DIGIT-HF

Overview
Related items

A multicenter, randomized, double-blind, placebo-controlled study to demonstrate that digitoxin reduces a composite of overall mortality and hospitalization for worsening heart failure in patients with chronic heart failure and reduced ejection fraction

SEEK ID: https://ldh.zks-mhh.imise.uni-leipzig.de/projects/2

Public web page: Not specified

NFDI4Health PALs: No PALs for this Project

Project start date: 23rd Apr 2015

Project end date: 29th Nov 2024

Extended Metadata (Nfdi4Health MDS 3.3)

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Resource classification(*)

Type of the resource : Study

Title(s)/name(s) of the Project

Title/name : A multicenter, randomized, double-blind, placebo-controlled study to demonstrate that digitoxin reduces a composite of overall mortality and hospitalization for worsening heart failure in patients with chronic heart failure and reduced ejection fraction
Language of the title/name : English

Acronym(s) of the Project

Acronym : DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure/ DIGIT-HF
Language of the acronym : English

Description(s) of the Project

Description : A multicenter, randomized, double-blind, placebo-controlled study to demonstrate that digitoxin reduces a composite of overall mortality and hospitalization for worsening heart failure in patients with chronic heart failure and reduced ejection fraction
Language of the description : English

Keyword(s) describing the Project

Keyword(*) : Not specified

Language(s) of the project : English

Contributor(s) of the Project

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Not specified
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Not specified
Details about the contributing person(s)
Contributor type(*) : Principal investigator
Given name(*) : Johann
Family name(s)(*) : Bauersachs
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : bauersachs.johann@mh-hannover.de
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Hannover Medical School, Department of Cardiology & Angiology
Address : Carl-Neuberg-Str. 1 30625 Hannover, Germany
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Not specified
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Not specified
Details about the contributing person(s)
Contributor type(*) : Principal investigator
Given name(*) : Udo
Family name(s)(*) : Bavendiek
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : bavendiek.udo@mh-hannover.de
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Hannover Medical School Department of Cardiology & Angiology
Address : Carl-Neuberg-Str. 1 30625 Hannover, Germany
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Name(*) : Not specified
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Not specified
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Not specified
Details about the contributing person(s)
Contributor type(*) : Sponsor (primary)
Given name(*) : Christoph
Family name(s)(*) : Schindler
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : Schindler.Christoph@mh-hannover.de
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Hannover Medical School (MHH)
Address : Carl-Neuberg-Str. 1 30625 Hannover Germany
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Name(*) : Not specified
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified

