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出境医 / 临床实验 / Sodium-glucose Co-transporter 2 Inhibitors Effects in Failing Heart Patients

Sodium-glucose Co-transporter 2 Inhibitors Effects in Failing Heart Patients

Study Description
Brief Summary:
SLGT2 therapy is safety used in heart failure (HF) patients with depressed left ventricle ejection fraction (LVEF) and diabetes mellitus (DM). These patients experience higher rate of ventricular arrhythmias (VA), that are a leading cause of cardiac arrest and mortality. However, these patients are treated by implantable cardioverter defibrillator (ICD) and cardiac resynchronization with defbrillator devices (CRTd) implant. In this setting, the catheter ablation (CA) treatment has been used to reduce the ventricular arrhythmias and the ICD/CRTds' interventions, and to prevent mortality events in these' patients. On other hand, still a higher percentage of patients result as non responders to an ablative approach with higher acute and long term mortality rate. Therefore, in the present study in a population of HF patients (DM vs. non DM patients) affected by VA, authors will investigate the effects of CA on mortality rate at 12 months of follow up. In addition, authors would demonstrate the ameliorative effects of new hypoglycemic drugs in addition to CA in patients with DM. However, after CA the patients with DM will be randomly assigned to SGLT2 therapy vs. placebo. Indeed, study hypothesis will be that, a) DM vs. non DM patients might have higher mortality rate after CA; b) patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo might experience a lower rate of mortality at 1 year of follow-up.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Heart Failure Ventricular Arrythmia Drug: SLGT2 Drug: Placebo Phase 4

Detailed Description:
SLGT2 therapy is safety used in heart failure (HF) patients with depressed left ventricle ejection fraction (LVEF) and diabetes mellitus (DM). Indeed, in these patients SGLT2 therapy reduces hospital admission for heart failure and mortality rate. To date, these patients experience higher rate of ventricular arrhythmias (VA), that are a leading cause of cardiac arrest and mortality. However, as indicated by international guidelines, these patients can be treated by implantable cardioverter defibrillator (ICD) and CRTd as primary and/or secondary prevention therapy. Consequently, the effectiveness of ICD and CRTd is to treat sustained VA, and to reduce cardiac arrest events and mortality. Indeed, ICDs/CRTds' anti-tachycardia pacing and shocks can interrupt VA, and this might prevent a cardiac arrest event. This therapeutic effect can positively impact on acute and long term patients' survival. On other hand, authors showed that, continuous VA events and ICDs' interventions are causes of reduced patients' life expectancy in HF patients. This worse prognosis is particularly evidenced in failing heart patients with DM as compared to patients without DM. In this setting, the catheter ablation (CA) treatment has been used to reduce the ventricular arrhythmias and the ICDs/CRTds' interventions, and to prevent mortality events in these patients. On other hand, still a higher percentage of patients result as non responders to an ablative approach with higher acute and long term mortality rate. Among these non responders patients to an ablative approach, DM is a negative prognostic factor. Therefore, in the present study in a population of HF patients (DM vs. non DM patients) with VA authors will investigate the effects of CA on mortality rate at 12 months of follow up. In addition, authors would like to demonstrate the ameliorative effects of new hypoglycemic drugs in addition to CA in patients with DM. However, after CA the patients with DM will be randomly assigned to SGLT2 therapy vs. placebo. Indeed, study hypothesis will be that, a) DM vs. non DM might have higher mortality rate after CA; b) patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo might experience a lower rate of mortality at 1 year of follow-up. Therefore, study aim will be to demonstrate a reduction of VA, ICDs/CRTds' interventions, and mortality in patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo at 12 months of follow-up.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: Clinical Outcomes and Long Term Effects of Sodium-glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Failing Heart Patients With Implantable Cardioverter Defibrillator Undergoing Trans-catheter Ablation for Ventricular Arrhythmias.
Actual Study Start Date : January 1, 2017
Actual Primary Completion Date : January 1, 2019
Actual Study Completion Date : March 1, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: heart failure patients with diabetes treated by SGLT2 drugs
Patients affected by heart failure and diabetes mellitus. These patients previous received an internal cardioverter defibrillator (ICD), and then a catheter ablation for ventricular arrhythmias (VA) therapy. After CA these patients received SLGT2 therapy.
 Drug: SLGT2
These patients will receive SLGT2 therapy after catheter ablation.
Placebo Comparator: heart failure patients with diabetes treated by placebo
Patients affected by heart failure and diabetes mellitus. These patients previous received an internal cardioverter defibrillator (ICD), and then a catheter ablation for ventricular arrhythmias (VA) therapy. After CA these patients received placebo therapy.
 Drug: Placebo
These patients will receive placebo therapy after catheter ablation.
Outcome Measures
Primary Outcome Measures :
  1. all cause deaths [ Time Frame: 12 months ]
    after the intervention authors will evaluate all cause of deahs

