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Efficacy of Lianhuaqingwen Capsule Compared With Oseltamivir for Influenza A Virus Infection: A Meta-analysis of Randomized, Controlled Trials
Pan Zhao, MD, PhD; Hao-zhen Yang; Hong-yu Lv; Zhen-man Wei
ABSTRACT In this meta-analysis, the authors review the results of studies on the efficacy of lianhuaqingwen capsule (LHQW-C) compared with oseltamivir in treating influenza A virus infection. The authors searched PubMed, Embase, Wanfang Data, and the China National Knowledge Infrastructure (CNKI) from the date of inception until December 31, 2012. The Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were also searched. Five randomized, controlled trials were finally included and analyzed in this review. Compared with individuals treated with oseltamivir, this metaanalysis showed that participants treated with LHQW-C
had a shorter duration of (1) fever, weighted mean difference (WMD) = -4.65 (95% CI, -8.91 to -0.38; P = .030); (2) cough, WMD = -9.79 (95% CI, -14.61 to -4.97; P < .0001); (3) sore throat, WMD = -13.01 (95% CI, -21.76 to -4.27; P = .004); and (4) body ache, WMD = -16.68 (95% CI, -32.33 to -1.03; P = .040). The review also found that the efficacy of the 2 treatments on viral shedding was similar with WMD = -0.24 (95% CI, -4.79 to 4.31; P = .920). The authors conclude that LHQW-C was superior to oseltamivir in improving the symptoms of influenza A virus infection. (Altern Ther Health Med. 2014;20(2):25-30.)
Pan Zhao, MD, PhD, is an attending physician at the Clinical Trial Center, Beijing 302 Hospital, in Beijing, China. Haozhen Yang is an attending physician at the Liver Failure Therapy and Research Center, Beijing 302 Hospital. Hongyu Lv is an associate senior technician in the Medical Administration Department, Beijing 302 Hospital. Zhenman Wei is a professor at the Clinical Trial Center, Beijing 302 Hospital.
Corresponding author: Zhen-man Wei, MD E-mail address: email@example.com
ecently, a novel avian influenza virus, H7N9, has emerged in China, and it is much more transmissible to humans and much more difficult to track down than previous strains.1 As this virus shows, the threat of pandemic influenza has remained a major, international public health concern.2 Rapid antigenic evolution in an influenza virus increases the likelihood of emergence of novel strains.3 Under the circumstances, if vaccines are not yet available, treatment plays a crucial role in control of the disease. Oseltamivir, a neuraminidase inhibitor, has been widely used against influenza virus infection in the world, and it has exhibited potent efficacy in antiviral therapy.4-6 In China, traditional Chinese materia medica with a history of thousands of years has been used to treat various diseases.7-13 Lianhuaqingwen capsule (LHQW-C) is a traditional Chinese prescription composed of (1) zhimahuang—honey-fried herba ephedrae, (2) xingren—semen armeniacae amarum, (3) lianqiao—fructus forsythiae, (4) bohe—fructus forsythiae,
ALTERNATIVE THERAPIES, MAR/APR 2014 VOL. 20, 2 25
Zhao—Lianhuaqingwen vs Oseltamivir for Influenza A
-4. To share or copy this article. Embase. The quality of all selected articles was graded in accordance with the PRISMA Statement.14 Efficacy Measures Efficacy was measured using the following criteria: (1) duration of fever. and disagreement was resolved by discussion among investigators and reference to the original article. visit alternative-therapies.24 (95% CI. METHODS Search Strategy The authors searched PubMed. the authors have compared the efficacy and safety of LHQW-C and oseltamivir in treating influenza A virus infection.2 (Cochrane Collaboration. RESULTS Study Selection and Characteristics Searches resulted in 1963 unique articles. Table 3 shows the effect of LHQW-C versus oseltamivir on the duration from onset to negativity of viral RNA. 2012. Oxford. The total number of participants involved was 620. and (13) gancao—radix et rhizoma glycyrrhizae. The Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were also searched. Of these databases. and the China National Knowledge Infrastructure (CNKI) from the date of inception until December 31. and the difference between the 2 groups was statistically significant with WMD = -4. 20. (2) included an intervention group treated with LHQW-C and a control group treated with oseltamivir. Table 1 summarizes the main characteristics of the included RCTs.33 to -1. When several publications pertaining to a single study were identified. the random-effect method was used.79 (95% CI. drugrelated. the most complete publication was used. Use ISSN#1078-6791. no significant. P = . reported with 95% confidence intervals (CIs). United Kingdom). When heterogeneity was confirmed. MAR/APR 2014 VOL.65 (95% CI. including delirium or abnormal behavior. In this study.76 to -4. For inclusion. and decrease the development of serious complications. (12) hongjingtian—herba rhodiolae.004).920). The 5 included trials reported on the effects of LHQW-C compared with oseltamivir on viral shedding. the fixed26 ALTERNATIVE THERAPIES. The 5 included trials studied the effects of LHQW-C compared with oseltamivir on flu-like symptoms. and (3) duration of viral shedding.61 to -4.79 to 