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Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study.

Abstract

AIMS

Despite recent advances in the treatment of chronic heart failure (HF), mortality and hospitalizations still remain high. Additional therapies to improve mortality and morbidity are urgently needed. The efficacy of cardiac glycosides - although regularly used for HF treatment - remains unclear. DIGIT-HF was designed to demonstrate that digitoxin on top of standard of care treatment improves mortality and morbidity in patients with HF and a reduced ejection fraction (HFrEF).

METHODS

Patients with chronic HF, New York Heart Association (NYHA) functional class III-IV and left ventricular ejection fraction (LVEF) ≤ 40%, or patients in NYHA functional class II and LVEF ≤ 30% are randomized 1:1 in a double-blind fashion to treatment with digitoxin (target serum concentration 8-18 ng/mL) or matching placebo. Randomization is stratified by centre, sex, NYHA functional class (II, III, or IV), atrial fibrillation, and treatment with cardiac glycosides at baseline. A total of 2190 eligible patients will be included in this clinical trial (1095 per group). All patients receive standard of care treatment recommended by expert guidelines upon discretion of the treating physician. The primary outcome is a composite of all-cause mortality or hospital admission for worsening HF (whatever occurs first). Key secondary endpoints are all-cause mortality, hospital admission for worsening HF, and recurrent hospital admission for worsening HF.

CONCLUSION

The DIGIT-HF trial will provide important evidence, whether the cardiac glycoside digitoxin reduces the risk for all-cause mortality and/or hospital admission for worsening HF in patients with advanced chronic HFrEF on top of standard of care treatment.

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  • Publisher Full Text
  • Authors+Show Affiliations

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Department of Biostatistics, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology, Cardiovascular Center, Clinical Center Nuernberg, Paracelsus Medical University, Nuernberg, Germany.

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    Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.

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    Department of Cardiology and Intensive Care Medicine, Elbe Clinic Stade, Stade, Germany.

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    Department of Cardiology, Kerckhoff Heart, Rheuma and Thoracic Center, Bad Nauheim, Germany.

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    Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany.

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    Department of Electrophysiology, Heart Center, University of Technology Dresden, Dresden, Germany.

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    Department of Biostatistics, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Hannover Clinical Trial Centre, Hannover, Germany.

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    Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

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    Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany.

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    Department of Internal Medicine III, University Hospital of the Saarland, Homburg, Germany.

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    Department of Biostatistics, Hannover Medical School, Hannover, Germany.

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    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

    Source

    European journal of heart failure 21:5 2019 May pg 676-684

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30892806

    Citation

    Bavendiek, Udo, et al. "Rationale and Design of the DIGIT-HF Trial (DIGitoxin to Improve ouTcomes in Patients With Advanced Chronic Heart Failure): a Randomized, Double-blind, Placebo-controlled Study." European Journal of Heart Failure, vol. 21, no. 5, 2019, pp. 676-684.
    Bavendiek U, Berliner D, Dávila LA, et al. Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study. Eur J Heart Fail. 2019;21(5):676-684.
    Bavendiek, U., Berliner, D., Dávila, L. A., Schwab, J., Maier, L., Philipp, S. A., ... Bauersachs, J. (2019). Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study. European Journal of Heart Failure, 21(5), pp. 676-684. doi:10.1002/ejhf.1452.
    Bavendiek U, et al. Rationale and Design of the DIGIT-HF Trial (DIGitoxin to Improve ouTcomes in Patients With Advanced Chronic Heart Failure): a Randomized, Double-blind, Placebo-controlled Study. Eur J Heart Fail. 2019;21(5):676-684. PubMed PMID: 30892806.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study. AU - Bavendiek,Udo, AU - Berliner,Dominik, AU - Dávila,Lukas Aguirre, AU - Schwab,Johannes, AU - Maier,Lars, AU - Philipp,Sebastian A, AU - Rieth,Andreas, AU - Westenfeld,Ralf, AU - Piorkowski,Christopher, AU - Weber,Kristina, AU - Hänselmann,Anja, AU - Oldhafer,Maximiliane, AU - Schallhorn,Sven, AU - von der Leyen,Heiko, AU - Schröder,Christoph, AU - Veltmann,Christian, AU - Störk,Stefan, AU - Böhm,Michael, AU - Koch,Armin, AU - Bauersachs,Johann, AU - ,, Y1 - 2019/03/20/ PY - 2018/11/19/received PY - 2019/01/31/revised PY - 2019/02/06/accepted PY - 2019/3/21/pubmed PY - 2019/3/21/medline PY - 2019/3/21/entrez KW - Cardiac glycosides KW - Clinical trial KW - Digitalis KW - Digitoxin KW - Heart failure SP - 676 EP - 684 JF - European journal of heart failure JO - Eur. J. Heart Fail. VL - 21 IS - 5 N2 - AIMS: Despite recent advances in the treatment of chronic heart failure (HF), mortality and hospitalizations still remain high. Additional therapies to improve mortality and morbidity are urgently needed. The efficacy of cardiac glycosides - although regularly used for HF treatment - remains unclear. DIGIT-HF was designed to demonstrate that digitoxin on top of standard of care treatment improves mortality and morbidity in patients with HF and a reduced ejection fraction (HFrEF). METHODS: Patients with chronic HF, New York Heart Association (NYHA) functional class III-IV and left ventricular ejection fraction (LVEF) ≤ 40%, or patients in NYHA functional class II and LVEF ≤ 30% are randomized 1:1 in a double-blind fashion to treatment with digitoxin (target serum concentration 8-18 ng/mL) or matching placebo. Randomization is stratified by centre, sex, NYHA functional class (II, III, or IV), atrial fibrillation, and treatment with cardiac glycosides at baseline. A total of 2190 eligible patients will be included in this clinical trial (1095 per group). All patients receive standard of care treatment recommended by expert guidelines upon discretion of the treating physician. The primary outcome is a composite of all-cause mortality or hospital admission for worsening HF (whatever occurs first). Key secondary endpoints are all-cause mortality, hospital admission for worsening HF, and recurrent hospital admission for worsening HF. CONCLUSION: The DIGIT-HF trial will provide important evidence, whether the cardiac glycoside digitoxin reduces the risk for all-cause mortality and/or hospital admission for worsening HF in patients with advanced chronic HFrEF on top of standard of care treatment. SN - 1879-0844 UR - https://www.unboundmedicine.com/medline/citation/30892806/Rationale_and_design_of_the_DIGIT-HF_trial_(DIGitoxin_to_Improve_ouTcomes_in_patients_with_advanced_chronic_Heart_Failure):_a_randomized,_double-blind,_placebo-controlled_study L2 - https://doi.org/10.1002/ejhf.1452 DB - PRIME DP - Unbound Medicine ER -