Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05795400 |
| Other study ID # |
20230120 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
June 2025 |
Study information
| Verified date |
March 2023 |
| Source |
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation |
| Contact |
Svetlana Nikolaevna Nasonova, PhD |
| Phone |
+79104346858 |
| Email |
Dr.Nasonova[@]mail.ru |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