  2. cardiac deaths [ Time Frame: 12 months ]
    after the intervention authors will evaluate the cause of cardiac deahs

  3. ventricular arrhythmias recurrence [ Time Frame: 12 months ]
    after the intervention authors will evaluate the cases of ventricular arrhythmias recurrences


Secondary Outcome Measures :
  1. hospitalization for heart failure worsening [ Time Frame: 12 months ]
    after the intervention authors will evaluate the causes of hospital re-admission for heart failure worsening


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • heart failure (HF) under optimal maximal drug therapy with NYHA functional II-III;
  • HF with prior echocardiographic evidence of left ventricular systolic dysfunction (LVEF <35 % or subjective assessment of LV dysfunction that is mild or worse);
  • patients under furosemide 80 mg daily or less, or equivalent loop diuretic;
  • patients with stable HF symptoms for at least 3 months prior to consent;
  • patients on stable therapy for HF for at least 3 months prior to consent;
  • patients without hospitalization for HF for at least 3 months prior to consent;
  • Ischemic and non ischemic dilated cardiomiopathy diagnosis;
  • patients with internal cardioverter defibrillator (ICD);
  • patients with cardioverter resynchronization therapy and defibrillator (CRTd);
  • patients with diagnosis of diabetes mellitus (DM);
  • patients aged >18 years and <75 years

Exclusion Criteria:

  • Patients without ICD;
  • patients without previous event of ventricular arrhythmia (VA);
  • patients without indication to receive catheter ablation (CA) for VA;
  • patients with type 1 diabetes mellitus;
  • severe hepatic disease, renal disease defined as chronic kidney disease stage 3b or worse (i.e. glomerular filtration rate <45 ml/min);
  • systolic blood pressure <95 mmHg at screening visit;
  • screening HbA1c <6.0 %;
  • patients unable to walk or to perform cardio pulmonary exercise testing or six minute walking test;
  • malignancy (receiving active treatment) or other life threatening diseases;
  • pregnant or lactating women;
  • patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days;
  • patients who were unable to give informed consent;
  • any other reason considered by a study physician to be inappropriate for inclusion.
Contacts and Locations

