Digoxin Short Term Treatment Assessment Randomized Trial in AHF

Acute Heart Failure Clinical Trial

— DIG-STA-AHF  

Official title:

Assessment of the Efficacy and Safety of a Short Term Treatment With Digoxin on Patients With Acute Heart Failure Syndromes. A Randomized Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02544815
• Other study ID #: Digoxin - START - AHF
• Status: Recruiting
• Phase: Phase 3
• Start date: May 1, 2023
• Est. completion date: July 31, 2025

Study information

• Verified date: December 2023
• Source: University of Monastir
• Contact: Nouira Semir, Professor
• Phone: 73106000
• Email: semir.nouira[@]rns.tn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

AHFS management is challenging and most of the used drugs has failed to decrease post-discharge mortality and readmission rates which represent the most important goal in AHFS.

Digoxin processes many characteristics of a beneficial drug for heart failure, however recent publications has rose concerns about its safety profile and therefore decreasing its use.

Whether digoxin is efficient and safe in short term treatment of acute heart failure is a question that should be studied.

Description:

AHFS management is challenging given the heterogeniety of the patient population, absence of a universally accepted definition, incomplete understanding of its pathophysiology, and lack of evidence based guidelines.

The majority of patients appear to respond well to initial therapies consisting of loop diuretics and vasoactive agents. however, this treatments failed to decrease post-discharge mortality and readmission rates which represent the most important goal in AHFS.

In the last few years, many drugs has been tested in AHFS setting trying to adress this issue, however results has been disappointing in term of efficacy and / or safety.

Although evidence supports the beneficial effects of digoxin on hemodynamic, neurohormonal, and electrophysiological parameters in patients with CHF, recent publications has rose concerns about its safety profile and therefore decreasing its use.

The effects of digoxin alone or in combination with other vasodilators are seen within few hours of its administration and result in increased cardiac output, decreased pulmonary wedge pressure, increased ejection fraction, and improved neurohormonal profile without changes in blood pressure.

All this findings made us rose the question of whether digoxin is effective or not in short term treatment of acute heart failure ? Additionnel treatments for AHF were given according left to ACCF/AHA for the managementof heart failure .

Blood testing for scanner digoxin magerments will be confirmed at H8, h24 and H72 after the post protocol treatment admession treatment administration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: July 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Able to provide informed written consent.

• Male or female aged =18 years old.

• Admitted for acute heart failure defined by the presence of dypnea at rest or with minimal exertion , pulmonary congestion on chest radiograph ; and increased natriutic peptide concentrations ( BNP >=350 pg/ml) or NTproBNP >=1400 pg/ml ) .

• Able to be randomized within 12 hours from presentation to the hospital.

Exclusion Criteria:

• Pregnant or breast feeding women.

• Known severe or terminal renal failure.

• Previous hepatic impairment.

• Major surgery within 30 days.

• Hematocrit < 25%.

• Alteration of consciousness GCS < 15

• Critically ill patients needing immediate mechanical hemodynamic of ventilatory support.

• Confirmed or suspected diagnosis of ACS within 45 days before inclusion.

• Severe arrhythmias including significant sinoatrial or atrioventricular blocks or WPW syndrome.

• Implantable cardiac devices including pacemakers and defibrillators.

• Hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.

• Noncardiac pulmonary edema, including suspected sepsis.

• Severe pulmonary disease

• Significant stenotic valvular disease .

• Hyperkalemia > 5.5 mmol /L .

• Administration of an investigational drug or implantation of an investigational device or participation in another trial within 30 days before screening.

• Previous treatment with digoxin within 15 days before inclusion or contra-indications to digoxin.

• Inability to follow instructions or comply with follow-up procedures.

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• Digoxin
Digoxin 0.25 mg pills
• Placebo
Placebo pills

Locations

Country	Name	City	State
Tunisia	Sahloul University Hospital	Hammam sousse	Sousse
Tunisia	Fattouma Bourguiba University Hospital	Monastir

Sponsors (1)

Lead Sponsor	Collaborator
University of Monastir

Country where clinical trial is conducted

Tunisia, 

References & Publications (3)

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. — View Citation

Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, Massie BM, Roland E, Targum S, Collins SP, Filippatos G, Tavazzi L; International Working Group on Acute Heart Failure Syndromes. Acute heart failure syndromes: current state and framework for future research. Circulation. 2005 Dec 20;112(25):3958-68. doi: 10.1161/CIRCULATIONAHA.105.590091. No abstract available. — View Citation

Hashim T, Elbaz S, Patel K, Morgan CJ, Fonarow GC, Fleg JL, McGwin G, Cutter GR, Allman RM, Prabhu SD, Zile MR, Bourge RC, Ahmed A. Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. Am J Med. 2014 Feb;127(2):132-9. doi: 10.1016/j.amjmed.2013.08.006. Epub 2013 Sep 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30 days mortality and rehospitalization rate		30 days
Secondary	Hemodynamic improvement	Change in hemodynamic parameters as quantified by the area under the curve of bio-impedance thoracic fluid contenant (TFC), lung ultrasound (LUS) congestion score and BNP serum levels, from baseline to day 3.	3 days
Secondary	Need for hospitalization		3 days
Secondary	Length of stay in hospital		from baseline to hospital discharge
Secondary	AUC of dyspnea VAS scores	Change in patient-reported dyspnea as quantified by the area under the curve (AUC) of visual analogue scale (VAS) scores (0-100 mm scale) : a dyspnea VAS score of 0 corresponds to the patient's subjective feeling of "I Can Breathe Normally" and a dyspnea VAS score of 100 corresponds to "I Can't Breathe At All.	3 days
Secondary	Improvement of patient-reported dyspnea	Improvement of patient-reported dyspnea relative to the start of study drug using a 5 point likert scale at 6, 12, and 24 hours, where a responder was a patient with better or markedly betted dyspnea at all three of those time points.	[Time Frame: 6, 12, and 24 hours from start of the study medication]
Secondary	Dyspnea resolution time	defined as the time between the start of study drug and the reduction of at least 50% of the dyspnea VAS score from baseline.	3 days
Secondary	Digoxin related adverse events	Occurrence of major adverse events related to digoxin and implicating its discontinuation.; Admitted major side effects of digoxin are: Severe ventricular arrhythmias including ventricular tachycardia or fibrillation, Severe bradycardia, Second- or third-degree heart block not responsive to atropine, Serum potassium levels exceeding 5.5 mEq/L with rapidly progressive signs and symptoms of digoxin toxicity, Neurologic symptoms (eg, visual disturbances, disorientation, and confusion).	30 days
Secondary	Worsening renal function	worsening renal function under treatment is defined as a relative increase in serum creatinine of at least 25% from baseline value.	30 days