Clinical trial NCT04778787: Sodium-glucose Cotransporter Type 2 Inhibitors for Acute Cardiorenal Syndrome Prevention
Official title: Impact of Sodium-glucose Cotransporter Type 2 Inhibitors on the Course of Cardiorenal Syndrome in Acute Decompensation of Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Congestive Heart Failure
Keywords: heart failure
decompensation
gliflozins
kidneys
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 370
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: The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on the parameters of renal function in acute decompensation of chronic heart failure (ADHF) compared to standard therapy will be analyzed. Based on the dynamics of the clinical condition, the duration of hospitalization, and blood biochemical parameters (creatinine, urea, uric acid, potassium, sodium, N-terminal pro-brain natriuretic peptide - NT-proBNP) conclusions will be drawn about the possibility of using SGLT2i in this group of patients.

Detailed description: This is a randomized multicenter prospective clinical trial involving patients over 18 years of age who were hospitalized due to decompensation of chronic heart failure (CHF).

The aim of the study is to evaluate the effect of SGLT2i on renal function in the treatment of decompensation of chronic heart failure compared to standard therapy.

The study is planned to include 370 patients with decompensated chronic heart failure. The study will be conducted in Сity clinical hospital number 7, University clinical hospital number 1.

Patients will be screened in the first 24 hours from the moment of hospitalization, inclusion and exclusion criteria will be applied. The ADHF diagnosis was made based on 1) presence of congestion (based on the presence of dyspnoea and at least two of the following:congestion on chest X-ray in straight and side projections with radiation load 0,1 mSv (СombiDiagnost R90, №2017/6644), rales on chest auscultation, peripheral edema, swelling of the cervical veins, hepatomegaly, ascites, hepatojugular reflux) 2) the need for intravenous administration of loop diuretics.

The diagnosis will be confirmed by echocardiography (ECHO) (Ge Logic F6; №9451\\61287) to assess systolic (a decrease in LV ejection fraction (LVEF) \<50%) and diastolic dysfunction (ratio of early diastolic transmitral E flow to the average early diastolic velocity of the fibrous ring e´ \>14; left atrial volume index (LAVI) \>34 ml/m2; the maximum speed of tricuspid regurgitation \>2.8 m/s ( American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) recommendations)\[11\]) and the presence of an enlarged, non-collapsing on inspiration inferior vena cava (IVC).

Intravenous administration of 40 mg of furosemide (lasix; 10 mg / ml; N014865/02) is allowed no later than in the first 24 hours from the moment of admission (provided that the patient has not previously received regular loop diuretics). If prior to this hospitalization, regular therapy with loop diuretics was carried out, the daily dose should be increased by more than 2 times with the transition to intravenous administration.

During the first visit, patients who meet the inclusion criteria will be randomized by the random number table method. Participants will be divided into two groups, the main group will include patients receiving dapagliflozin (Forxiga; MP-002596) at a dose of 10 mg / day per os in addition to the current therapy. The comparison group will be patients receiving standard therapy (loop diuretics, vasodilators, digoxin, inotropic agents, vasopressors).

During the second visit (48 hours after randomization), the researcher will assess the clinical condition (blood pressure, heart rate, respiratory rate, auscultation, edema dynamics), biochemical and general blood analysis, and patient weighing in both groups of patients. Accounting for how the patient excretes fluid will be made by the research doctor by weighing in the morning on an empty stomach and calculating the volume of diuresis.

During the third visit (on the day of discharge ), the researcher will assess the clinical condition (blood pressure, heart rate, respiratory rate, auscultation, edema dynamics), biochemical and general blood analysis, and patient weighing in both groups of patients.

