DECISION; Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

1 Nov 2024 → 19 Nov 2025

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509898-23-00

EudraCT number

2018-003789-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To study whether low-level digoxin reduces the composite primary endpoint of (repeated) HF hospitalizations, (repeated) urgent HF
hospital visits and cardiovascular mortality, compared to placebo, in chronic HF.

Conditions and MedDRA coding

heart failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18year
2. Outpatients with chronic HF, NYHA II - ambulatory IV
3. LVEF ≤50%
4. Serum NT-proBNP concentrations (max 1 month old): Previous HF hospitalization ≤ 1 year before randomisation ≥400pg/mL if sinus rhythm; ≥800pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in the absence of HF hospitalizations ≥ 600pg/mL if sinus rhythm; ≥1000 pg/mL. if AF BNP concentrations (max 1 month old): Previous HF hospitalization ≤ 1 year before randomisation ≥100pg/mL if sinus rhythm; ≥200pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in absence of HF hospitalization ≥150pg/mL if sinus rhythm; ≥250pg/mL if AF.
5. ≥14 days stable on guideline-recommended therapy (doses and number of therapies as tolerated by each patient)

Exclusion criteria 18

1. Heart rate ≤60bpm (if sinus rhythm); heart rate ≤70bpm (if AF)
2. History of HF hospitalization ≤7days
3. History of myocardial infarction, myocarditis, percutaneous intervention, RCT, pacemaker/ICD implantation, cardiac surgery or stroke ≤30 days
4. Estimated glomerular filtration rate (eGFR), ≤30ml/min/1.73m2 (max 1 month old)
5. The presence of a mechanical assist device
6. Use of inotropic drugs (dopamine, dobutamine, (nor)adrenaline, and milrinon)
7. Scheduled for mechanical assist device or heart transplant
8. Other non-cardiac conditions with limited life expectancy (≤ duration of the study)
9. Amyloid, hypertrophic obstructive or constrictive cardiomyopathy
10. Accessory atrio-ventricular pathway (e.g. Wolf-Parkinson-White syndrome)
11. (Intermittent) complete heart block or second-degree AV block type Mobitz without pace maker or ICD
12. Severe (grade III/III) aortic valve disease
13. Complex congenital heart disease
14. Proven hypersensitivity to digoxin (prior side effects)
15. Concomitant medication that interacts with digoxin (see appendix 2, prohibited medication)
16. Use of digoxin ≤6 months prior to inclusion
17. Participation in another (intervention) clinical trial (registry studies not included)
18. Women who are pregnant, breastfeeding or may be considering pregnancy during the study period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the composite of (repeated) HF hospitalizations, (repeated) urgent HF hospital visits and cardiovascular death.

Secondary endpoints 14

1. All-cause mortality
2. Cardiovascular death.
3. (Repeated) HF hospitalization
4. (repeated) urgent HF hospital visits
5. Cost-effectiveness.
6. All-cause hospitalizations.
7. Unscheduled cardiovascular hospital visits.
8. Days alive out of hospital.
9. Quality of Life.
10. Heart rate in both AF and sinus rhythm.
11. To assess side effects (including SUSARs) associated with study medication.
12. Initiation of (recurrence of) AF in patients with sinus rhythm at baseline.
13. Conversion to sinus rhythm and maintenance of sinus rhythm in patients with AF at baseline
14. Proteomics and validating hits in elisa's

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Ester Maas

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Ester Maas

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications