Clinical trial NCT02544815: Digoxin Short Term Treatment Assessment Randomized Trial in 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Heart Failure
Keywords: digoxin, eficacy, safety
Lead sponsor: University of Monastir
Sponsor class: OTHER
First posted: 2015-09-09
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 30 days mortality and rehospitalization rate
timeFrame: 30 days
Secondary outcomes:
measure: Hemodynamic improvement
timeFrame: 3 days
measure: Need for hospitalization
timeFrame: 3 days
measure: Length of stay in hospital
timeFrame: from baseline to hospital discharge
measure: AUC of dyspnea VAS scores
timeFrame: 3 days
measure: Improvement of patient-reported dyspnea
timeFrame: [Time Frame: 6, 12, and 24 hours from start of the study medication]
measure: Dyspnea resolution time
timeFrame: 3 days
measure: Digoxin related adverse events
timeFrame: 30 days
measure: Worsening renal function
timeFrame: 30 days
Other outcomes:
Locations:
city: Hammam sousse
country: Tunisia
facility: Sahloul University Hospital
state: Sousse
city: Monastir
country: Tunisia
facility: Fattouma Bourguiba University Hospital
Study officials:
affiliation: University Hospital of Monastir
name: Nouira Semir, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.