Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial
Several Ephedra Herb-containing Kampo medicines are common initial treatments for various infections; however, the ephedrine alkaloids in Ephedra Herb can cause side effects by stimulating adrenergic receptors. Accordingly, an ephedrine alkaloids-free Ephedra Herb Extract (EFE) has been developed. T...
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MDPI AG
2025-03-01
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| author | Hiroshi Odaguchi Sumiko Hyuga Mariko Sekine Hirofumi Michimae Masashi Hyuga Nahoko Uchiyama Masashi Uema Yuji Kumagai Yusuke Suzuki Shigeki Nabeshima Norio Omagari Yohei Doi Kunihiro Yamaoka Koji Miyazaki Susumu Fuji Yoshihiro Umezawa Shiho Kodera Hirotaka Nagashima Wataru Hirose Yukihiro Goda |
| author_facet | Hiroshi Odaguchi Sumiko Hyuga Mariko Sekine Hirofumi Michimae Masashi Hyuga Nahoko Uchiyama Masashi Uema Yuji Kumagai Yusuke Suzuki Shigeki Nabeshima Norio Omagari Yohei Doi Kunihiro Yamaoka Koji Miyazaki Susumu Fuji Yoshihiro Umezawa Shiho Kodera Hirotaka Nagashima Wataru Hirose Yukihiro Goda |
| author_sort | Hiroshi Odaguchi |
| collection | DOAJ |
| description | Several Ephedra Herb-containing Kampo medicines are common initial treatments for various infections; however, the ephedrine alkaloids in Ephedra Herb can cause side effects by stimulating adrenergic receptors. Accordingly, an ephedrine alkaloids-free Ephedra Herb Extract (EFE) has been developed. This study aimed to evaluate whether EFE can be used effectively and safely in patients with mild coronavirus disease 2019 (COVID-19). We randomized patients with mild COVID-19 to receive EFE equivalent to 6 g of Ephedra Herb per day or a placebo for 14 days. The primary efficacy endpoint was the non-aggravation rate up to Day 15. We allocated 41 and 40 patients to the EFE and placebo groups, respectively. All participants were included in the mITT and safety analysis populations [male ratio, mean age: 31.7%, 42.0 years (EFE); 17.5%, 43.2 years (placebo)]. The non-aggravation rate up to Day 15 for the primary endpoint was 100.0% and 94.6% in the EFE and placebo group, respectively, with no between-group difference. The number of days to the improvement in nausea symptoms was significantly shorter in the EFE group. One patient in the placebo group discontinued the trial due to a side effect. Although EFE demonstrated safety in patients with mild COVID-19, it did not show superior efficacy compared to placebo for symptoms other than nausea. |
| format | Article |
| id | doaj-art-bfdd2d19d38146cd98be9d17e3d1a70c |
| institution | OA Journals |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-bfdd2d19d38146cd98be9d17e3d1a70c2025-08-20T01:49:05ZengMDPI AGMicroorganisms2076-26072025-03-0113364110.3390/microorganisms13030641Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative TrialHiroshi Odaguchi0Sumiko Hyuga1Mariko Sekine2Hirofumi Michimae3Masashi Hyuga4Nahoko Uchiyama5Masashi Uema6Yuji Kumagai7Yusuke Suzuki8Shigeki Nabeshima9Norio Omagari10Yohei Doi11Kunihiro Yamaoka12Koji Miyazaki13Susumu Fuji14Yoshihiro Umezawa15Shiho Kodera16Hirotaka Nagashima17Wataru Hirose18Yukihiro Goda19Oriental Medicine Research Center, School of Pharmacy, Kitasato University, Tokyo108-8641, JapanOriental Medicine Research Center, School of Pharmacy, Kitasato University, Tokyo108-8641, JapanKitasato University Kitasato Institute Hospital, Shirokane Campus, Tokyo 108-8642, JapanDepartment of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo 108-8641, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanKitasato University Kitasato Institute Hospital, Shirokane Campus, Tokyo 108-8642, JapanKitasato University Kitasato Institute Hospital, Shirokane Campus, Tokyo 108-8642, JapanDepartment of General Medicine, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, JapanDisease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo 162-8655, JapanSchool of Medicine, Fujita Health University, Toyoake 470-1192, JapanDepartment of Rheumatology and Infectious Diseases, Kitasato University Hospital, Sagamihara 252-0375, JapanDepartment of General Internal Medicine, Tokai University Hachioji Hospital, Tokyo 192-0032, JapanOgikubo Hospital, Tokyo 167-0035, JapanDenenchofu Family Clinic, Tokyo 145-0071, JapanTokyo Metropolitan Ebara Hospital, Tokyo 145-0065, JapanTokyo Center Clinic, Tokyo 192-0397, JapanHirose Clinic, Tokorozawa 359-1111, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanSeveral Ephedra Herb-containing Kampo medicines are common initial treatments for various infections; however, the ephedrine alkaloids in Ephedra Herb can cause side effects by stimulating adrenergic receptors. Accordingly, an ephedrine alkaloids-free Ephedra Herb Extract (EFE) has been developed. This study aimed to evaluate whether EFE can be used effectively and safely in patients with mild coronavirus disease 2019 (COVID-19). We randomized patients with mild COVID-19 to receive EFE equivalent to 6 g of Ephedra Herb per day or a placebo for 14 days. The primary efficacy endpoint was the non-aggravation rate up to Day 15. We allocated 41 and 40 patients to the EFE and placebo groups, respectively. All participants were included in the mITT and safety analysis populations [male ratio, mean age: 31.7%, 42.0 years (EFE); 17.5%, 43.2 years (placebo)]. The non-aggravation rate up to Day 15 for the primary endpoint was 100.0% and 94.6% in the EFE and placebo group, respectively, with no between-group difference. The number of days to the improvement in nausea symptoms was significantly shorter in the EFE group. One patient in the placebo group discontinued the trial due to a side effect. Although EFE demonstrated safety in patients with mild COVID-19, it did not show superior efficacy compared to placebo for symptoms other than nausea.https://www.mdpi.com/2076-2607/13/3/641SARS-CoV-2COVID-19EFEDB-RCTKampo medicinecrude drug |
| spellingShingle | Hiroshi Odaguchi Sumiko Hyuga Mariko Sekine Hirofumi Michimae Masashi Hyuga Nahoko Uchiyama Masashi Uema Yuji Kumagai Yusuke Suzuki Shigeki Nabeshima Norio Omagari Yohei Doi Kunihiro Yamaoka Koji Miyazaki Susumu Fuji Yoshihiro Umezawa Shiho Kodera Hirotaka Nagashima Wataru Hirose Yukihiro Goda Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial Microorganisms SARS-CoV-2 COVID-19 EFE DB-RCT Kampo medicine crude drug |
| title | Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial |
| title_full | Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial |
| title_fullStr | Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial |
| title_full_unstemmed | Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial |
| title_short | Safety and Efficacy of Ephedrine Alkaloids-Free Ephedra Herb Extract (EFE) for Mild COVID-19: A Double-Blind, Placebo-Controlled, Randomized Comparative Trial |
| title_sort | safety and efficacy of ephedrine alkaloids free ephedra herb extract efe for mild covid 19 a double blind placebo controlled randomized comparative trial |
| topic | SARS-CoV-2 COVID-19 EFE DB-RCT Kampo medicine crude drug |
| url | https://www.mdpi.com/2076-2607/13/3/641 |
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