Thiamine versus placebo in older heart failure patients: study protocol for a randomized controlled crossover feasibility trial (THIAMINE-HF)

Eric Kai Chung Wong, Justin Yusen Lee, Darryl P Leong, Lawrence Mbuagbaw, Haroon Yousuf, Sabina Keen, Sharon E Straus, Christopher J Patterson, Catherine Demers, Eric Kai Chung Wong, Justin Yusen Lee, Darryl P Leong, Lawrence Mbuagbaw, Haroon Yousuf, Sabina Keen, Sharon E Straus, Christopher J Patterson, Catherine Demers

Abstract

Background: Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency occurs in 33% of patients with HF. However, the effectiveness of thiamine supplementation in HF is not known.

Methods: In a placebo-controlled randomized two-period crossover feasibility trial, patients age ≥ 60 years with HF and reduced ejection fraction (HFrEF, EF ≤ 45%) will be randomized to thiamine 500 mg oral capsule once daily or placebo for 3 months, then crossed over to the other intervention after a 6-week washout period. The primary outcome is recruitment rate. Secondary outcomes include feasibility and clinical measures. Feasibility outcomes include refusal rate, retention rate, and compliance rate. Secondary clinical outcomes include left ventricular ejection fraction, peak global longitudinal strain measured by echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life score, and clinical outcomes (all-cause mortality, HF hospitalizations, and HF emergency room visits).

Discussion: Thiamine is potentially a safe and low-cost treatment for older patients with HFrEF. Results from this study will inform the feasibility of a large clinical trial with clinical endpoints. The findings will be published in a peer review journal and presented at a relevant conference. This study has received full approval from the Hamilton Integrated Research Ethics Board (18-4537) and Health Canada (210603). This trial is funded by the Hamilton Health Sciences New Investigator Grant (15-387) and the McMaster/St. Peter's Hospital Chair of Aging.

Trial registration: NCT03228030 (ClinicalTrials.gov), registered July 24, 2017.

Keywords: Crossover; Elderly; Heart failure; Placebo; Randomized controlled trial; Thiamine.

Conflict of interest statement

The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow and assessment intervals

