Original Research16 August 2011
A Randomized Trial
    Author, Article, and Disclosure Information

    This article has been corrected. The original version (PDF) is appended to this article as a supplement.

    Background:

    Observational studies from Asia suggest that maxingshigan–yinqiaosan may be effective in the treatment of acute H1N1 influenza.

    Objective:

    To compare the efficacy and safety of oseltamivir and maxingshigan–yinqiaosan in treating uncomplicated H1N1 influenza.

    Design:

    Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194)

    Setting:

    Eleven hospitals from 4 provinces in China.

    Patients:

    410 persons aged 15 to 69 years with laboratory-confirmed H1N1 influenza.

    Intervention:

    Oseltamivir, 75 mg twice daily; maxingshigan–yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan–yinqiaosan; or no intervention (control). Interventions and control were given for 5 days.

    Measurements:

    Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction.

    Results:

    Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan–yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan–yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan–yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan–yinqiaosan reported nausea and vomiting.

    Limitations:

    Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding.

    Conclusion:

    Oseltamivir and maxingshigan–yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan–yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection.

    Primary Funding Source:

    Beijing Science and Technology Project and Beijing Nova Program.

    References

    • 1. Centers for Disease Control and Prevention (CDC)Swine influenza A (H1N1) infection in two children—Southern California, March-April 2009. MMWR Morb Mortal Wkly Rep2009;58:400-2. [PMID: 19390508] MedlineGoogle Scholar
    • 2. Centers for Disease Control and Prevention (CDC)Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep2009;58:467-70. [PMID: 19444150] MedlineGoogle Scholar
    • 3. Centers for Disease Control and Prevention (CDC)Update: infections with a swine-origin influenza A (H1N1) virus—United States and other countries, April 28, 2009. MMWR Morb Mortal Wkly Rep2009;58:431-3. [PMID: 19407737] MedlineGoogle Scholar
    • 4. Pandemic (H1N1) 2009—update 94. Geneva: World Health Organization; 1 April 2010. Accessed at www.who.int/csr/don/2010_04_01/en/index.html on 9 April 2010. Google Scholar
    • 5. Cao BLi XWMao YWang JLu HZChen YSet alNational Influenza A Pandemic (H1N1) 2009 Clinical Investigation Group of ChinaClinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med2009;361:2507-17. [PMID: 20007555] CrossrefMedlineGoogle Scholar
    • 6. Jain SKamimoto LBramley AMSchmitz AMBenoit SRLouie Jet al2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation TeamHospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med2009;361:1935-44. [PMID: 19815859] CrossrefMedlineGoogle Scholar
    • 7. Domínguez-Cherit GLapinsky SEMacias AEPinto REspinosa-Perez Lde la Torre Aet alCritically Ill patients with 2009 influenza A(H1N1) in Mexico. JAMA2009;302:1880-7. [PMID: 19822626] CrossrefMedlineGoogle Scholar
    • 8. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 Influenza and Other Influenza Viruses. Geneva: World Health Organization; 20 August 2009. Accessed at www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf on 10 June 2011. Google Scholar
    • 9. Uyeki TAntiviral treatment for patients hospitalized with 2009 pandemic influenza A (H1N1). N Engl J Med2009;361:110. [PMID: 19923564] CrossrefMedlineGoogle Scholar
    • 10. Baz MAbed YPapenburg JBouhy XHamelin MEBoivin GEmergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis [Letter]. N Engl J Med2009;361:2296-7. [PMID: 19907034] CrossrefMedlineGoogle Scholar
    • 11. Chan KChinese medicinal materials and their interface with Western medical concepts. J Ethnopharmacol2005;96:1-18. [PMID: 15588645] CrossrefMedlineGoogle Scholar
    • 12. Wang JCheng SHZhang JYA systematic review of chuanhuning for acute respiratory tract infections. Chinese Archives of Traditional Chinese Medicine2007;25:2200-3. Google Scholar
    • 13. Chen NRen L[Modern pharmacology research and clinical use of maxingshigan]. Academic Journal of Guang Dong College of Pharmacy2004;:545-6. Google Scholar
