Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
COMPLETED
Clinical Phase
PHASE3
Study Classification
INTERVENTIONAL
Study Start Date
1990-06-30
Study Completion Date
1998-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
To determine if digitalis had a beneficial, harmful, or no effect on total mortality in patients with clinical heart failure and sinus rhythm.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacy Study of Digoxin & Ivabradine to Treat Heart Failure
NCT01699776
Cardiac Failure
COMPLETED
PHASE4
Digoxin Evaluation in Chronic Heart Failure: Investigational Study In Outpatients in the Netherlands
NCT03783429
Heart Failure
ACTIVE_NOT_RECRUITING
PHASE4
Digoxin Versus Ivabradine in Heart Failure With Reduced Ejection Fraction
NCT02046044
Heart Failure
UNKNOWN
PHASE4
A Drug Interaction Study of Albiglutide and Digoxin
NCT01147718
Diabetes Mellitus, Type 2
COMPLETED
PHASE1
Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care
NCT01005602
Heart Failure
COMPLETED
PHASE4
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
BACKGROUND:
Despite widespread use of digitalis and its availability for nearly two centuries, uncertainty surrounded the appropriateness of its role and value in treating congestive heart failure patients in sinus rhythm. The study was a multicenter collaborative effort with the Department of Veteran Affairs Cooperative Studies Program which provided support for a data coordinating center and a pharmacy coordinating center.
DESIGN NARRATIVE:
Randomized, double-blind, simple, multicenter, international trial with 186 centers in the United States and 116 in Canada. In the main trial, patients with left ventricular ejection fractions of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and ACE inhibitors. In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo. Patients were recruited over a three-year period at the 302 centers and followed for a minimum of two years. Patient enrollment began in February 1991 and ended in September 1993. Follow-up ended in December 1995. The main results paper was published in 1997.
Three substudies were conducted. The quality of life/6-minute walk test substudy determined the effect of treatment on a patient's well-being, daily activities, and functional status. The Holter/signal averaging electrocardiogram substudy examined the pathophysiology of sudden cardiac death. The neurohormonal substudy determined whether long-term administration of digoxin attenuated the neuroendocrine response in patients with heart failure.
The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).
Despite widespread use of digitalis and its availability for nearly two centuries, uncertainty surrounded the appropriateness of its role and value in treating congestive heart failure patients in sinus rhythm. The study was a multicenter collaborative effort with the Department of Veteran Affairs Cooperative Studies Program which provided support for a data coordinating center and a pharmacy coordinating center.
DESIGN NARRATIVE:
Randomized, double-blind, simple, multicenter, international trial with 186 centers in the United States and 116 in Canada. In the main trial, patients with left ventricular ejection fractions of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and ACE inhibitors. In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo. Patients were recruited over a three-year period at the 302 centers and followed for a minimum of two years. Patient enrollment began in February 1991 and ended in September 1993. Follow-up ended in December 1995. The main results paper was published in 1997.
Three substudies were conducted. The quality of life/6-minute walk test substudy determined the effect of treatment on a patient's well-being, daily activities, and functional status. The Holter/signal averaging electrocardiogram substudy examined the pathophysiology of sudden cardiac death. The neurohormonal substudy determined whether long-term administration of digoxin attenuated the neuroendocrine response in patients with heart failure.
The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Arrhythmia
Cardiovascular Diseases
Heart Diseases
Heart Failure, Congestive
Sinus Arrhythmia
Heart Failure
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
digitalis
Intervention Type
DRUG
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Men and women with clinical heart failure, sinus rhythm, and an ejection fraction less than or equal to 45 percent.
Minimum Eligible Age
21 Years
Maximum Eligible Age
75 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Sponsor Role
lead
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
No Collins
Role:
US Department of Veterans Affairs
No Fye
Role:
US Department of Veterans Affairs
References
Explore related publications, articles, or registry entries linked to this study.
Collins JF, Cline DR, Garg R, and the DIG Study Group . Protecting patient's rights: the DIG study experience. Controlled Clin Trials 1994;15:135S.
Reference Type
BACKGROUND
Egan D, Garg R, Horney A for the Digitalis Investigation Group. Differences in patient populations between cardiovascular and noncardiovascular specialties: the DIG experience. Controlled Clin Trials 15:128S, 1994.
Reference Type
BACKGROUND
Garg R, Yusuf S, Gorlin R on behalf of the Digitalis Investigation Group. Inclusion of patients only with low ejection fraction in heart failure trial biases the population against women and the elderly. J Am Coll Cardiol Feb, 429A, 1994.
