Clinical trial NCT06055452: Effects of SGLT2 Inhibitors in Pre-heart Failure Populations With Hypertension
Official title: Effects and Mechanism of SGLT2 Inhibitors in Pre-heart Failure Populations With Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pre-Heart Failure
Hypertension
Keywords: Pre-Heart Failure
Hypertension
Randomized controlled trial
Empagliflozin
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2023-09-26
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this multicenter, randomized, placebo-controlled trial in pre-heat failure patients with hypertension and without diabetes, we will enroll 120 eligible patients to randomized to receive placebo or engagliflozin (10mg/d) for follow them for 6 months. The primary endpoint is the left atrial volume index, which reflects left ventricular diastolic function. We sought to comprehensively evaluate the effect of engagliflozin on the structure and function and explore its underlying mechanisms.

Detailed description: Hypertension is the leading risk factor of heart failure with preserved heart failure. The overall control rate is about 16% in China. Given the large amounts of hypertensive patients at pre-heart failure (stage B), it's critical to explore the effect of additional cardioprotective medication in addition to well-controlled blood pressure. Sodium-glucose cotransporter-2 inhibitors (engagliflozin) have been shown to improve cardiac function or prognosis in patients with diabetes or heart failure. However, whether it has a cardioprotective effect on hypertensive patients with pre-heart failure and without diabetes remains unknown. We will conduct a multicenter, randomized, placebo-controlled trial in pre-heat failure patients with hypertension and without diabetes. We will enroll 120 eligible patients randomized to receive a placebo or engagliflozin (10mg/d) for follow them for 6 months. The primary endpoint is the left atrial volume index, which reflects left ventricular diastolic function. The secondary endpoints include echocardiography or magnetic resonance imaging to measure structural and functional parameters, blood pressure, glucose, and blood biomarkers of inflammation and fibrosis. We sought to comprehensively evaluate the effect of empagliflozin on the structure and function and explore the underlying mechanisms to provide insights and evidence for the prevention of heart failure in hypertensive patients.

Eligibility criteria: Inclusion Criteria:

• Meeting all the following criteria:

1. Aged 40 and above; less than 75 years.
2. Hypertensive patients currently taking at least one antihypertensive medication as recommended by guidelines, and blood pressure is within the target range (\<140/90 mmHg).
3. The left atrial volume index measured by transthoracic echocardiography exceeds 34 mL/m², or the ratio of the average E/e' \>9 and left atrial volume index \>= 29 mL/m² measured by transthoracic echocardiography.
4. Signing an informed consent form.

Exclusion Criteria:

* • Exclusion criteria include any of the following conditions:

  1. History of diabetes.
  2. History of heart failure.
  3. History of coronary artery disease.
  4. Left ventricular systolic dysfunction, defined as LVEF \< 50%.
  5. Systolic blood pressure \< 100 mmHg.
  6. A history of arrhythmias such as atrial fibrillation, atrial flutter, frequent atrial premature contractions, and frequent ventricular premature contractions may impact the structural and functional aspects of the heart.
  7. Moderate and above valvular heart disease.
  8. Severe obstructive disease of the left ventricular outflow tract, including aortic valve stenosis.
  9. Visited within the past 1 month due to Genitourinary tract infection.
  10. Chronic kidney disease or estimated Glomerular Filtration Rate (eGFR) \< 45 ml/min/1.73m².
  11. Alanine aminotransferase or aspartate aminotransferase levels \> 3 times the upper limit of normal.
  12. Contraindications to taking SGLT2 inhibitors.
  13. Currently taking SGLT2 inhibitors, SGLT-1/2 inhibitors, or other antihyperglycemic medications (including metformin, glucagon-like peptide-1 receptor agonists, etc.).
  14. Pregnancy or planning pregnant, or currently breastfeeding.
  15. Malignant tumors or other severe illnesses with a life expectancy of less than 3 years.
  16. History of alcohol abuse or substance abuse within the past year.
  17. Mental disorders or communication barriers, cognitive impairments, or other severe illnesses that may affect participation in the study.
  18. Participation in or currently participating in other clinical trials within the last 3 months.
  19. Known poor compliance with study follow-up or study drug.
  20. Any condition or contraindication that makes a person intolerant to magnetic resonance imaging (MRI) or contraindicates MRI examination, such as the presence of implanted intracranial aneurysm clips, cardiac pacemakers or defibrillators, insulin pumps, etc.

Primary outcomes:
measure: Change of left atrial volume index
timeFrame: 6 months
Secondary outcomes:
measure: Change of cardiac structure and functional
timeFrame: 6 months
measure: Biomarkers
timeFrame: 6 months
measure: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Shenzhen
country: China
facility: Fuwai Hospital Chinese Academy of Medial Sciences, Shenzhen
state: Guangdong
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Xin Zheng, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: