PMID- 30892806
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20240320
IS  - 1879-0844 (Electronic)
IS  - 1388-9842 (Print)
IS  - 1388-9842 (Linking)
VI  - 21
IP  - 5
DP  - 2019 May
TI  - 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.
PG  - 676-684
LID - 10.1002/ejhf.1452 [doi]
AB  - 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.
CI  - (c) 2019 The Authors. European Journal of Heart Failure published by John Wiley & 
      Sons Ltd on behalf of European Society of Cardiology.
FAU - Bavendiek, Udo
AU  - Bavendiek U
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - Berliner, Dominik
AU  - Berliner D
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - Davila, Lukas Aguirre
AU  - Davila LA
AD  - Department of Biostatistics, Hannover Medical School, Hannover, Germany.
FAU - Schwab, Johannes
AU  - Schwab J
AD  - Department of Cardiology, Cardiovascular Center, Clinical Center Nuernberg, 
      Paracelsus Medical University, Nuernberg, Germany.
FAU - Maier, Lars
AU  - Maier L
AD  - Department of Internal Medicine II, University Medical Center Regensburg, 
      Regensburg, Germany.
FAU - Philipp, Sebastian A
AU  - Philipp SA
AD  - Department of Cardiology and Intensive Care Medicine, Elbe Clinic Stade, Stade, 
      Germany.
FAU - Rieth, Andreas
AU  - Rieth A
AD  - Department of Cardiology, Kerckhoff Heart, Rheuma and Thoracic Center, Bad 
      Nauheim, Germany.
FAU - Westenfeld, Ralf
AU  - Westenfeld R
AD  - Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, 
      University Duesseldorf, Duesseldorf, Germany.
FAU - Piorkowski, Christopher
AU  - Piorkowski C
AD  - Department of Electrophysiology, Heart Center, University of Technology Dresden, 
      Dresden, Germany.
FAU - Weber, Kristina
AU  - Weber K
AD  - Department of Biostatistics, Hannover Medical School, Hannover, Germany.
FAU - Hanselmann, Anja
AU  - Hanselmann A
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - Oldhafer, Maximiliane
AU  - Oldhafer M
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - Schallhorn, Sven
AU  - Schallhorn S
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - von der Leyen, Heiko
AU  - von der Leyen H
AD  - Hannover Clinical Trial Centre, Hannover, Germany.
FAU - Schroder, Christoph
AU  - Schroder C
AD  - Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
FAU - Veltmann, Christian
AU  - Veltmann C
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
FAU - Stork, Stefan
AU  - Stork S
AD  - Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, 
      Germany.
FAU - Bohm, Michael
AU  - Bohm M
AD  - Department of Internal Medicine III, University Hospital of the Saarland, 
      Homburg, Germany.
FAU - Koch, Armin
AU  - Koch A
AD  - Department of Biostatistics, Hannover Medical School, Hannover, Germany.
FAU - Bauersachs, Johann
AU  - Bauersachs J
AD  - Department of Cardiology and Angiology, Hannover Medical School, Hannover, 
      Germany.
CN  - DIGIT-HF Investigators and Committees (see Appendix)
LA  - eng
PT  - Clinical Trial Protocol
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190320
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Cardiotonic Agents)
RN  - E90NZP2L9U (Digitoxin)
SB  - IM
MH  - Humans
MH  - *Cardiotonic Agents/therapeutic use
MH  - Cause of Death
MH  - Chronic Disease
MH  - *Digitoxin/therapeutic use
MH  - Double-Blind Method
MH  - *Heart Failure/drug therapy
MH  - *Hospitalization/statistics & numerical data
MH  - *Mortality
MH  - Clinical Trials, Phase IV as Topic
MH  - Pragmatic Clinical Trials as Topic
MH  - Multicenter Studies as Topic
MH  - Randomized Controlled Trials as Topic
PMC - PMC6607489
OTO - NOTNLM
OT  - Cardiac glycosides
OT  - Clinical trial
OT  - Digitalis
OT  - Digitoxin
OT  - Heart failure
FIR - Bavendiek, Udo
IR  - Bavendiek U
FIR - Bauersachs, Johann
IR  - Bauersachs J
FIR - Koch, Armin
IR  - Koch A
FIR - von der Leyen, Heiko
IR  - von der Leyen H
FIR - Veltmann, Christian
IR  - Veltmann C
FIR - Bohm, Michael
IR  - Bohm M
FIR - Stork, Stefan
IR  - Stork S
FIR - Tebbe, Ulrich
IR  - Tebbe U
FIR - von Haehling, Stephan
IR  - von Haehling S
FIR - Haass, Markus
IR  - Haass M
FIR - Anker, Stefan
IR  - Anker S
FIR - Mohacsi, Paul
IR  - Mohacsi P
FIR - Polzl, Gerhard
IR  - Polzl G
FIR - Trampisch, Helmut
IR  - Trampisch H
FIR - Davila, Lukas Aguirre
IR  - Davila LA
FIR - Weber, Kristina
IR  - Weber K
FIR - Zimmermann, Silke
IR  - Zimmermann S
FIR - Neuhaus, Barbara
IR  - Neuhaus B
EDAT- 2019/03/21 06:00
MHDA- 2020/09/10 06:00
PMCR- 2019/03/20
CRDT- 2019/03/21 06:00
PHST- 2018/11/19 00:00 [received]
PHST- 2019/01/31 00:00 [revised]
PHST- 2019/02/06 00:00 [accepted]
PHST- 2019/03/21 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
PHST- 2019/03/21 06:00 [entrez]
PHST- 2019/03/20 00:00 [pmc-release]
AID - EJHF1452 [pii]
AID - 10.1002/ejhf.1452 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2019 May;21(5):676-684. doi: 10.1002/ejhf.1452. Epub 2019 Mar 
      20.