Alternative identifiers

Type of the registry(*) : EudraCT
Identifier(*) : 2013-005326-38

Characteristics of the Project

Is it an interventional or non-interventional Project? : Interventional
Specification of the type of the Project
Interventional Project type : Parallel
Non-interventional Project type : []
Primary health condition(s) or disease(s) considered in the Project
Primary health condition or disease name(*) : Chronic heart failure
Terminology/classification(*) : MedDRA
Code of the health condition or disease : 10008908
Groups of diseases or conditions(*)
Which groups of diseases or conditions were the data collected on? : Diseases of the circulatory system (IX)
On which diseases or conditions were the data collected? : []
Collects mortality data? : Not specified
Administrative information about the Project
Status of the ethics committee approval : Request for approval submitted, approval granted
Overall Project status : Completed: Recruitment, data collection, and data quality management completed normally
Participants enrolled by invitation? : Not applicable
Start date : 4 May 2015
End date : 29 November 2024
Mono- or multicentric? : Multicentric
Number of centers : 65
One or more data providers? : Not specified
Number of data providers : Not specified
Primary subject(*) : Person
Eligibility criteria for Project participants
Eligibility criteria: Minimum age
Minimum eligible age(*) : 18
Unit of age(*) : Years
Eligibility criteria: Maximum age
Maximum eligible age(*) : Not specified
Unit of age(*) : Years
Eligible gender : Male, Female, Diverse
Inclusion criteria : 1. Signed written informed consent and willingness to comply with treatment and follow-up 2. Male or female patients age ≥ 18 years at day of inclusion 3. Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial 4. Patients with chronic heart failure NYHA class III-IV and a ventricular ejection fraction of EF ≤ 40%* or patients with heart failure NYHA class II and EF ≤ 30 %* * determined at screening by echocardiography or cardiac magnetic resonance tomography or within 8 weeks prior to study inclusion by left-ventricular angiography, echocardiography, radionuclide ventriculography, cardiac magnetic resonance tomography AND an evidence based heart failure therapy at least for six months upon discretion of the treating physician 5. Women without childbearing potential defined as one or more of following: • Women at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy with or without hysterectomy at the day of inclusion • Women ≥ 50 years of age at the day of inclusion who have been postmenopausal since at least 1 year • Women < 50 years and in postmenopausal state ≥ 1 year with serum FSH > 40 IU/l (proved by a second laboratory assessment after 4 weeks) OR Women of childbearing potential who have a negative hCG pregnancy test and agree to meet one or more of the following criteria from the time of screening/baseline, during the study and for a period of 40 days following the last administration of study medication: • Correct use of reliable contraception methods. This includes hormonal contraceptive (oral contraceptives, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release) or an intrauterine device (IUD/IUS) or a barrier method of contraception such as condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam/gel/film/cream/suppository) • True abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception) • Sexual relationship only with female partners and/or sterile male partners OR Men
Exclusion criteria : 1. Recent (< 2 months ago): myocardial infarction, coronary revascularization, surgery or catheter intervention for valvular heart disease, acute coronary syndrome, stroke or cerebral ischemia, start of heart failure device therapy potentially improving left ventricular ejection fraction or heart failure symptoms (e.g. cardiac resynchronization therapy (CRT), cardiac contractility modulation (CCM), baroreflex-activation therapy (BAT)) 2. Scheduled surgery or catheter intervention for valvular heart disease, scheduled coronary revascularization, scheduled heart failure device therapy potentially improving left ventricular ejection fraction or heart failure symptoms (e.g. cardiac resynchronization therapy (CRT), cardiac contractility modulation (CCM), baroreflex-activation therapy (BAT)) 3. Active myocarditis 4. Complex congenital heart disease; this does not include: mild-moderate valve disease, uncomplicated shunts (isolated patent foramen ovale, small atrial or ventricular septum defects without associated lesions), repaired secundum or sinus venosus atrial septal defects or ventricular septal defects without residua, previously ligated or occluded ductus arteriosus 5. High-urgency listing for heart transplantation or scheduled therapy with left ventricular assist device (LVAD) 6. Heart rate < 60 b.p.m. (except if functional CRT in place) 7. SA-/AV-block > I°, sick sinus syndrome or carotis sinus syndrome (except if pace-maker protected) 8. Proven or suspected accessory, atrio-ventricular pathways (e.g. WPW-syndrome) 9. History of symptomatic or sustained (≥ 30 s) ventricular arrhythmia unless a cardioverter/defibrillator implanted 10. Current ventricular tachycardia or fibrillation (this means patients presenting with a running ventricular tachycardia or fibrillation. If ventricular arrhythmias are terminated and a cardioverter/defibrillator is implanted inclusion is allowed according to point 9.) 