References

    1. Ross H, Howlett J, Arnold JMO, Liu P, O’Neill BJ, Brophy JM, et al. Treating the right patient at the right time: access to heart failure care. Can J Cardiol. 2006;22:749–754. doi: 10.1016/S0828-282X(06)70290-2.
    1. Ko DT, Alter DA, Austin PC, You JJ, Lee DS, Qiu F, et al. Life expectancy after an index hospitalization for patients with heart failure: a population-based study. Am Heart J. 2008;155:324–331. doi: 10.1016/j.ahj.2007.08.036.
    1. Johansen H, Strauss B, Arnold JMO, Moe G, Liu P. On the rise: the current and projected future burden of congestive heart failure hospitalization in Canada. Can J Cardiol. 2003;19:430–435.
    1. Cook C, Cole G, Asaria P, Jabbour R, Francis DP. The annual global economic burden of heart failure. Int J Cardiol. 2014;171:368–376. doi: 10.1016/j.ijcard.2013.12.028.
    1. Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007;356:1140–1151. doi: 10.1056/NEJMra063052.
    1. Gangolf M, Czerniecki J, Radermecker M, Detry O, Nisolle M, Jouan C, et al. Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells. PLoS One. 2010;5:e13616. doi: 10.1371/journal.pone.0013616.
    1. Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol Suppl. 2000;35:2–7. doi: 10.1093/alcalc/35.Supplement_1.2.
    1. Baines M, Davies G. The evaluation of erythrocyte thiamin diphosphate as an indicator of thiamin status in man, and its comparison with erythrocyte transketolase activity measurements. Ann Clin Biochem. 1988;25(Pt 6):698–705. doi: 10.1177/000456328802500617.
    1. Hanninen SA, Darling PB, Sole MJ, Barr A, Keith ME. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol. 2006;47:354–361. doi: 10.1016/j.jacc.2005.08.060.
    1. Bello S, Neri M, Riezzo I, Othman MS, Turillazzi E, Fineschi V. Cardiac beriberi: morphological findings in two fatal cases. Diagn Pathol. 2011;6:8. doi: 10.1186/1746-1596-6-8.
    1. Suter PM, Haller J, Hany A, Vetter W. Diuretic use: a risk for subclinical thiamine deficiency in elderly patients. J Nutr Health Aging. 2000;4:69–71.
    1. Sica Domenic A. Loop Diuretic Therapy, Thiamine Balance, and Heart Failure. Congestive Heart Failure. 2007;13(4):244–247. doi: 10.1111/j.1527-5299.2007.06260.x.
    1. Zenuk C, Healey J, Donnelly J, Vaillancourt R, Almalki Y, Smith S. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol. 2003;10:184–188.
    1. Lubetsky A, Winaver J, Seligmann H, Olchovsky D, Almog S, Halkin H, et al. Urinary thiamine excretion in the rat: effects of furosemide, other diuretics, and volume load. J Lab Clin Med. 1999;134:232–237. doi: 10.1016/S0022-2143(99)90202-0.
    1. Rieck J, Halkin H, Almog S, Seligman H, Lubetsky A, Olchovsky D, et al. Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers. J Lab Clin Med. 1999;134:238–243. doi: 10.1016/S0022-2143(99)90203-2.
    1. Wilkinson TJ, Hanger HC, George PM, Sainsbury R. Is thiamine deficiency in elderly people related to age or co-morbidity? Age Ageing. 2000;29:111–116. doi: 10.1093/ageing/29.2.111.
    1. Levy WC, Soine LA, Huth MM, Fishbein DP. Thiamine deficiency in congestive heart failure. Am J Med. 1992;93:705–706. doi: 10.1016/0002-9343(92)90212-T.
    1. Tuppin P, Cuerq A, de Peretti C, Fagot-Campagna A, Danchin N, Juillière Y, et al. Two-year outcome of patients after a first hospitalization for heart failure: a national observational study. Arch Cardiovasc Dis. 2014;107:158–168. doi: 10.1016/j.acvd.2014.01.012.
    1. Dharmarajan K, Hsieh AF, Kulkarni VT, Lin Z, Ross JS, Horwitz LI, et al. Trajectories of risk after hospitalization for heart failure, acute myocardial infarction, or pneumonia: retrospective cohort study. BMJ. 2015;h411:350.
    1. Butt P, Beirness D, Gliksman L, Paradis C, Stockwell T. Alcohol and health in Canada: a summary of evidence and guidelines for low-risk drinking. Ottawa: Canadian Centre on Substance Abuse; 2011.
    1. Stampehl MR, Mann DL, Nguyen JS, Cota F, Colmenares C, Dokainish H. Speckle strain echocardiography predicts outcome in patients with heart failure with both depressed and preserved left ventricular ejection fraction. Echocardiography. 2014;24:1639–1641. doi: 10.1111/echo.12613.
    1. Leto L, Feola M. Cognitive impairment in heart failure patients. J Geriatr Cardiol. 2014;11:316–328. doi: 10.11909/j.issn.1671-5411.2014.04.007.
    1. Sibbald B, Roberts C. Understanding controlled trials. Crossover trials. BMJ. 1998;316:1719. doi: 10.1136/BMJ.316.7146.1719.
    1. Ariaey-Nejad MR, Balaghi M, Baker EM, Sauberlich HE. Thiamin metabolism in man. Am J Clin Nutr. 1970;23:764–778. doi: 10.1093/ajcn/23.6.764.
    1. RD W. Induced thiamine (vitamin B1) deficiency in man. Arch Intern Med. 1943;71:38. doi: 10.1001/archinte.1943.00210010044003.
    1. RD W. Observations on induced thiamine (vitamin B1) deficiency in man. Arch Intern Med. 1940;66:785. doi: 10.1001/archinte.1940.00190160002001.
    1. Schoenenberger AW, Schoenenberger-Berzins R, der Maur CA, Suter PM, Vergopoulos A, Erne P. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. Clin Res Cardiol. 2012;101:159–164. doi: 10.1007/s00392-011-0376-2.
    1. Oremus M, Don-Wauchope A, McKelvie R, Santaguida PL, Hill S, Balion C, et al. BNP and NT-proBNP as prognostic markers in persons with chronic stable heart failure. Heart Fail Rev. 2014;19:471–505. doi: 10.1007/s10741-014-9439-6.
    1. Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City cardiomyopathy questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000;35:1245–1255. doi: 10.1016/S0735-1097(00)00531-3.
    1. Garin O, Herdman M, Vilagut G, Ferrer M, Ribera A, Rajmil L, et al. Assessing health-related quality of life in patients with heart failure: a systematic, standardized comparison of available measures. Heart Fail Rev. 2014;19:359–367. doi: 10.1007/s10741-013-9394-7.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. New York Heart Association . Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9. Boston: Lippincott Williams and Wilkins; 1994.
    1. Willeman T, Casez O, Faure P, Gauchez AS. Evaluation of biotin interference on immunoassays: new data for troponin I, digoxin, NT-pro-BNP, and progesterone. Clin Chem Lab Med. 2017;55:e226–e229. doi: 10.1515/cclm-2016-0980.
    1. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4:287–291. doi: 10.1002/pst.185.
    1. Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008;31:180–191. doi: 10.1002/nur.20247.
    1. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996;276:637–639. doi: 10.1001/jama.1996.03540080059030.
    1. Shimon I, Almog S, Vered Z, Seligmann H, Shefi M, Peleg E, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98:485–490. doi: 10.1016/S0002-9343(99)80349-0.
    1. Dinicolantonio JJ, Lavie CJ, Niazi AK, O’Keefe JH, Hu T. Effects of thiamine on cardiac function in patients with systolic heart failure: systematic review and metaanalysis of randomized, double-blind, placebo-controlled trials. Ochsner J. 2013;13:495–499.

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