    • 14. Huang JMChen DPYang LP[The immunomodulating effects of maxingshigan on asthma mice models]. Journal of Fujian Traditional Chinese Medicine2003;34:38-9. Google Scholar
    • 15. Chinese Pharmacopoeia Commission[Pharmacopoeia of the People's Republic of China]. Beijing: People's Medical Publishing House; 2005. Google Scholar
    • 16. World Health Organization. CDC Protocol of Realtime RTPCR for Influenza A (H1N1). Geneva: World Health Organization; 28 April 2009. Accessed at www.who.int/csr/resources/publications/swineflu/CDCRealtimeRTPCR_SwineH1Assay-2009_20090430.pdf on 10 June 2011. Google Scholar
    • 17. Nicholson KGAoki FYOsterhaus ADTrottier SCarewicz OMercier CHet alEfficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet2000;355:1845-50. [PMID: 10866439] CrossrefMedlineGoogle Scholar
    • 18. Treanor JJHayden FGVrooman PSBarbarash RBettis RRiff Det alEfficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA2000;283:1016-24. [PMID: 10697061] CrossrefMedlineGoogle Scholar
    • 19. Patel KKay RRowell LComparing proportional hazards and accelerated failure time models: an application in influenza. Pharm Stat2006;5:213-24. [PMID: 17080754] CrossrefMedlineGoogle Scholar
    • 20. Cheng JTReview: drug therapy in Chinese traditional medicine. J Clin Pharmacol2000;40:445-50. [PMID: 10806595] CrossrefMedlineGoogle Scholar
    • 21. Zhao WNLu FGZhang WZhu YWHe YCEffect of maxing shigan decoction and its alteration on mice T-cell subpopulation exposed to influenza virus A. Practical Preventive Medicine2007;14:178-280. Google Scholar
    • 22. Guo FHe YCXiao ZZWu CRZhang WLi Set alStudy on effect target of maxing shigan decoction on anti-influenza virus A in vitro. Journal of Traditional Chinese Medicine University of Hunan2008;28:5-9. Google Scholar
    • 23. Zhang WLu FGHe YCXiao ZZLu XHZhu YWet alExperimental study on effect of maxing shigan decoction on anti-influenza virus A in vitro. Practical Preventive Medicine2007;14:1351-3. Google Scholar
    • 24. Poon PMWong CKFung KPFong CYWong ELLau JTet alImmunomodulatory effects of a traditional Chinese medicine with potential antiviral activity: a self-control study. Am J Chin Med2006;34:13-21. [PMID: 16437735] CrossrefMedlineGoogle Scholar
    • 25. Chow MSChang QZuo JHerb-drug interaction involving oseltamivir and Chinese medicine formula [Abstract]. FASEB J2008;22 Suppl 1136.24. CrossrefGoogle Scholar
    • 26. U.S. Food and Drug Administration. Dietary supplements containing ephedrine alkaloids. 22 August 2006. Accessed at www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152388.htm on 10 June 2011. Google Scholar
    • 27. Health Canada requests recall of certain products containing ephedra/ephedrine. 6 February 2007. Accessed at www.preventivehealthtoday.com/alerts/hc_ephedra_020109.html on 10 June 2011. Google Scholar
    • 28. Hallas JBjerrum LStøvring HAndersen MUse of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study. Am J Epidemiol2008;168:966-73. [PMID: 18756018] CrossrefMedlineGoogle Scholar
    • 29. Andraws RChawla PBrown DLCardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis2005;47:217-25. [PMID: 15991150] CrossrefMedlineGoogle Scholar
    • 30. Haller CABenowitz NLAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med2000;343:1833-8. [PMID: 11117974] CrossrefMedlineGoogle Scholar
    • 31. Soni MGCarabin IGGriffiths JCBurdock GASafety of ephedra: lessons learned. Toxicol Lett2004;150:97-110. [PMID: 15068827] CrossrefMedlineGoogle Scholar
    • 32. Yan YZhan LChen ZKang C[Changes of ephedrine and pseudoephedrine content in Herba Ephedrae before and after honeybaking]. West China Journal of Pharmaceutical Sciences2007;22:559-61. Google Scholar
    • 33. Moscona ANeuraminidase inhibitors for influenza. N Engl J Med2005;353:1363-73. [PMID: 16192481] CrossrefMedlineGoogle Scholar
    • 34. Jefferson TJones MDoshi PDel Mar CNeuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ2009;339:b5106. [PMID: 19995812] CrossrefMedlineGoogle Scholar
    • 35. Dharan NJGubareva LVMeyer JJOkomo-Adhiambo MMcClinton RCMarshall SAet alOseltamivir-Resistance Working GroupInfections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA2009;301:1034-41. [PMID: 19255110] CrossrefMedlineGoogle Scholar