Randomized Double-blind Controlled Clinical Study of SGLT-2i Combined With Probiotic Preparations in Elderly Patients With HFpEF

Обзор

HFpEF has a high incidence and lacks effective therapy, and its onset is closely related to systemic inflammation and intestinal dysbacteriosis.SGLT-2i exerts its effects by diuresis, anti-inflammatory and improving energy metabolism, whereas probiotics modulate intestinal flora, reduce inflammatory markers, and regulate immune responses.The combination of the two drugs is not only expected to exert synergistic therapeutic potential, but may also reduce the risk of sarcopenia associated with SGLT-2i weight loss.This study aims to combine henagliflozin and a probiotic preparation on the basis of standard anti-heart-failure therapy, and to observe their effects on cardiac and renal function, intestinal barrier function, quality of life, and exercise tolerance in elderly patients with HFpEF, while exploring the underlying mechanisms, so as to provide new data and therapeutic strategies for the treatment of elderly HFpEF patients.

Вмешательства

• Препарат Henggliflozin Combined with Probiotics
  Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + clostridial enterococcus triple live tablet (400mg, 3 times/day) orally, for 12 weeks.
• Препарат Henggliflozin
  Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + placebo (400mg, 3 times/day) orally, for 12 weeks.
• Препарат double placebo
  Primary anti-HF therapy +Two types of placebo tablets orally, for 12 weeks.

Первичные конечные точки

• Kansas City Cardiomyopathy Questionnaire (KCCQ)scale score [Срок оценки: Baseline, Week 4, Week 8,Week 12]

Вторичные конечные точки (12)

• NYHA functional classification [Срок оценки: Baseline, Week 4, Week 8,Week 12]
• 6-Minute Walk Test (6MWT) Distance [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) Level [Срок оценки: Baseline, Week 4, Week 8,Week 12]
• Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total Score [Срок оценки: Baseline, Week 4, Week 8,Week 12]
• Serum Inflammatory Biomarkers (NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1) [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Gut Microbiota Composition and Diversity [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Frailty Status Using the Fried Frailty Phenotype Criteria [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Nutritional Status Using the Mini Nutritional Assessment (MNA) Scale [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Basic Activities of Daily Living (BADL) Scale Score [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• SARC-F Scale Score [Срок оценки: Baseline, Week 4, Week 8, Week 12]
• Fecal Short Chain Fatty Acids (SCFAs) [Срок оценки: Baseline, Week 12]
• Serum Trimethylamine-N Oxide (TMAO) [Срок оценки: Baseline, Week 12]

Критерии участия

Критерии включения

• 1\. Age over 60 years; 2.Relevant investigations within 6 months meet diagnostic criteria for HFpEF:

• epidemiologic and population characteristics of patients with HFpEF;
• presence of symptoms and/or signs of heart failure;
• Cardiac imaging suggests LVEF >=50%;
• BNP>=35pg/ml and (or) NT-pro BNP>=125pg/ml in sinus rhythm, and BNP>=105pg/ml and (or) NT-pro BNP>=365pg/ml in atrial fibrillation;
• at least one of the following conditions is met: 1) LVMI>=115 g/m\^2(male)or 95 g/m\^2(female); 2) LAVI>34 ml/m\^2; 3) Relative wall thickness>0.42;or left ventricular free wall thickness>12mm; 4) E/e'>=14; 5) Ventricular septal e'<7cm/s, or lateral wall e'<10cm/s, or mean e'<8cm/s; 6) Tricuspid regurgitant velocity>2.8m/s, or pulmonary artery systolic pressure>35mmHg; 3.NYHA class II to III for cardiac function; 4. not taking SGLT-2 inhibitors within 6 months before enrollment; 5. no probiotic preparations taken within 3 months before enrollment; 6. The current anti-HF Therapeutic Regimen is well tolerated by patients and is stable for at least 1 month; 7. Currently stable HF with no acute exacerbations; 8. Cognitive Functioning is basically normal with comprehensible assessment scale content; 9. possess basic behavioral ability, being able to perform daily activities independently or with the help of accessory aids; 10. Understand the purpose of the Clinical Study, voluntarily participate and sign informed consent.

Критерии исключения

• 1\. the patient's symptoms are due to noncardiac disease; 2. In those with contraindications to Henggliflozin:

• those who are allergic to henggliflozin;
• severe renal impairment (eGFR<30ml/min/1.73m\^2), end-stage renal disease, or those requiring dialysis; 3. In those with contraindications to probiotics:

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• Patients with severe impairment of the intestinal barrier associated with sepsis, active massive bleeding from the digestive tract, perforation, and other causes.
• those with current diagnosis of fulminant colitis or toxic megacolon.
• Enteral feeding that cannot tolerate 50% caloric requirement due to severe diarrhea, significant fibrous intestinal stenosis, severe gastrointestinal bleeding, high-flow intestinal fistula, etc.
• Patients with congenital or acquired immune deficiency.
• Those recently treated with high-risk immunosuppression or cytotoxic drugs: e.g., continued use of rituximab, doxorubicin, or a medium-to high-dose steroid hormone (20 mg/d prednisone or higher) for more than 4 weeks.
• Severe immunosuppression: Neutrophils <1 500/mm\^3. 4. had a myocardial infarction within 6 months before enrollment, had a coronary artery bypass graft procedure, or had any event that could reduce LVEF (unless an LVEF >=50%) confirmed; 5. valve replacement surgery within 6 months before enrollment; 6.Poor blood pressure control (SBP>=180mmHg or DBP>=100 mmHg); 7. Current acute decompensated heart failure requires treatment; 8. Resting heart rate exceeding 120 beats/min, or complicated by malignant Arrhythmia; 9. Significant coronary artery lesions require PCI revascularization; 10. Severe renal insufficiency (blood creatinine, Cr >442μmol/L) or receiving dialysis treatment; 11. Patients with urinary tract infection at entry; symptoms and signs of urinary tract infection, such as urinary tract irritation signs (frequent urination, painful urination, urgency), pain and tenderness above the pubic bone, fever, pain or percussion pain in the waist, etc., and urine bacterial culture colony counts >=105/ml; 12. currently having a malignancy that requires treatment; 13. Current concurrent acute disease or acute exacerbation of chronic disease; 14.Participated in other interventional investigators within 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Air Force Medical University — Xi’an

Идентификаторы

NCT: NCT07687212 · KY20262160

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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