4. WMD = -9.31.68 (95% CI. 2 effect method was used to combine the results. the Wanfang database and CNKI provided literature in Chinese. (8) jinyinhua—flos lonicera japonicae.com. Figure 2 shows the forest plot of effect comparison of LHQW-C versus oseltamivir on duration of flu-like symptoms. Wanfang Data.05.This article is protected by copyright. Duration of Flu-like Symptoms. P = .21 However.97. Data analysis Data analysis was carried out using the Review Manager Software 4. No statistical differences existed between the 2 groups on duration from onset to negativity of viral ribonucleic acid (RNA). In the absence of statistically significant heterogeneity.0001). DISCUSSION It has been demonstrated that oseltamivir can prevent the release of progeny viral particles from infected host cells. occurred. WMD = -13. (2) duration of flu-like symptoms. P = .03.27.8 In these studies. P < . the search was designed using the following search terms: lianhuaqingwen capsule. 4 reported the time to sore throat alleviation. Viral Shedding. (2) sore throat. and (3) involved human participants. Table 2 shows the effect of LHQW-C versus oseltamivir on the time to defervescence. Quality Control Two investigators independently extracted data from each study using predefined forms. shorten the duration of influenza. -8. -21. Reference lists from retrieved documents were also searched. WMD = -16. oseltamivir. P = . Eligibility Criteria This meta-analysis included studies on individuals older than 3 years who were hospitalized with a clinical or laboratory diagnosis of influenza infection.38. The overall effect was tested using z scores. The estimated effect measures for treatment and control means were weighted mean difference (WMD).030). with WMD = -0. For the participants treated with LHQW-C and oseltamivir in the included studies. In this meta-analysis. and influenza. (6) yuxingcao—herba houttuyniae. Only 5 randomized controlled trials (RCTs) met the inclusion criteria.040). with significance set at P < . Significant heterogeneity was evaluated by the χ2 and I2 tests. The safety of treatment was also assessed.91 to -0. Safety. and 3 reported the time to body ache alleviation.14-18 Figure 1 shows the flowchart of the selection process. (9) shigao—gypsum fibrosum. the study must have (1) been a randomized. for example.20. 4 reported the time to cough alleviation. The China State Food and Drug Administration approved LHQW-C in 2004. and (3) body ache.01 (95% CI. -32.com (5) banlangen—radix isatidis. (7) guanzhong—dryopteris setosa. Clinical Outcomes Duration of Fever. To subscribe. please visit copyright. serious adverse events were observed. (11) guanghuoxiang—herba pogostemonis. of which 309 were in the LHQW-C group (treatment group) and 311 in the oseltamivir group (control group). no neuropsychiatric events. The treatment groups had shorter duration of (1) cough. controlled trial. -14. (10) dahuang—radix et rhizoma rhei.15-19 Shorter fever durations were shown for the LHQW-C groups compared with those for the oseltamivir groups. The 5 included studies reported the effects of LHQW-C compared with oseltamivir in reducing fever (defervescence). a major shortcoming of oseltamivir is the emergence of viral Zhao—Lianhuaqingwen vs Oseltamivir for Influenza A .
32) Mean (SD) in Oseltamivir 23. Abbreviations: LHQW-C = lianhuaqingwen capsule.47 -7. Use ISSN#1078-6791.80 -2. • unable to supply relevant data (15). 5 finally included in the meta-analysis Table 1. 20.19.70 (16.75 to -7.21 -7. please visit copyright.030.00) 21.65 95% Confidence Interval -9.13.38 Note: Test for heterogeneity—χ2 = 14.54) 30.21 (6. Table 2.32 (4.20 (16.16 (18.This article is protected by copyright.01 to 5.20 (21. • compared Lianhuaqingwen capsule treatment with other drug regimen (7).00 (14. Zhao—Lianhuaqingwen vs Oseltamivir for Influenza A ALTERNATIVE THERAPIES.91 to -2. visit alternative-therapies. Main Characteristics of the Included Trials Sample and Intervention Group Treated With LHQW-C (n = 309) 122 cases 60 cases 64 cases 25 cases 38 cases Group Treated With Oseltamivir (n = 311) 122 cases 74 cases 60 cases 25 cases 30 cases Literature Duan et al Ma et al 15 14 Study Design RCT. SD = standard deviation. MAR/APR 2014 VOL. blinding not confirmed RCT.09 -12. I2 = 71.08 to 5.com Figure 1.16 -8. 2 27 .8%. blinding not known RCT.70) 31.96 -4. double-blind RCT. blinding not known RCT. controlled trial.40 -0.56) 31. RCT = randomized.90 (12. Flowchart of the Study’s Selection Process 1963 studies identified through database 1725 excluded after title review 238 abstracts screened 202 excluded after abstract review 36 full-text articles screened Reasons for exclusion after full-text review: • not randomized controlled trial (9).00) WMD -6.00) 31.40 to 9.91 to -0.com.60) 33.60) 61.60) 62.11 0. To subscribe.00 (17.60 (21.00 -10. blinding not known Grade A B B B B Liu et al16 Li et al17 Geng et al18 Abbreviations: LHQW-C = lianhuaqingwen capsule. Effect of LHQW-C Versus Oseltamivir on the Time to Defervescence Literature Duan et al14 Geng et al18 Li et al17 Liu et al Ma et al Total 16 15 Mean (SD) in LHQW-C 17.00 -10. test for overall effect—z = 2. WMD = weighted mean difference. To share or copy this article. P = .
