Effects of Digoxin in Modern Heart Failure Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unidade Local De Saude De Sao Jose E.P.E.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Oct 2024 → 10 Mar 2026

Decision date (initial)

2024-09-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Unidade Local de Saúde de São José, EPE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the effectiveness of Digoxin in functional capacity and cardiac function when combined with standard of care modern heart failure treatment.

Secondary objectives 2

1. To evaluate the safety of Digoxin in patients with heart failure on top of standard of care treatment.
2. To evaluate the effect of Digoxin on quality of life in patients with heart failure on top of standard of care treatment.

Conditions and MedDRA coding

Heart Failure

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Chronic heart failure with reduced ejection fraction (LVEF ≤45%) with at least 6 months of maximally tolerated class I medications (ARNi or ACEiplus beta-blockers plus SGLT2 inhibitors plus MRA) unless contraindicated.
2. Symptomatic heart failure with at least New York Heart Association (NYHA) class ≥ II in which Digoxin may be considered according tocurrent European Guidelines.
3. Age ≥ 18 years old.
4. Ability to provide informed consent and willingness to comply with studyprocedures.

Exclusion criteria 17

1. Already using Digoxin or having used it on the last 9 days (washout period).
2. Persistent potassium below 3.2 mmol/L.
3. Persistent hypercalcaemia or hypomagnesaemia.
4. Sick sinus syndrome without pacemaker or Implantable cardioverter-defibrillators (ICD).
5. Grade II-III AV block without a pacemaker or ICD.
6. Wolff-Parkinson-White syndrome.
7. Heart rate below 55 bpm at rest in sinus rhythm or below 70 bpm in AF in patients without CRT or cardiac physiologic pacing.
8. Age < 18 years old.
9. Hypersensitivity to Digoxin, other digitalis glycosides or to any of the excipients
10. Pregnant or lactating women. Woman of childbearing potential who do not accept to use the methods of contraception suggested for the trial.
11. New heart failure medication in the previous 6 months.
12. Change in class I HF dose (ARNi, ACEi, ARB, beta-blockers, SGLT2 inhibitors or MRA) in the previous 3 months.
13. Recent (<6 months): myocardial infarction, coronary revascularization, surgery or catheter intervention for valvular heart disease, stroke, or cerebral ischaemia, start of heart failure device therapy potentially improving left ventricular ejection fraction or HF symptoms (e.g. cardiac resynchronization therapy, cardiac contractility modulation, baroreflex activation therapy)
14. Significant renal insufficiency (Glomerular filtration rate (GFR) ≤ 15mL/min) as evaluated by the Cockcroft-Gault formula.
15. NTproBNP values < 125pg/mL.
16. Ventricular tachycardia or ventricular fibrillation
17. Arrhythmias caused by cardiac glycoside intoxication

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Peak oxygen consumption measured by Cardiopulmonary Exercise Test at 24 weeks.
2. Global Work Index measured by Echocardiography at 24 weeks.

Secondary endpoints 6

1. Composite of death, hospitalizations, and ventricular arrhythmia from baseline to 24 weeks.
2. KCCQ-12 Score at 24 weeks.
3. Changes in analytical parameters at 24 weeks: NTproBNP, Glomerular filtration rate, urine ratio of albumin/creatinine, C-reactive protein, aldosterone and renin plasma values.
4. Cardiopulmonary exercise test parameters at 24 weeks: Peak oxygenconsumption (percentage of predicted), Oxygen consumption at anaerobic threshold, VE/VCO2 slope, Duration of exercise, Optimal point of ventilation.
5. ECG parameters at 24 weeks: QRS interval.
6. Echocardiography parameters at 24 weeks: Global Constructive Work, Global Wasted Work, Global Work Efficiency, Global Longitudinal Strain, Left Ventricular Ejection Fraction, Right ventricular fractional area change, Free-wall right ventricle longitudinal strain, Left ventricle end-diastolic volume, Left Atrial Reservoir Strain, Mechanical dispersion, E/e´

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unidade Local De Saude De Sao Jose E.P.E.

Sponsor organisation

Unidade Local De Saude De Sao Jose E.P.E.

Address

Rua Jose Antonio Serrano

City

Lisbon

Postcode

1150-199

Country

Portugal

Scientific contact point

Organisation

Unidade Local De Saude De Sao Jose E.P.E.

Contact name

Coordinator of the Research Centre

Public contact point

Organisation

Unidade Local De Saude De Sao Jose E.P.E.

Contact name

Research Centre

Third parties 1

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 19 files

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

Application history

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