26
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A structured summary of a study protocol for a multi-center, randomized controlled trial (RCT) of COVID-19 prevention with Kampo medicines (Integrative Management in Japan for Epidemic Disease by prophylactic study: IMJEDI P1 study)

      letter

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          We aimed to test our hypothesis that traditional Japanese (Kampo) medicine, hochuekkito (Hochu-ekki-to: HET) has a preventive effect for the symptoms on COVID-19.

          Trial design

          The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator sponsored, two-arm study.

          Participants

          Six thousand participants will be recruited from healthy hospital workers in 7 Japanese University Hospitals.

          Inclusion criteria:

          1. Age from 20 to 75 years old at the time of registration

          2. Asymptomatic and body temperature below 37°C at the time of registration

          3. Capable of eating orally

          Exclusion criteria:

          1. Previous upper respiratory inflammation due to viral infection (including suspected COVID-19)

          2. Taking immunosuppressants

          3. Allergic to the Kampo medicines used in this study

          4. History of hypokalaemia, severe hypertension, severe liver dysfunction, and interstitial pneumonia

          5. Regularly taking other Kampo medicines

          6. Pregnant or possibly pregnant

          7. Participating in other research

          8. Judged to be unsuitable for this study by the doctor in charge

          Intervention and comparator

          Kampo group: participants receive HET in 9 tablets 2 times per day for 8 weeks.

          Control group: participants receive placebo in the same dosage as the Intervention group - 9 tablets 2 times per day for 8 weeks. Placebo tablets are identical in appearance and package to HET. Taste of placebo is different from that of HET.

          The Ohsugi Pharmaceutical Co. Ltd, Osaka, Japan manufactured the placebo and HET.

          Main outcomes

          Primary outcome: Number of patients with a SARS-CoV-2 RNA by ploymerase chain reaction (PCR) positive result with at least one symptom (fever, cough, sputum, malaise, shortness of breath) during the 12-week study period (including the 4-week observation period after oral administration).

          Secondary outcomes:

          1. Period from infection to onset

          2. Period from the appearance of symptoms to the disappearance of PCR positive

          3. Number of days until the appearance or improvement of symptoms

          4. Severe stage: presence of hospitalization

          5. Shock stage: ICU management required for mechanical ventilation, shock vitals or failure of organ(s) other than lungs

          Safety endpoints include numbness in the hands and/or feet, edema, skin rash or other allergic symptoms, and gastric discomfort.

          Randomisation

          Patients are randomized (1:1 ratio) to each group using minimization implemented with the Electric data capture system (DATATRAK Enterprise Cloud), with balancing of the arms with age range (under 50 years of age or not) and having a history of risk factors for COVID-19 (cardiovascular disease, hypertension, diabetes, respiratory diseases).

          Blinding (masking)

          Only participants will be randomized.

          Numbers to be randomised (sample size)

          The main research hypothesis of this study is that Kampo medicines significantly prevent the onset of COVID-19. It is assumed that the infection rate before the administration of the drug under consideration will be 0% and that the incidence of COVID-19 thereafter will be 2- 3%, of which 70%-80% will show symptoms of COVID-19. Assuming that the pharmaceutical effect of the drug will be effective in 50% of patients and that the incidence rates in the placebo and drug groups will be 1.4%-2.4% and 0.7%-1.2%, respectively, the placebo is calculated at 2%, and the study drug at 1%. Since the frequency of verification is low and the number of cases will be large, we set a total of 10 analyses (9 interim analyses and a final analysis). Since the number of cases at the time of the final analysis will be 4,986 under the conditions of α = 0.05 and a power of 80% by the Peto method. We set at 600 cases in each interim analysis with an estimated dropout rate of 16.9%. Finally, the total number of cases is set to 6,000 with 3,000 in the placebo group and 3,000 in the HET group.

          Trial status

          Protocol version 1.3 of October 23rd , 2020. Recruitment start (expected): December 1 st, 2020. Recruitment finish (expected): December 31 st, 2022.

          Trial registration

          This trial is registered in the Japan Registry of Clinical Trials (jRCT) ( jRCTs031200150) on 14 October 2020.

          Full protocol

          The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13063-020-04939-2.