49 (-25.00) 117.20 (31.00 78.57) -10.65) -13.Figure 2.25) -19.45) 127. 20.27 16.65 (68.00 WMD (fixed) 95% CI -21.98 (P < .40 (-49. Use ISSN#1078-6791. -2. -2.20) 48. 2 Test for overall effect z = 3.20 (-11.28 28.41.58. To share or copy this article.75.05. -2.30) Liu et al16 36 67.27) Geng et al18 38 24. 12. -7.88 (10.10) 79.64) Total (95% CI) 157 Test for heterogeneity: χ = 23.00) 100.01 (-21.1% -100 -50 Favors treatment 0 50 Favors control 100 2 Zhao—Lianhuaqingwen vs Oseltamivir for Influenza A Test for overall effect z = 2.60 (14.80 (48.05) -7. 23.68 (14.20 (-31. I = 11.47 2.06.24) -12.05.2% -100 Favors treatment Favors control -50 0 50 100 2 ALTERNATIVE THERAPIES.68 (-13.com.20 (61.23) -9.0001) Outcome: Time to sore throat alleviation (h) n 30 25 40 69 164 2 Study or subcategory 46.53 (-34.61. 2.38 24.20 (16.32) Total (95% CI) 157 Test for heterogeneity: χ = 3.004) . -4.97) n Treatment mean (SD) Control mean (DS) WMD (fixed) 95% CI Weight % WMD (fixed) 95% CI Geng et al18 38 123. MAR/APR 2014 VOL. -4.92 (P < .00 (-26.67) Li et al 17 25 38.80) n Treatment mean (SD) Control mean (DS) WMD (fixed) 95% CI Weight % 29.0001). I = 87. To subscribe.56.52) -18.55 17.50 2.38.40 (31.90) Liu et al 16 44 98. please visit copyright.34) -7.20 (31. visit alternative-therapies.34).20) 116.com 28 Outcome: Time to cough alleviation (h) n 30 25 48 60 163 2 Study or subcategory 128.13.40) 110. df = 3 (P = .20 (15.40 (-18.88 (12.20) MA et al 15 50 103.20.20) MA et al 15 58 109.75 -5.12) Li et al 17 25 108. -17.79 (-14.78 100. Forest Plot of Comparison Between LHQW-C Versus Oseltamivir on Duration of Flu-like Symptoms This article is protected by copyright.43 (9.76.12 (49.94 (6. df = 3 (P = .60 (26.
18.21) -19.60 (31.06 -4.79 -16.56 (5. 5.20) 93.24 (-28.com Zhao—Lianhuaqingwen vs Oseltamivir for Influenza A Test for overall effect z = 2.66 to 1.42 to 35. P = .20) Total Note: Test for heterogeneity—χ2 = 5. SD = standard deviation.80) 144.40 (21.00 (14.20) 100. test for overall effect—z = 0.01.88) Li et al 17 25 27.79 to 15.Figure 2.00 (50.59.77 41. (continued) Outcome: Time to body ache alleviation (h) n 30 25 9 64 2 Study or subcategory 45. MAR/APR 2014 VOL.6%. WMD = weighted mean difference.60 (40.31 Literature Mean (SD) in LHQW-C Duan et al14 108.60 7. To subscribe.80) Ma et al 15 139. I = 89.40) 69.00 (36. df = 2 (P = .20 (-43. ALTERNATIVE THERAPIES. 29 .20) Liu et al 16 10 50.81 37.40) Liu et al 16 98.60) Total (95% CI) 73 Test for heterogeneity: χ = 19.10.03) n Treatment mean (SD) Control mean (DS) WMD (fixed) 95% CI Weight % WMD (fixed) 95% CI Geng et al18 38 20.com.19) -16.32 (6.00 (34.60 (11.95.80 -0. -1.42 -25. please visit copyright. To share or copy this article.24 9.00 20. 20. 2 Abbreviations: LHQW-C = lianhuaqingwen capsule.20 (19.40.40 (40.80 -4. -22.48) 33.40 (43.57 to 19. Effect of LHQW-C Versus Oseltamivir on Duration From Onset to Negativity of Viral RNA Mean (SD) in Oseltamivir 101.0001). Use ISSN#1078-6791.920.40) 4.33.00) 98.50 (17.30) -5.90 (-14. I2 = 49.004) Table 3. visit alternative-therapies.17 -10.7% -100 Favors treatment Favors control -50 0 50 100 2 This article is protected by copyright. 2.62 -9. RNA = ribonucleic acid.68 (-32.00) Li et al 17 108.79 to 4.00 WMD 95% Confidence Interval -1.09 (P < .
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