Locations
Layout table for location information
Italy
Raffaele Marfella
Naples, Italy, 80138
Sponsors and Collaborators
University of Campania "Luigi Vanvitelli"
Tracking Information
First Submitted Date  ICMJE June 5, 2019
First Posted Date  ICMJE June 6, 2019
Last Update Posted Date March 3, 2020
Actual Study Start Date  ICMJE January 1, 2017
Actual Primary Completion Date January 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • all cause deaths [ Time Frame: 12 months ]
    after the intervention authors will evaluate all cause of deahs
  • cardiac deaths [ Time Frame: 12 months ]
    after the intervention authors will evaluate the cause of cardiac deahs
  • ventricular arrhythmias recurrence [ Time Frame: 12 months ]
    after the intervention authors will evaluate the cases of ventricular arrhythmias recurrences
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019) 		hospitalization for heart failure worsening [ Time Frame: 12 months ]
after the intervention authors will evaluate the causes of hospital re-admission for heart failure worsening
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sodium-glucose Co-transporter 2 Inhibitors Effects in Failing Heart Patients
Official Title  ICMJE Clinical Outcomes and Long Term Effects of Sodium-glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Failing Heart Patients With Implantable Cardioverter Defibrillator Undergoing Trans-catheter Ablation for Ventricular Arrhythmias.
Brief Summary SLGT2 therapy is safety used in heart failure (HF) patients with depressed left ventricle ejection fraction (LVEF) and diabetes mellitus (DM). These patients experience higher rate of ventricular arrhythmias (VA), that are a leading cause of cardiac arrest and mortality. However, these patients are treated by implantable cardioverter defibrillator (ICD) and cardiac resynchronization with defbrillator devices (CRTd) implant. In this setting, the catheter ablation (CA) treatment has been used to reduce the ventricular arrhythmias and the ICD/CRTds' interventions, and to prevent mortality events in these' patients. On other hand, still a higher percentage of patients result as non responders to an ablative approach with higher acute and long term mortality rate. Therefore, in the present study in a population of HF patients (DM vs. non DM patients) affected by VA, authors will investigate the effects of CA on mortality rate at 12 months of follow up. In addition, authors would demonstrate the ameliorative effects of new hypoglycemic drugs in addition to CA in patients with DM. However, after CA the patients with DM will be randomly assigned to SGLT2 therapy vs. placebo. Indeed, study hypothesis will be that, a) DM vs. non DM patients might have higher mortality rate after CA; b) patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo might experience a lower rate of mortality at 1 year of follow-up.
Detailed Description SLGT2 therapy is safety used in heart failure (HF) patients with depressed left ventricle ejection fraction (LVEF) and diabetes mellitus (DM). Indeed, in these patients SGLT2 therapy reduces hospital admission for heart failure and mortality rate. To date, these patients experience higher rate of ventricular arrhythmias (VA), that are a leading cause of cardiac arrest and mortality. However, as indicated by international guidelines, these patients can be treated by implantable cardioverter defibrillator (ICD) and CRTd as primary and/or secondary prevention therapy. Consequently, the effectiveness of ICD and CRTd is to treat sustained VA, and to reduce cardiac arrest events and mortality. Indeed, ICDs/CRTds' anti-tachycardia pacing and shocks can interrupt VA, and this might prevent a cardiac arrest event. This therapeutic effect can positively impact on acute and long term patients' survival. On other hand, authors showed that, continuous VA events and ICDs' interventions are causes of reduced patients' life expectancy in HF patients. This worse prognosis is particularly evidenced in failing heart patients with DM as compared to patients without DM. In this setting, the catheter ablation (CA) treatment has been used to reduce the ventricular arrhythmias and the ICDs/CRTds' interventions, and to prevent mortality events in these patients. On other hand, still a higher percentage of patients result as non responders to an ablative approach with higher acute and long term mortality rate. Among these non responders patients to an ablative approach, DM is a negative prognostic factor. Therefore, in the present study in a population of HF patients (DM vs. non DM patients) with VA authors will investigate the effects of CA on mortality rate at 12 months of follow up. In addition, authors would like to demonstrate the ameliorative effects of new hypoglycemic drugs in addition to CA in patients with DM. However, after CA the patients with DM will be randomly assigned to SGLT2 therapy vs. placebo. Indeed, study hypothesis will be that, a) DM vs. non DM might have higher mortality rate after CA; b) patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo might experience a lower rate of mortality at 1 year of follow-up. Therefore, study aim will be to demonstrate a reduction of VA, ICDs/CRTds' interventions, and mortality in patients with DM treated by CA plus SLGT2 therapy vs. patients with DM treated by CA plus placebo at 12 months of follow-up.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE
  • Diabetes Mellitus
  • Heart Failure
  • Ventricular Arrythmia
Intervention  ICMJE
  • Drug: SLGT2
    These patients will receive SLGT2 therapy after catheter ablation.
  • Drug: Placebo
    These patients will receive placebo therapy after catheter ablation.
Study Arms  ICMJE
  • Experimental: heart failure patients with diabetes treated by SGLT2 drugs
    Patients affected by heart failure and diabetes mellitus. These patients previous received an internal cardioverter defibrillator (ICD), and then a catheter ablation for ventricular arrhythmias (VA) therapy. After CA these patients received SLGT2 therapy.
    Intervention: Drug: SLGT2
  • Placebo Comparator: heart failure patients with diabetes treated by placebo
    Patients affected by heart failure and diabetes mellitus. These patients previous received an internal cardioverter defibrillator (ICD), and then a catheter ablation for ventricular arrhythmias (VA) therapy. After CA these patients received placebo therapy.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 5, 2019) 		100
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 1, 2019
Actual Primary Completion Date January 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • heart failure (HF) under optimal maximal drug therapy with NYHA functional II-III;
  • HF with prior echocardiographic evidence of left ventricular systolic dysfunction (LVEF <35 % or subjective assessment of LV dysfunction that is mild or worse);
  • patients under furosemide 80 mg daily or less, or equivalent loop diuretic;
  • patients with stable HF symptoms for at least 3 months prior to consent;
  • patients on stable therapy for HF for at least 3 months prior to consent;
  • patients without hospitalization for HF for at least 3 months prior to consent;
  • Ischemic and non ischemic dilated cardiomiopathy diagnosis;
  • patients with internal cardioverter defibrillator (ICD);
  • patients with cardioverter resynchronization therapy and defibrillator (CRTd);
  • patients with diagnosis of diabetes mellitus (DM);
  • patients aged >18 years and <75 years

Exclusion Criteria:

  • Patients without ICD;
  • patients without previous event of ventricular arrhythmia (VA);
  • patients without indication to receive catheter ablation (CA) for VA;
  • patients with type 1 diabetes mellitus;
  • severe hepatic disease, renal disease defined as chronic kidney disease stage 3b or worse (i.e. glomerular filtration rate <45 ml/min);
  • systolic blood pressure <95 mmHg at screening visit;
  • screening HbA1c <6.0 %;
  • patients unable to walk or to perform cardio pulmonary exercise testing or six minute walking test;
  • malignancy (receiving active treatment) or other life threatening diseases;
  • pregnant or lactating women;
  • patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days;
  • patients who were unable to give informed consent;
  • any other reason considered by a study physician to be inappropriate for inclusion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03977116
Other Study ID Numbers  ICMJE SecondUNI 05.06.2019
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Celestino Sardu, University of Campania "Luigi Vanvitelli"
Study Sponsor  ICMJE University of Campania "Luigi Vanvitelli"
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Campania "Luigi Vanvitelli"
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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