          Related collections

          Author and article information

          Contributors
          tnamiki@faculty.chiba-u.jp
          takayama@med.tohoku.ac.jp
          ryutaro.arita.q4@dc.tohoku.ac.jp
          t-ishi23@med.tohoku.ac.jp
          kainuma@gim.med.kyushu-u.ac.jp
          makino@phar.nagoya-cu.ac.jp
          mimura@a7.keio.jp
          tetta213@keio.jp
          t-nogami@tsc.u-tokai.ac.jp
          arai@tokai-u.jp
          juichi@med.nagoya-u.ac.jp
          kouichirou.tanaka@med.toho-u.ac.jp
          nakaeh@doc.med.akita-u.ac.jp
          igari_h@chiba-u.jp
          yoshihito.ozawa@chiba-u.jp
          shiko_yuki@chiba-u.jp
          ykawasaki@chiba-u.jp
          mshknezu@gmail.com
          ito.takashi8627@gmail.com
          Journal
          Trials
          Trials
          Trials
          BioMed Central (London )
          1745-6215
          6 January 2021
          6 January 2021
          2021
          : 22
          : 23
          Affiliations
          [1 ]GRID grid.136304.3, ISNI 0000 0004 0370 1101, Department of Japanese-Oriental (Kampo) Medicine, Graduate School of Medicine, , Chiba University, ; 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670 Japan
          [2 ]GRID grid.412757.2, ISNI 0000 0004 0641 778X, Department of Kampo Medicine, , Tohoku University Hospital, ; 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
          [3 ]GRID grid.412757.2, ISNI 0000 0004 0641 778X, Department of Education and Support for Regional Medicine, , Tohoku University Hospital, ; 1- 1, Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
          [4 ]GRID grid.69566.3a, ISNI 0000 0001 2248 6943, Department of Kampo and Integrative Medicine, , Tohoku University Graduate School of Medicine, ; 1-2, Seiryo-machi, Aoba-ku, Sendai, 980-8575 Japan
          [5 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Community Medicine Education Unit, Graduate School of Medical Science, , Kyushu University, ; 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
          [6 ]GRID grid.260433.0, ISNI 0000 0001 0728 1069, Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, , Nagoya City University, ; 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 467-8603 Japan
          [7 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Department of Neuropsychiatry, , Keio University School of Medicine, ; 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
          [8 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Center for Kampo Medicine, , Keio University School of Medicine, ; 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
          [9 ]GRID grid.265061.6, ISNI 0000 0001 1516 6626, Department of Kampo Medicine, , Tokai University School of Medicine, ; 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan
          [10 ]GRID grid.27476.30, ISNI 0000 0001 0943 978X, Department of General Medicine/Family & Community Medicine, , Nagoya University Graduate School of Medicine, ; 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan
          [11 ]GRID grid.265050.4, ISNI 0000 0000 9290 9879, Department of Traditional Medicine, Faculty of Medicine, , Toho University, ; 5-21-16, Omorinishi, Ota-ku, Tokyo, 143-8540 Japan
          [12 ]GRID grid.251924.9, ISNI 0000 0001 0725 8504, Department of Emergency and Critical Care Medicine, , Akita University Graduate School of Medicine, ; 44-2 Hasunuma Hiroomote, Akita, 010-8543 Japan
          [13 ]GRID grid.136304.3, ISNI 0000 0004 0370 1101, Department of Infectious Diseases, Chiba University Hospital, School of Medicine, , Chiba University, ; 1-8-1, Inohana, Chuo-ku, Chiba, 260-8677 Japan
          [14 ]GRID grid.411321.4, ISNI 0000 0004 0632 2959, Biostatistics Section, Clinical Research Center, , Chiba University Hospital, ; 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677 Japan
          [15 ]GRID grid.443371.6, ISNI 0000 0004 1784 6918, Faculty of Nursing, , Japanese Red Cross College of Nursing, ; Tokyo, 150-0012 Japan
          [16 ]Akashi Clinic Kanda, 3-8, Kandaogawamachi, Chiyodaku, Tokyo, 101-0052 Japan
          Author information
          http://orcid.org/0000-0003-1047-7999
          Article
          4939
          10.1186/s13063-020-04939-2
          7787232
          33407828
          848404ca-d4c1-4b38-a93f-95c5e11e5725
          © The Author(s) 2020

          Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

          History
          : 15 November 2020
          : 30 November 2020
          Funding
          Funded by: The Japan Society of Oriental Medicine
          Categories
          Letter
          Custom metadata
          © The Author(s) 2021

          Medicine
          covid-19,randomized controlled trial,protocol,kampo medicines,prophylactic study
          Medicine
          covid-19, randomized controlled trial, protocol, kampo medicines, prophylactic study

          Comments

          Comment on this article