Reference Type
BACKGROUND
Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997 Feb 20;336(8):525-33. doi: 10.1056/NEJM199702203360801.
Reference Type
BACKGROUND
Packer M. End of the oldest controversy in medicine. Are we ready to conclude the debate on digitalis? N Engl J Med. 1997 Feb 20;336(8):575-6. doi: 10.1056/NEJM199702203360809. No abstract available.
Reference Type
BACKGROUND
Gheorghiade M, Pitt B. Digitalis Investigation Group (DIG) trial: a stimulus for further research. Am Heart J. 1997 Jul;134(1):3-12. doi: 10.1016/s0002-8703(97)70100-5. No abstract available.
Reference Type
BACKGROUND
Philbin EF, Garg R, Danisa K, Denny M, Gosselin G, Hassapoyannes C, Horney A, Johnstone DE, Lang RM, Ramanathan K, Safford RE, Sarma RJ, Weiss R, Williford WO, Fleg JL. The relationship between cardiothoracic ratio and left ventricular ejection fraction in congestive heart failure. Digitalis Investigation Group. Arch Intern Med. 1998 Mar 9;158(5):501-6. doi: 10.1001/archinte.158.5.501.
Reference Type
BACKGROUND
Hobbs RE. Digoxin's effect on mortality and hospitalization in heart failure: implications of the DIG study. Digitalis Investigation Group. Cleve Clin J Med. 1997 May;64(5):234-7. doi: 10.3949/ccjm.64.5.234. No abstract available.
Reference Type
BACKGROUND
Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: a large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure. Control Clin Trials. 1996 Feb;17(1):77-97. doi: 10.1016/0197-2456(95)00065-8.
Reference Type
BACKGROUND
Rich MW, McSherry F, Williford WO, Yusuf S; Digitalis Investigation Group. Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol. 2001 Sep;38(3):806-13. doi: 10.1016/s0735-1097(01)01442-5.
Reference Type
BACKGROUND
Philbin EF, Hunsberger S, Garg R, Lader E, Thadani U, McSherry F, Silver MA; Digitalis Investigation Group. Usefulness of clinical information to distinguish patients with normal from those with low ejection fractions in heart failure. Am J Cardiol. 2002 May 15;89(10):1218-21. doi: 10.1016/s0002-9149(02)02311-1. No abstract available.
Reference Type
BACKGROUND
Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med. 2002 Oct 31;347(18):1403-11. doi: 10.1056/NEJMoa021266.
Reference Type
BACKGROUND
Fye CL, Gagne WH, Raisch DW, Jones MS, Sather MR, Buchanan SL, Chacon FR, Garg R, Yusuf S, Williford WO; DIG Investigators. The role of the pharmacy coordinating center in the DIG trial. Control Clin Trials. 2003 Dec;24(6 Suppl):289S-297S. doi: 10.1016/s0197-2456(03)00102-8.
Reference Type
BACKGROUND
Williford WO, Collins JF, Horney A, Kirk G, McSherry F, Spence E, Stinnett S, Howell CL, Garg R, Egan D, Yusuf S; DIG Investigators. The role of the data coordinating center in the DIG trial. Control Clin Trials. 2003 Dec;24(6 Suppl):277S-288S. doi: 10.1016/s0197-2456(03)00103-x.
Reference Type
BACKGROUND
Collins JF, Egan D, Yusuf S, Garg R, Williford WO, Geller N; DIG Investigators. Overview of the DIG trial. Control Clin Trials. 2003 Dec;24(6 Suppl):269S-276S. doi: 10.1016/s0197-2456(03)00104-1.
Reference Type
BACKGROUND
Collins JF, Howell CL, Horney RA; Digitalis Investigation Group Investigators. Determination of vital status at the end of the DIG trial. Control Clin Trials. 2003 Dec;24(6):726-30. doi: 10.1016/j.cct.2003.08.011.
Reference Type
BACKGROUND
Egan D, Geller N, Yusuf S, Garg R, Collins JF, Mathew J, Philbin E; DIG Investigators. Lessons learned from the DIG trial. Control Clin Trials. 2003 Dec;24(6 Suppl):316S-326S. doi: 10.1016/s0197-2456(03)00099-0.
Reference Type
BACKGROUND
Collins JF, Martin S, Kent E, Liuni C, Garg R, Egan D; DIG Investigators. The use of regional coordinating centers in large clinical trials: the DIG trial. Control Clin Trials. 2003 Dec;24(6 Suppl):298S-305S. doi: 10.1016/s0197-2456(03)00101-6.
