Exploring the Safety, Effectiveness, and Cost-Effectiveness of a Chinese Patent Medicine (Fufang E'jiao Syrup) for Alleviating Cancer-Related Fatigue: A Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Multicenter Trial

Zhuo Song, Ling-Yun Sun, Shan-Shan Gu, Xiao-Shu Zhu, He-Zheng Lai, Fang Lu, Ning Cui, Qiong-Yang Li, Yu Wu, Yun Xu, Zhuo Song, Ling-Yun Sun, Shan-Shan Gu, Xiao-Shu Zhu, He-Zheng Lai, Fang Lu, Ning Cui, Qiong-Yang Li, Yu Wu, Yun Xu

Abstract

Objective: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial.

Methods/design: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained.

Discussion: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS.

Trial registration: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.

Keywords: Chinese patent medicine; Fufang E’jiao syrup; cancer-related fatigue; multicenter; randomized-controlled trial; traditional Chinese medicine.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow chart of the trial procedure. Abbreviations: FFEJS, Fufang E’Jiao syrup; CRF, cancer related fatigue; RPFS-CV, revised piper fatigue scale of Chinese version; QoL, quality of life; ESAS, edmonton symptom assessment scale; FACT-F, functional assessment of cancer therapy; AEs, adverse events; EQ-5D-5L, Euroqol scale of 5 dimensions at 5 levels.
Figure 2.
Figure 2.
Two-sample T-test power analysis.

