PMID- 30782213 OWN - NLM STAT- MEDLINE DCOM- 20190613 LR - 20220408 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 20 IP - 1 DP - 2019 Feb 19 TI - Efficacy and safety of levothyroxine (L-T4) replacement on the exercise capability in chronic systolic heart failure patients with subclinical hypothyroidism: Study protocol for a multi-center, open label, randomized, parallel group trial (ThyroHeart-CHF). PG - 143 LID - 10.1186/s13063-019-3219-5 [doi] LID - 143 AB - BACKGROUND: Subclinical hypothyroidism is a common condition in patients with heart failure and is defined as elevated serum thyroid hormone (TSH) with normal circulating free thyroxine (FT4). Evidence on the effect of thyroid hormone treatment is lacking. We designed a randomized controlled trial to compare the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. METHODS/DESIGN: Eligible participants were identified from the cardiology units of five study centers based on the following criteria: 18 years or older, systolic heart failure with NewYork Heart Association (NYHA) class II-III, left ventricular ejection fraction 4.78muIU/ml, < 10 muIU/ml + FT4 level within reference range). Eligible patients will be randomly assigned in a 1:1 manner to receive thyroxine replacement therapy plus standard chronic heart failure (CHF) treatment or only standard CHF therapy. Levothyroxine will be administered at an initial dose of 12.5 mug once daily and will be titrated until TSH is within the normal range. The primary endpoints include the difference in distance of the six-minute walk test between 24 weeks and baseline. The secondary endpoints include differences in plasma NT-proBNP levels and serum lipid profiles, changes in the NYHA classification, cardiovascular death, re-hospitalization, differences in echocardiographic and cardiac magnetic resonance imaging measures, and Minnesota Living With Heart Failure Questionnaire (MLHFQ) results between 24 weeks and baseline. DISCUSSION: ThyroHeart-CHF is designed as a prospective, multi-center, randomized, controlled clinical trial to study the efficacy and safety of thyroid hormone supplementation in patients with chronic heart failure complicated with subclinical hypothyroidism. The study findings will have significant implications for discovering the new therapeutic targets and methods of heart failure. TRAIL REGISTRATION: ClinicalTrials.gov, NCT03096613 . Registered on 30 March 2017. FAU - Zhang, Xuan AU - Zhang X AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Wang, Wen-Yao AU - Wang WY AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Zhang, Kuo AU - Zhang K AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Tian, Jian AU - Tian J AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Zheng, Ji-Lin AU - Zheng JL AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Chen, Jing AU - Chen J AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - An, Shi-Min AU - An SM AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Wang, Si-Yuan AU - Wang SY AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Liu, Yu-Peng AU - Liu YP AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Zhao, Yan AU - Zhao Y AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Wang, Jing-Jia AU - Wang JJ AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Yang, Min AU - Yang M AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. FAU - Tang, Yi-da AU - Tang YD AUID- ORCID: 0000-0002-9712-803X AD - Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. tangyida@fuwaihospital.org. LA - eng SI - ClinicalTrials.gov/NCT03096613 GR - Z151100004015175/Beijing Municipal Commission of Science and Technology/ GR - Z181100006318005/Beijing Municipal Commission of Science and Technology/ GR - 2016-12M-1-009/CAMS Innovation Fund for Medical Sciences/ PT - Clinical Trial Protocol PT - Journal Article DEP - 20190219 PL - England TA - Trials JT - Trials JID - 101263253 RN - Q51BO43MG4 (Thyroxine) SB - IM MH - Asymptomatic Diseases MH - China MH - Chronic Disease MH - Exercise Tolerance/*drug effects MH - Heart Failure, Systolic/complications/diagnosis/*drug therapy/physiopathology MH - Hormone Replacement Therapy/adverse effects/*methods MH - Humans MH - Hypothyroidism/complications/diagnosis/*drug therapy/physiopathology MH - Multicenter Studies as Topic MH - Prospective Studies MH - Randomized Controlled Trials as Topic MH - Thyroxine/adverse effects/*therapeutic use MH - Time Factors MH - Treatment Outcome MH - Ventricular Function, Left/drug effects MH - Walk Test PMC - PMC6381733 COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the institutional review board central committee at Fuwai Hospital, NCCD of China, and complies with the Declaration of Helsinki. Informed consent will be obtained from each participating patient. After the subjects have signed informed consent, patient data will be populated per the protocol. IRB number(Approval No.) of Fu Wai hospital is 2016-798, IRB number of The Second hospital of Tianjin Medical University is KY2017K037, IRB number of The First Hospital of Hebe Medical University is 2,017,001, IRB number of Henan Provincial People's Hospital is 2017-12, IRB number of Luhe hospital is 2017-LHYW-01. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/02/21 06:00 MHDA- 2019/06/14 06:00 PMCR- 2019/02/19 CRDT- 2019/02/21 06:00 PHST- 2018/06/07 00:00 [received] PHST- 2019/01/22 00:00 [accepted] PHST- 2019/02/21 06:00 [entrez] PHST- 2019/02/21 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2019/02/19 00:00 [pmc-release] AID - 10.1186/s13063-019-3219-5 [pii] AID - 3219 [pii] AID - 10.1186/s13063-019-3219-5 [doi] PST - epublish SO - Trials. 2019 Feb 19;20(1):143. doi: 10.1186/s13063-019-3219-5.