Advanced systolic chronic heart failure NYHA class III-IV and EF = 40% or NYHA class II and EF = 30% MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Digimerck® pico 0,05 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: DIGITOXIN
CAS Number: 71-63-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 438 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1752
Exclusion criteria
Exclusion criteria: 1. Recent ( 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. hyperpara-thyroidism, 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 < 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate in a large and simple clinical trial-approach that digitoxin (target serum concentrations preferably 8 - 18 ng/ml (10.5 – 23.6 nmol/l)) on top of standard of care is superior in reducing a composite of all-cause mortality and hospitalization for worsening heart failure (whichever occurs first) in patients with advanced systolic chronic heart failure (NYHA class III-IV and EF = 40% or NYHA class II and = 30%) to a greater extent compared to standard care plus placebo.;Secondary Objective: Not applicable;Primary end point(s): Composite endpoint of time to all-cause mortality and hospital admission for worsening heart failure (whatever occurs first) Admission for worsening heart failure is defined by presence of the following points together: 1.) Worsening of heart failure based on clinical judgment (presence of heart failure symptoms) by the treating physician. 2.) hospital stay overnight (= date change) 3.) i.v.-treatment with diuretics or vasoactive substances (e. g. nitroglycerine) or inotropes (e. g. dobutamine) ;Timepoint(s) of evaluation of this end point: week 6, week 12, month 6 and thereafter every 6 months until end of IMP treatment at termination visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints: 1) Time to all-cause mortality 2) Recurrent hospital admission for worsening heart failure and terminal event of all-cause mortality Ohter secondary endpoints: 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 cardiacresynchronisation 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. ;Timepoint(s) of evaluation of this end point: week 6, week 12, month 6 and thereafter every 6 months until end of IMP treatment at termination visit | — |
Countries
Austria, Germany, Serbia
Contacts
Public ContactProf. Dr. Udo Bavendiek
Hannover Medical School, Department of Cardiology and Angiology
Outcome results
None listed