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Administration of the SGLT-2 Inhibitor Dapagliflozin in the Patients With Amyloid Cardiomyopathy

Primary Purpose

Heart Failure With Reduced Ejection Fraction, Heart Failure With Preserved Ejection Fraction, Heart Failure With Mid Range Ejection Fraction

Status
Recruiting
Phase
Not Applicable
Locations
Russian Federation
Study Type
Interventional
Intervention
Dapagliflozin 10mg Tab
Placebo
Sponsored by
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring heart failure, amyloidosis, cardiomyopathy, amyloid cardiomyopathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Males and females between 18 and 80 years of age HF, confirmed with the increased level of NT-proBNP>300 pg/mL or BNP>100 pg/mL Transthyretin amyloid cardiomyopathy, confirmed with echocardiography and/or contrast-enhanced cardiac MRI Exclusion Criteria: The inability to continue all the activities planned in this study by the patient. The onset of pregnancy. Patient's voluntary withdrawal of consent to participate in a clinical trial at any point during the conduct of the study. Development of intolerable side effects. Administration of disease-modifying treatment of amyloidosis.

Sites / Locations

  • National Medical Research Center for Cardiology, Ministry of Health of Russian FederationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapagliflozine group

Control group

Arm Description

20 patients diagnosed with heart failure and amyloid cardiomyopathy, regardless of HF phenotype, are planned to be enrolled in the study. Patients with the edematous syndrome are allowed to participate in the study, but the condition of stable hemodynamics must be observed. Regardless of the group, patients will receive standard therapy for ADHF (diuretics and MRA). Patients will not receive beta-blockers/ACE-I/ARNI. In the treatment group the therapy will include the SGLT-2 inhibitor dapagliflozin, which will be prescribed during the first 24 hours after the hospitalization.

In the control group, patients will be treated with standard diuretic therapy without SGLT-2 inhibitors.

Outcomes

Primary Outcome Measures

Effect of dapagliflozin on quality of life using Kansas City Cardiomyopathy Questionnaire Summary Score (KCCQ-SC)
Changes in KCCQ score will be assessed
Effect of Dapagliflozin on 6 Minute Walk Test Distance
Changes in 6MWT score will be assessed
Effect of dapagliflozin on N-terminal Pro B-type Natriuretic Peptide (NTproBNP)
Changes in concentration of NT-proBNP will be assessed

Secondary Outcome Measures

Cardiovascular death + number of hospitalizations due to heart failure
Effect of dapagliflozin on change in echocardiographic parameters
Left ventricular ejection fraction will be assessed
Effect of dapagliflozin on change in specle-tracking echocardiographic parameters
Global longitudinal strain will be assessed

Full Information

First Posted
January 20, 2023
Last Updated
March 20, 2023
Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
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1. Study Identification