References

    1. Fabi A, Bhargava R, Fatigoni S, et al.. ESMO Guidelines Committee. Cancer-related fatigue: ESMO clinical practice guidelines for diagnosis and treatment. Ann Oncol. 2020;31:713-723.
    1. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12(suppl 1):4-10.
    1. Bower JE, Ganz PA, Desmond KA, et al.. Fatigue in long-term breast carcinoma survivors. A longitudinal investigation. Cancer. 2006;106:751-758.
    1. Baker F, Denniston M, Smith T, West MM. Adult cancer survivors: how are they faring. Cancer. 2005;104(suppl 11):2565-2576.
    1. Semiha A, Canan Kas G. Investigation of the relationship among fatigue, self-efficacy and quality of life during chemotherapy in patients with breast, lung or gastrointestinal cancer. Eur J Cancer Care (Engl). 2019;28:e12898.
    1. Siegel K, Lekas HM, Maheshwari D. Causal attributions for fatigue by older adults with advanced cancer. J Pain Symptom Manage. 2012;44:52-63.
    1. Lai S. Cancer related fatigue and cancer cachexia are the consequence of endocrine failure caused by persisten stress. Med Hypotheses. 2019;123:60-62.
    1. Medysky ME, Temesi J, Culos-Reed SN, Millet GY. Exercise, sleep and cancer-related fatigue: are they related. Neurophysiol Clin. 2017;47:111-122.
    1. Mücke M, Mochamat Cuhls H, et al.. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2015;2015:CD006788.
    1. Lundt A, Jentschke E. Long-term changes of symptoms of anxiety, depression, and fatigue in Cancer patients 6 months after the end of yoga therapy. Integr Cancer Ther. 2019;18:1534735418822096.
    1. Gheyasi F, Baraz S, Malehi A, Ahmadzadeh A, Salehi R, Vaismoradi M. Effect of the walking exercise program on cancer-related fatigue in patients with acute myeloid leukemia undergoing chemotherapy. Asian Pac J Cancer Prev. 2019;20:1661-1666.
    1. Mustian KM, Alfano CM, Heckler C, et al.. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol. 2017;3:961-968.
    1. Kinkead B, Schettler PJ, Larson ER, et al.. Massage therapy decreases cancer-related fatigue: results from a randomized early phase trial. Cancer. 2018;124:546-554.
    1. Cheng CS, Chen LY, Ning ZY, et al.. Acupuncture for cancer-related fatigue in lung cancer patients: a randomized, double blind, placebo-controlled pilot trial. Support Care Cancer. 2017;25:3807-3814.
    1. Yu T, Zou XJ, Liu HT, et al.. Syndrome of Chinese medicine in cancer related fatigue: a literature reviewer. J Tradit Chin Med. 2017;58:2151-2154.
    1. Xu YC, Chen YZ, Li PP, Wang XS. Ren shen yangrong tang for fatigue in cancer survivors: a phase I/II open-label study.J Altern Complement Med. 2015;21:281-287.
    1. Jeong JS, Ryu BH, Kim JS, Park JW, Choi WC, Yoon SW. Bojungikki-tang for cancer-related fatigue: a pilot randomized clinical trial.Integr Cancer Ther. 2010;9:331-338.
    1. Xiao Z, Hu L, Lin J, et al.. Efficacy and safety of Jianpishengsui for chemotherapy-related fatigue in patients with non-small cell lung cancer: study protocol for a randomized placebo-controlled clinical trial. Trials. 2020;21:94.
    1. Li X, Zhang Y, Hong Z, et al.. Transcriptome profiling analysis reveals the potential mechanisms of three bioactive ingredients of Fufang E’jiao jiang during chemotherapy-induced myelosuppression in mice. Front Pharmacol. 2018;9:616.
    1. Song T, Liang SP, Wang HQ, et al.. Clinical effect on compound Ejiao Jiang treating chemotherapy-induced myelosuppression. J Tianjin Med Univ. 2016;1:24-27.
    1. Wei YS, Wang BL, Zhang JH, et al.. Observation on the efficacy of compound Ejiao Jiang combined with chemotherapy in the treatment of advanced colorectal cancer. Mod J Integr Tradit Chin West Med. 2017;26:3912-3914.
    1. Li X, Chen XY, Hou L, et al.. Curative effect of Fufang Ejiao Jiang on cancer related anemia. J Beijing Univ Tradit Chin Med. 2013;20:27-30.
    1. Li N, Chen XY, Li X, et al.. The clinical observation to the effects of fufang e’jiao jiang on cancer-related fatigue. Chin J Tradit Chin Med. 2013;28:565-567.
    1. Di ZQ, Hu JF, Zhang L, et al.. Study on hematopoiesis, antifatigue and hemostatic effects of Asini Corii Colla. Drug Eval Res. 2018;41:562-566.
    1. National Center for Complementary and Integrative Health (NCCIH). Use of complementary health approaches in the US. 2017. Accessed March 29, 2018.
    1. Arring NM, Millstine D, Marks LA, Nail LM. Ginseng as a treatment for fatigue: a systematic review.J Altern Complement Med. 2018;24:624-633.
    1. Amin MB, Greene FL, Edge SB, et al.. AJCC Cancer Staging Manual. 8th ed. Springer; 2016.
    1. Center of health statistics and information, ministry of health in China and International cooperation center for disease classification of union hospital, Beijing. International classification of diseases (ICDl0) application guidelines. Peking union medical college press; 2001:58.
    1. Song J, Shin SM, Kim H. Efficacy and safety of HT048 and HT077 for body fat and weight loss in overweight adults: a study protocol for a double-blind, randomized, placebo-controlled trial. Medicine. 2019;98:e17922.
    1. Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM. The revised piper fatigue scale: psychometric evaluation in women with breast cancer. Oncol Nurs Forum. 1998;25:677-684.
    1. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer-related fatigue. Oncologist. 2007;12(suppl 1):22-34.
    1. Brenne E, Loge JH, Lie H, et al.. The edmonton symptom assessment system: poor performance as screener for major depression in patients with incurable cancer. Palliat Med. 2016;30:587-598.
    1. Ishikawa NM, Thuler LC, Giglio AG, et al.. Validation of the portuguese version of functional assessment of cancer therapy-fatigue (FACT-F) in brazilian cancer patients. Support Care Cancer. 2010;18:481-490.
    1. Jin D, Huang WJ, Meng X, et al.. Chinese herbal medicine tangshen formula treatment for type 2 diabetic kidney disease in the early stage: study protocol for a randomized controlled trial. Trials. 2019;20:756.
    1. National Cancer Institute. Common terminology criteria for adverse events v4.0. May 29, 2009. NIH publication # 09-7473.
    1. Liu GG, Wu H, Li M, Gao C, Luo N. Chinese time trade-off values for EQ-5D health states. Value Health. 2014;17:597-604.
    1. Shida T, Endo Y, Shiraishi T, et al.. Economic evaluation of mFOLFOX6-based first-line regimens for unresectable advanced or recurrent colorectal cancer using clinical decision analysis. Yakugaku Zasshi. 2018;138:83-90.
    1. Fong DY, Ho JW, Hui BP, et al.. Physical activity for cancer survivors: meta-analysis of randomised controlled trials. BMJ. 2012;344:e70.
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, et al.. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.
    1. Cheng CW, Wu TX, Shang HC, et al.. CONSORT extension for chinese herbal medicine formulas 2017: recommendations, explanation, and elaboration. Ann Intern Med. 2017;167(2):112-121.
    1. Wang Y, Xu RR. The research progress on the application of fufang e’jiao jiang. Chin J Clin Ration Drug Use. 2011;4:151-153.
    1. Maoxuan L, Haining T, Xinke Z, et al.. Hematopoietic effects and mechanisms of Fufang E’jiao Jiang on radiotherapy and chemotherapy-induced myelosuppressed mice. J Ethnopharmacol. 2014;152:575-584.
    1. Cella D, Kallich J, McDermott A, Xu X. The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials. Ann Oncol. 2004;15:979.
    1. Hoskin PJ, Robinson M, Slevin N, Morgan D, Harrington K, Gaffney C. Effect of epoetin alfa on survival and cancer treatment-related anemia and fatigue in patients receiving radical radiotherapy with curative intent for head and neck cancer. J Clin Oncol. 2009;27:5751-5756.
    1. Tang XD, Bian LQ, Gao R. Exploration into the preparation of placebos used in Chinese medicinal clinical trial. Chin J Integr Tradit West Med. 2009;29:656-658.
    1. Kamath J, Feinn R, Winokur A. Thyrotropin-releasing hormone as a treatment for cancer-related fatigue: a randomized controlled study. Support Care Cancer. 2012;20:1745-1753.
    1. Yang G, Zhang H, Gan Z, Fan Y, Gu W, Ling C. Discrepant views of oncologists and cancer patients on complementary and alternative medicine in a Chinese general hospital. Integr Cancer Ther. 2018;17:451-457.
    1. Sun L, Xu Y, Zhang T, Yang Y. Impact of the COVID-19 outbreak on adjuvant chemotherapy for patients with stage II or III colon cancer: experiences from a multicentre clinical trial in China. Curr Oncol. 2020;27:159-162.
    1. Psotka MA, Abraham WT, Fiuzat M, et al.. Conduct of clinical trials in the era of COVID-19: JACC scientific expert panel. J Am Coll Cardiol. 2020;76:2368-2378.
    1. Izmailova ES, Ellis R, Benko C. Remote monitoring in clinical trials during the COVID-19 pandemic. Clin Transl Sci. 2020;13:838-841.
    1. Yang G, Li M, Zhang H, Yang Y. The challenge and management of clinical trials in integrative cancer during the COVID-19 pandemic worldwide. Integr Cancer Ther. 2021;20:1534735421991218.

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