The criterion for acute renal injury will be an increase in serum creatinine by 0.3 mg / dl or more for 48 hours (Kidney Disease: Improving Global Outcomes (KDIGO) criteria). The criteria for refractoriness to diuretic therapy will be the need to increase the daily dose of loop diuretics by more than 2 times compared to the initial one, or the need to add another class of diuretic drugs to the therapy. (Muthiah Vaduganathan et al. Unsolved challenges in diuretic therapy for acute heart failure: a focus on diuretic response.Expert Review of Cardiovascular Therapy/ Volume 13, 2015 -Issue 10. Pages

1075-1078). The initial dose will be the daily dose of loop diuretics used on the first day of hospitalization.

In order to find out whether there were repeated hospitalizations or deaths of patients within 30 days, the study participants will be called on the 30th day after discharge.

The reliability of the differences in the groups will be determined by the Man-Whitney criterion, the differences will be considered statistically significant at p\<0.05. Statistical processing of the obtained data will be carried out using the Statistical Package for the Social Sciences program version 9.0.

The study can be classified as a study of average accuracy. The significance level of 0.05 will be used as the limit of the statistical significance of the results, then according to the method of K. A. Otdelnova, the sample size of the dissertation research should be 100 observation units. The research capacity will be 80%.

Eligibility criteria: Inclusion criteria

1. Diagnosed ADHF (based on 1) presence of congestion (based on the presence of dyspnoea and at least two of the following:congestion on chest X-ray, rales on chest auscultation, peripheral edema, swelling of the cervical veins, hepatomegaly, ascites, hepatojugular reflux) 2) the need for intravenous administration of loop diuretics.

The diagnosis will be confirmed by echocardiography (ECHO) to assess systolic (a decrease in LV ejection fraction (LVEF) \<50%) and diastolic dysfunction (ratio of early diastolic transmitral E flow to the average early diastolic velocity of the fibrous ring e´ \>14; left atrial volume index (LAVI) \>34 ml/m2; the maximum speed of tricuspid regurgitation \>2.8 m/s ( American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) recommendations)\[11\]) and the presence of an enlarged, non-collapsing on inspiration inferior vena cava (IVC)) 2. The need for intravenous administration of loop diuretics on admission 3. Age over 18 years Patients were included after signing an informed consent Exclusion criteria

1. Cardiogenic shock (systolic blood pressure \<90 mm Hg; signs of hypoperfusion (altered mental status, cold skin, diuresis \<30 ml / hour, blood lactate level \>2.0 mmol / l).
2. Urinary tract infection
3. Type 1 diabetes mellitus (DM1), episodes of diabetic ketoacidosis or hypoglycemia
4. Prior use of drugs from the SGLT2i group, taken regularly within 4 weeks
5. GFR\<30 ml / min / 1.73 m2 (CKD-EPI).
6. Individual SGLT2i intolerance
7. Child-Pugh class C liver failure
8. Mental illness (inability to sign an informed consent, lack of understanding of possible consequences)
9. Pregnancy or breastfeeding
10. Refusal to sign an informed consent

Primary outcomes:
measure: death due to heart failure
timeFrame: through study completion, an average of 5 days
Secondary outcomes:
measure: deterioration of renal function (increase in blood creatinine by 0.3 mg / dl within 48 hours)
timeFrame: through study completion, an average of 5 days
measure: development of resistance to diuretics
timeFrame: through study completion, an average of 5 days
measure: re-hospitalization about decompensation of chronic heart failure within 30 days after discharge from the hospital
timeFrame: up to 30 days
Other outcomes:
measure: weight loss during hospitalization
timeFrame: through study completion, an average of 5 days
measure: admission to the intensive care unit due to worsening heart failure during the current hospitalization
timeFrame: through study completion, an average of 5 days
Locations:
city: Moscow
country: Russian Federation
facility: University Clinical Hospital number 1
city: Moscow
country: Russian Federation
facility: Сity Сlinical Нospital number 7
Study officials:
References:
citation: Vaduganathan M, Kumar V, Voors AA, Butler J. Unsolved challenges in diuretic therapy for acute heart failure: a focus on diuretic response. Expert Rev Cardiovasc Ther. 2015 Oct;13(10):1075-8. doi: 10.1586/14779072.2015.1087313. Epub 2015 Sep 10.