- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02544815
Digoxin Short Term Treatment Assessment Randomized Trial in AHF (DIG-STA-AHF)
Assessment of the Efficacy and Safety of a Short Term Treatment With Digoxin on Patients With Acute Heart Failure Syndromes. A Randomized Controlled Trial.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Nouira Semir, Professor
- Phone Number: 00216 73106000
- Email: semir.nouira@rns.tn
Study Contact Backup
- Name: Bzeouich Nasri, MD
- Phone Number: 00216 52919170
- Email: medecinasri@gmail.com
Study Locations
-
-
-
Monastir, Tunisia, 5000
- Recruiting
- Fattouma Bourguiba University Hospital
-
Contact:
- Nouira Semir, Professor
- Phone Number: 00216 73641144
- Email: semir.nouira@rnu.tn
-
Contact:
- nasri Bzeouich, MD
- Phone Number: 00216 52919170
- Email: medecinasri@gmail.com
-
Principal Investigator:
- Nouira Semir, Professor
-
Sub-Investigator:
- Beltaief Kaouthar, MD
-
Sub-Investigator:
- Bzeouich Nasri, MD
-
-
Sousse
-
Hammam sousse, Sousse, Tunisia, 4011
- Recruiting
- Sahloul University Hospital
-
Contact:
- Boukef Riadh, Professor
- Phone Number: 00216 73460678
- Email: riadh.boukef@rnu.tn
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Digoxin
Oral digoxin 0.25 mg: one pill per day for 30 consecutive days.
|
Digoxin 0.25 mg pills
|
Placebo Comparator: Placebo
Oral placebo for 30 days.
|
Placebo pills
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
30 days mortality and rehospitalization rate
Time Frame: 30 days
|
30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hemodynamic improvement
Time Frame: 3 days
|
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
|
Need for hospitalization
Time Frame: 3 days
|
3 days
|
|
Length of stay in hospital
Time Frame: from baseline to hospital discharge
|
from baseline to hospital discharge
|
|
Improvement of patient-reported dyspnea
Time Frame: [Time Frame: 6, 12, and 24 hours from start of the study medication]
|
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]
|
Dyspnea resolution time
Time Frame: 3 days
|
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
|
Digoxin related adverse events
Time Frame: 30 days
|
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
|
Worsening renal function
Time Frame: 30 days
|
worsening renal function under treatment is defined as a relative increase in serum creatinine of at least 25% from baseline value.
|
30 days
|
AUC of dyspnea VAS scores
Time Frame: 3 days
|
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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Digoxin related adverse events
Time Frame: from administration of study drug to 30 days after
|
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). |
from administration of study drug to 30 days after
|
Worsening renal function
Time Frame: from administration of study drug to 30 days after
|
Worsening of renal function rates within day 30 from starting of the study treatment. Worsening renal function under treatment is defined as a relative increase in serum creatinine of at least 25% from baseline value. |
from administration of study drug to 30 days after
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nouira Semir, Professor, University Hospital of Monastir
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Digoxin - START - AHF
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Heart Failure
-
Idorsia Pharmaceuticals Ltd.CompletedAcute Heart Failure | Acute Decompensation of Chronic Heart Failure | New Onset of Heart FailureUnited States, United Kingdom, Israel, Switzerland, Austria, Denmark, France, Germany, Greece, Poland
-
Idorsia Pharmaceuticals Ltd.CompletedAcute Heart Failure | Acute Decompensation of Chronic Heart Failure | New Onset of Heart FailureUnited States, Hungary, Australia, Czechia, Germany, Italy, Norway, United Kingdom
-
Abiomed Inc.RecruitingHeart Diseases | Acute Decompensated Heart Failure | Congestive Heart Failure | Acute Heart FailureUnited States
-
Shanghai Chest HospitalUnknownAcute Renal Failure | Acute Heart FailureChina
-
Magenta Medical Ltd.TerminatedCongestive Heart Failure | Heart Failure, Congestive | Acute Heart FailureCroatia, Belgium, Serbia
-
University Medical Center GroningenCompletedHeart Failure; With Decompensation | Heart Failure,Congestive | Heart Failure AcuteNetherlands
-
Jordan Cardio Vascular Research GroupRecruitingHeart Failure | Chronic Heart Failure | Acute Heart FailureJordan
-
University Hospital, Clermont-FerrandHospices Civils de Lyon; University Hospital, Grenoble; Hôpital de la Croix-Rousse and other collaboratorsRecruitingHeart Failure | Chronic Heart Failure | Acute Heart FailureFrance
-
Azienda Ospedaliera Città della Salute e della...Caretek S.r.l. Turin, Italy; Santer Reply S.p.A. Milan, ItalyUnknownHeart Failure; With Decompensation | Heart Failure,Congestive | Heart Failure AcuteItaly
-
Indiana UniversityWayne State University; Vanderbilt University; Case Western Reserve University; Inova Fairfax HospitalCompletedHeart Failure | Acute Cardiac Failure | Acute Cardiac Pulmonary Edema | Heart Failure AcuteUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States