Reference Type
BACKGROUND
Jones RC, Francis GS, Lauer MS. Predictors of mortality in patients with heart failure and preserved systolic function in the Digitalis Investigation Group trial. J Am Coll Cardiol. 2004 Sep 1;44(5):1025-9. doi: 10.1016/j.jacc.2004.05.077.
Reference Type
BACKGROUND
Adams KF Jr, Patterson JH, Gattis WA, O'Connor CM, Lee CR, Schwartz TA, Gheorghiade M. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol. 2005 Aug 2;46(3):497-504. doi: 10.1016/j.jacc.2005.02.091.
Reference Type
BACKGROUND
Mathew J, Wittes J, McSherry F, Williford W, Garg R, Probstfield J, Yusuf S; Digitalis Investigation Group. Racial differences in outcome and treatment effect in congestive heart failure. Am Heart J. 2005 Nov;150(5):968-76. doi: 10.1016/j.ahj.2005.03.060.
Reference Type
BACKGROUND
Study Documents
Access uploaded study-related documents such as protocols, statistical analysis plans, or lay summaries.
Document Type: Individual Participant Data Set
NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
View DocumentDocument Type: Study Protocol
View DocumentDocument Type: Study Forms
View DocumentOther Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
65
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease
NCT03877965
COMPLETED
Effect of Dapagliflozin on VT in Patients With Heart Failure.
NCT05550441
UNKNOWN
PHASE4
Efficacy and Safety of Dapagliflozin in Preventing Atrial Fibrillation Recurrence After Catheter Ablation
NCT06740786
NOT_YET_RECRUITING
NA
A Study of the Efficacy and Safety of Danicamtiv in Participants With Symptomatic Genetic and Familial Dilated Cardiomyopathy
NCT07210723
RECRUITING
PHASE2/PHASE3
Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
NCT01396395
COMPLETED
PHASE4
Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients
NCT03271879
UNKNOWN
PHASE4
Efficacy of Ivabradine in Patient With Both Persistent Atrial Fibrillation and Heart Failure With Reduce Ejection Fraction
NCT04308031
UNKNOWN
PHASE3
Sodium-glucose Co-transporter 2 Inhibitors Effects in Failing Heart Patients
NCT03977116
COMPLETED
PHASE4
Study to Evaluate the Effect of Solifenacin and Mirabegron on the Digoxin Concentrations in Blood in Healthy Subjects
NCT02127034
COMPLETED
PHASE1
Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients
NCT02167165
COMPLETED
Ertugliflozin in Chronic Heart Failure
NCT04438213
RECRUITING
PHASE2
Digoxin Short Term Treatment Assessment Randomized Trial in AHF
NCT02544815
RECRUITING
PHASE3
Safety and Efficacy Study of an A1-Adenosine Receptor Agonist to Slow Heart Rate in Atrial Fibrillation
NCT00040001
COMPLETED
PHASE2
A Study of Evacetrapib and Digoxin in Healthy Participants
NCT01897493
COMPLETED
PHASE1
Digoxin Withdrawal in Stable Heart Failure
NCT01398371
COMPLETED
NA
Regulation of Immunological Cytokines by Qiliqiangxin Capsule in Dilated Cardiomyopathy Patients
NCT02283450
COMPLETED
Study of Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy
NCT04164732
COMPLETED
PHASE2
A Trial to Evaluate the Effect of Delgocitinib on the Heart Rhythm of Healthy People
NCT05050279
COMPLETED
EARLY_PHASE1
An Exploratory Safety and Efficacy Clinical Study of CARDIX-101 for the Treatment of Chronic Bradycardia
NCT05117346
COMPLETED
PHASE1/PHASE2
Impact of Sodium-glucose Cotransporter 2 Inhibitors on Post-operative Atrial Fibrillation in Cardiothoracic Surgery
NCT06251453
UNKNOWN
Effects of Docosahexaenoic Acid (DHA) on Heart Rate Variability in Elderly Patients
NCT00749307
COMPLETED
PHASE2/PHASE3
Dapagliflozin on Outcomes of Rhythm Control Strategy (Pharmacological ± Interventional) in Patient with Atrial Fibrillation
NCT06759909
NOT_YET_RECRUITING
PHASE1
PK/PD of Digoxin in Infants With SVHD
NCT06613477
RECRUITING
PHASE1/PHASE2
Pharmacokinetic and Pharmacodynamic Interaction Study of Digoxin and Hawthorn
NCT00006330
COMPLETED
NA
Digoxin Versus Ivabradine in Heart Failure With Preserved Systolic Function
NCT01796093
COMPLETED