxicity, including tolerability, neurotoxicity, visual toxicity, hepatotoxicity and nephrotoxicity with the composite of other antifungals commonly used in clinic.MethodsBibliography databases were searched to select randomized controlled trials providing information about the incidence of toxicity referred above. A total of 4122 patients from 16 studies were included in the meta-analysis.ResultsAnalysis of individual types of toxicity showed that there was a significant difference between voriconazole and the composite of other antifungal agents. The primary outcome, the tolerability of voriconazole was slightly inferior (OR = 1.71, 95% CI = 1.21–2.40, P = 0.002) and it is noteworthy that the probabilities of neurotoxicity and visual toxicity were around twice higher and six-fold for voriconazole compared with the counterpart (OR = 1.99, 95% CI = 1.05–3.75, P = 0.03 and OR = 6.50, 95% CI = 2.93–14.41, P < 0.00001, respectively). Hepatotoxicity was more common in voriconazole group (OR = 1.60, 95% CI = 1.17–2.19, P = 0.003) whereas its pooled risk of nephrotoxicity was about half of the composite of other five antifungal agents (OR = 0.46, 95% CI = 0.26–0.84, P = 0.01).ConclusionOur analysis has revealed differences in multiple types of toxicity induced by VRC versus other antifungals and quantified the corresponding pooled risks, which could provide an alternative for patients with a certain antifungal intolerance and help the clinician to select the optimal intervention.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2913-8) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