11. Hypertrophic obstructive cardiomyopathy (idiopathic subaortic stenosis) 12. Cor pulmonale 13. Constrictive pericarditis 14. Thoracic aortic aneurysm (defined as diameter ≥ 45 mm) 15. Concomitant severe liver and renal disease 16. Persistent hypokalaemia (< 3.2 mM) 17. Hypercalcemia or hypomagnesemia, if clinically suspected and verified by laboratory testing (e. g. hyperparathyroidism, neoplasia induced hypercalcemia, signs of neuromuscular hyperexcitability) 18. Present (within 6 weeks before baseline/day 0 visit) and continuous treatment with Amiodarone (Single or short-term (up to 3 days), not continuous administration of amiodarone immediately before or during study treatment are acceptable) 19. Scheduled direct current cardioversion (DCC) in the next 24 h (e. g. patients not on cardiac glycosides with new onset of atrial fibrillation. Patients already included and on treatment with IMP can continue IMP and study when scheduled for DCC) 20. Presence of both treatment with cardiac glycosides and atrial fibrillation 21. Simultaneous intravenous treatment with calcium salts 22. Evidence of cardiac glycosides intolerance or known hypersensitivity to any component of investigational medicinal products 23. Suspected intoxication with cardiac glycosides 24. Unlikely compliance with protocol requirements 25. Pregnant and lactating women 26. Use of other investigational drugs or devices at the time of enrollment, or within 30 days prior to enrollment or 5 half-lives for investigational drugs, whichever is longer 27. Life expectancy < 12 month (e.g. due to active cancer)
Population of the Project(*)
Coverage : International
Country(ies) : Germany
Region(s) and/or city(ies) : Germany, Austria, Serbia
Interventions of the Project
Name of the intervention(*) : Placebo
Type of the intervention : Drug (including placebo)
Additional information about the intervention : Standard of care (SOC) + placebo p.o. (corresponding to 0.05, 0.07 or 0.1 mg digitoxin tablets)
Name(s) of the arm(s) associated with the given intervention : Control intervention
Name of the intervention(*) : Digitoxin
Type of the intervention : Drug (including placebo)
Additional information about the intervention : Standard of care (SOC) + digitoxin p.o. (0.05, 0.07, or 0.1 mg/die) Dose adjustment at week 6, and, if indicated, at week 12 after start of treatment. Target serum concentration of digitoxin 8 - 18 ng/ml (10.5 – 23.6 nmol/l)
Name(s) of the arm(s) associated with the given intervention : Experimental intervention
Exposures of the Project
Name of the exposure : Not specified
Type of the exposure : Not specified
Additional information about the exposure : Not specified
Name(s) of the group(s) associated with the given exposure : Not specified
Outcome measures in the Project
Name of the outcome measure(*) : Composite endpoint of time to all-cause mortality and hospital admission for worsening heart failure (whatever occurs first)
Description of the outcome measure : Not specified
Type of the outcome measure : Primary
Time point(s) of assessment : Not specified
Name of the outcome measure(*) : Time to all-cause mortality
Description of the outcome measure : Not specified
Type of the outcome measure : Secondary
Time point(s) of assessment : Not specified
Name of the outcome measure(*) : Recurrent hospital admission for worsening heart failure and terminal event of all-cause mortality
Description of the outcome measure : Not specified
Type of the outcome measure : Secondary
Time point(s) of assessment : Not specified
Name of the outcome measure(*) : Each component of the primary endpoint (hospital admission for worsening heart failure, all-cause mortality), cardiovascular mortality, death from heart failure, any non-cardiovascular death, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, any cardiovascular hospitalization, hospital admission for any cause, implantation of a cardioverter-defibrillator, implantation of a cardiac-resynchronisation device, implantation of a pacemaker, sudden cardiac death, change in functional capacity assessed by NYHA class and quality of life assessed by the SF-12.
Description of the outcome measure : Not specified
Type of the outcome measure : Secondary
Time point(s) of assessment : Not specified
Name of the outcome measure(*) : Assessment of safety
Description of the outcome measure : Adverse events (AEs), serious adverse events (SAEs) and laboratory abnormalities will be compared between the treatment groups.
Type of the outcome measure : Other
Time point(s) of assessment : Not specified
Additional information about the Project : Not specified
Additional assessments/measurements in the Project : []
Data sharing strategy of the Project(*)
Is it planned to share the data?(*) : Not specified
Supporting documents available in addition to the data : Data dictionary, Study protocol, Protocol amendment
When and for how long will the data be available? : Not specified
Criteria for data access : Not specified
Additional information about data sharing : Not specified
DataSHIELD/Opal infrastructure available? : Not specified
Link to data request application : Not specified
Web page with additional information about data sharing : Not specified
Record linkage possible? : false
Non-interventional aspects of the Project
Temporal design : []
Target follow-up duration of the Project
Target follow-up duration(*) : Not specified
Unit of time(*) : Not specified
Number of follow-ups conducted : Not specified
Biosamples retained in a biorepository : []
Specific types of retained biosamples : Not specified
Interventional aspects of the Project
Numerical phase : Phase-4
Masking of intervention(s) assignment
Masking implemented? : true
Who is masked? : Participant, Care provider, Investigator, Outcomes assessor
Additional information about masking : Not specified
Type of allocation of participants to an arm : Randomized
Off-label use of a drug product : No

Annotated Properties

Topic annotations

Cardiology

DIGIT-HF

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