Unique Protocol Identification Number
NCT05795400
Brief Title
Administration of the SGLT-2 Inhibitor Dapagliflozin in the Patients With Amyloid Cardiomyopathy
Official Title
Administration of the SGLT-2 Inhibitor Dapagliflozin in the Patients With Amyloid Cardiomyopathy: a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Efficacy and safety of early administration of the SGLT-2 inhibitor dapagliflozin will be evaluated in patients with HF, regardless of LVEF, due to amyloid cardiomyopathy.
Detailed Description
Amyloidosis is an infiltrative disease in which fibrillar glycoprotein amyloid is deposited in the tissues. The prevalence of amyloidosis remains largely unexplored, but if the wild type of transthyretin amyloidosis is considered, it still remains significantly underestimated in the population. Among patients hospitalized for heart failure with a preserved left ventricular ejection fraction (HFpEF), 13% are later diagnosed with amyloid cardiomyopathy (AC), in 20-25% of patients over 80 years old AC is a finding of pathologists, and in the oldest group of patients over 97 years old AC is identified in 37% of cases. Hereditary transthyretin amyloidosis occurs at less than 8.8 cases per 1 million population in non-endemic areas (e.g., Sicily) and 1 case per 1000 population in endemic areas (e.g., Portugal). Thus, the prevalence of amyloid cardiomyopathy as the cause of HFpEF is underestimated. One of the manifestations of systemic amyloidosis is amyloid cardiomyopathy, when amyloid is deposited in the myocardium. This leads to thickening walls (phenotype of hypertrophic cardiomyopathy) and impaired relaxation processes, leading to diastolic myocardial dysfunction up to restrictive disorders (restrictive cardiomyopathy phenotype). Thus, in patients with amyloid cardiomyopathy HFpEF develops, and with the progression of the disease - heart failure with the mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction. The tragedy of situation lies in the fact that the specific (disease-modifying) treatment aimed at stopping or delaying amyloid deposition is limited to only two types of amyloidosis: AL and ATTR. As for the symptomatic treatment of HF, unfortunately, according to specific changes in hemodynamics, even with the reduced LVEF, therapy with beta-blockers, ACE-I/ARB/ARNI should be canceled. Currently, with the manifestation of the symptoms of HF, strict control over the drinking regimen and hydrobalance is necessary, and salt intake should be limited. In case of oedema, treatment with loop diuretics, MRA should be administrated. To date, in the treatment of HF, both with the reduced and preserved LVEF, another group of drugs has appeared - sodium-glucose cotransporter-2 (SGLT-2) inhibitors. However, in all studies conducted, the presence of HCM/RCM was the non-inclusion criteria in the investigation. At the same time, this group of drugs, unlike beta-blockers/ACE-I/ARNI, doesn't have such a significant effect on central hemodynamics, but it can have a positive antiproliferative, metabolic and nephroprotective effect. Thereby, the study of SGLT-2 use in patients with amyloid cardiomyopathy with any phenotype of HF compared to placebo is of special interest. Aims: Determination of the possibility of influence of early administration of SGLT-2 inhibitor dapagliflozin on a course of the disease (functional status, clinical and laboratory parameters, systolic and diastolic function of the left and right ventricular, cardiac strain parameters, parameters of target organ functions) in patients with the acute decompensated heart failure (ADHF), regardless of LVEF, against the background of transthyretin amyloid cardiomyopathy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction, Heart Failure With Preserved Ejection Fraction, Heart Failure With Mid Range Ejection Fraction, Amyloid Cardiomyopathy
Keywords
heart failure, amyloidosis, cardiomyopathy, amyloid cardiomyopathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
a single-center, pilot, prospective, randomized, placebo-controlled clinical trial
Masking
Participant
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozine group
Arm Type
Experimental
Arm Description
20 patients diagnosed with heart failure and amyloid cardiomyopathy, regardless of HF phenotype, are planned to be enrolled in the study. Patients with the edematous syndrome are allowed to participate in the study, but the condition of stable hemodynamics must be observed. Regardless of the group, patients will receive standard therapy for ADHF (diuretics and MRA). Patients will not receive beta-blockers/ACE-I/ARNI. In the treatment group the therapy will include the SGLT-2 inhibitor dapagliflozin, which will be prescribed during the first 24 hours after the hospitalization.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
In the control group, patients will be treated with standard diuretic therapy without SGLT-2 inhibitors.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10mg Tab
Intervention Description
10 mg tablets given once daily, per oral use
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
tablet of placebo drug dosed once daily
Primary Outcome Measure Information:
Title
Effect of dapagliflozin on quality of life using Kansas City Cardiomyopathy Questionnaire Summary Score (KCCQ-SC)
Description
Changes in KCCQ score will be assessed
Time Frame
6 months
Title
Effect of Dapagliflozin on 6 Minute Walk Test Distance
Description
Changes in 6MWT score will be assessed
Time Frame
6 months
Title
Effect of dapagliflozin on N-terminal Pro B-type Natriuretic Peptide (NTproBNP)
Description
Changes in concentration of NT-proBNP will be assessed
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Cardiovascular death + number of hospitalizations due to heart failure
Time Frame
6 months
Title
Effect of dapagliflozin on change in echocardiographic parameters
Description
Left ventricular ejection fraction will be assessed
Time Frame
6 months
Title
Effect of dapagliflozin on change in specle-tracking echocardiographic parameters
Description
Global longitudinal strain will be assessed
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females between 18 and 80 years of age HF, confirmed with the increased level of NT-proBNP>300 pg/mL or BNP>100 pg/mL Transthyretin amyloid cardiomyopathy, confirmed with echocardiography and/or contrast-enhanced cardiac MRI Exclusion Criteria: The inability to continue all the activities planned in this study by the patient. The onset of pregnancy. Patient's voluntary withdrawal of consent to participate in a clinical trial at any point during the conduct of the study. Development of intolerable side effects. Administration of disease-modifying treatment of amyloidosis.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Svetlana Nikolaevna Nasonova, PhD
Phone
+79104346858
Email
Dr.Nasonova@mail.ru
Facility Information:
Facility Name
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Svetlana Nikolaevna Nasonova, PhD
Phone
+79104346858
Email
Dr.Nasonova@mail.ru

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Administration of the SGLT-2 Inhibitor Dapagliflozin in the Patients With Amyloid Cardiomyopathy

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