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Rifaximin and Cardiac Function in Patients with Heart Failure with Preserved Ejection Fraction (SIBO-HFpEF)

I

I.M. Sechenov First Moscow State Medical University

Status

Enrolling

Conditions

Heart Failure with Preserved Ejection Fraction
Bacterial Overgrowth Syndrome Small Bowel

Treatments

Drug: Rifaximin
Other: Standard HFpEF treatment

Study type

Interventional

Funder types

Other

Identifiers

NCT06652087
VI27478

Details and patient eligibility

About

Single-center, double-blind, randomized, controlled intervention study of the effect of correction of bacterial overgrowth syndrome in the small intestine (SIBO) on cardiac function in patients with heart failure with preserved ejection fraction (HFpEF) (SIBO-HFpEF). The aim of the study is to evaluate the efficacy and safety of rifaximin in patients with HFpEF and SIBO.

Full description

The proportion of patients with obvious symptoms of chronic heart failure with preserved ejection fraction (HFpEF) is more than 50%, and mortality is comparable to that of patients with low ejection fraction. The lack of evidence regarding therapeutic possibilities for improving the prognosis leads to the search for new treatment regimens. Systemic low-grade inflammation is recognized as the fundamental pathophysiological mechanism of HFpEF. On the one hand, it is caused by obesity, which is the background for the comorbidity of these patients. On the other hand, chronic sluggish systemic inflammation in combination with changes in the composition and metabolic activity of the gut microbiota, dysfunction of the intestinal barrier explains the role of the gut-heart axis in the pathogenesis of HFpEF. There is evidence that small intestinal bacterial overgrowth syndrome (SIBO) is an independent risk factor for re-hospitalization and cardiovascular death among all patients with heart failure. SIBO and its correction in patients with HFpEF have not been sufficiently studied.

Forty patients with HFpEF with a body mass index of more than 25 kg/m2 and a positive SIBO test will be randomly assigned in a ratio of 1:1 to the experimental (rifaximin) and control groups. To detect SIBO, a hydrogen breathing test with lactulose (Duphalac®, Abbott Biologicals B.V., the Netherlands, registration number N011717/02 dated 02/04/2010) will be performed on a medical device "Respiratory hydrogen Gastro+ Gastrolyzer®(EC60) with accessories" (Bedfont Scientific Ltd., Great Britain, registration number 2010/06253 dated 09/17/2020). For 2 hours, every 15 minutes, the patient will be asked to take a deep breath, hold his breath for 10-15 seconds and exhale into a special device for measuring the concentration of hydrogen in the exhaled air. Interpretation of a positive result (threshold of increase from the zero point): ≥20 ppm. Patients in the experimental group (SIBO positive test) will be prescribed rifaximin (Alfa Normix®, Alfa Wassermann S.P.A., Italy, registration number LS-001993, 08/31/2010) in standard doses of 200 mg 3 times a day for 7 days. Patients from the control group (positive SIBO test) will not receive rifaximin. All patients will also receive standard HFpEF treatment (diuretic, including an aldosterone antagonist; sodium-glucose cotransporter-2 inhibitor). Patients will be blinded. A control breath test with lactulose will be performed after completion of rifaximin intake and one month after discharge from the hospital. Markers of systemic inflammation in the blood (levels of C-reactive protein, fibrinogen and ferritin) and parameters of diastolic dysfunction (transthoracic echocardiography) will also be evaluated. After the end of the study, an analysis of the effect of adding rifaximin to the standard treatment of CHF compared with the control group will be carried out.Patients from the control group (with a positive SIBO test result) will not receive rifaximin. All patients will also receive standard treatment for HFRS (diuretics, including an aldosterone antagonist; a sodium-glucose cotransporter-2 inhibitor). Patients will be blinded. A control breath test with lactulose will be performed after completion of rifaximin and one month after discharge from the hospital. Markers of systemic inflammation in the blood (levels of C-reactive protein, fibrinogen and ferritin) and parameters of diastolic dysfunction (transthoracic echocardiography) will also be evaluated. After the end of the study, the effect of adding rifaximin to the standard treatment of CHF will be analyzed compared with the control group. Researchers suggest that rifaximin reduces the level of markers of systemic inflammation, reduces the severity of diastolic dysfunction, is effective in SIBR in patients with HF and BMI≥25 kg/m2, improves their quality of life and prognosis. Patients from the control group (with a positive SIBO test result) will not receive rifaximin. All patients will also receive standard treatment for HFRS (diuretics, including an aldosterone antagonist; a sodium-glucose cotransporter-2 inhibitor). Patients will be blinded. A control breath test with lactulose will be performed after completion of rifaximin and one month after discharge from the hospital. Markers of systemic inflammation in the blood (levels of C-reactive protein, fibrinogen and ferritin) and parameters of diastolic dysfunction (transthoracic echocardiography) will also be evaluated. After the end of the study, the effect of adding rifaximin to the standard treatment of CHF will be analyzed compared with the control group. Researchers suggest that rifaximin reduces the level of markers of systemic inflammation, reduces the severity of diastolic dysfunction, is effective in SIBR in patients with HF and BMI≥25 kg/m2, improves their quality of life and prognosis.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. availability of written informed consent of the patient to participate in the study
  2. adult aged ≥18≤80 years' old
  3. body mass index ≥25 kg/m2
  4. diagnosed with HFpEF: 1) symptoms and/or signs of heart failure; 2) left ventricular ejection fraction ≥50%; 3) increased levels of natriuretic peptides (NTproBNP≥125 pg/mL); 4) at least one additional criterion: relevant structural heart disease (hypertrophy of the left ventricle (LVH) and/or enlargement of the left atrium (LAE) or diastolic dysfunction

Exclusion criteria

  1. refusal of the patient from further participation in the study
  2. identification of any disease or condition specified in the criteria for non-inclusion and the development of a severe pathological condition in which patient monitoring becomes poorly implemented and the presence of which may make it difficult to interpret the data (gastrointestinal bleeding, myocardial infarction, etc.)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

40 participants in 2 patient groups

intervention group
Experimental group
Description:
Patients of the experimental group will receive standart therapy HFpEF and rifaximin (Alfa Normix®, Alfa Wassermann S.P.A., Italy, registration number LS-001993, 08/31/2010) at a dose of 200 mg 3 times a day for 7 days.
Treatment:
Other: Standard HFpEF treatment
Drug: Rifaximin
control group
Active Comparator group
Description:
Patients of the control group will receive standart therapy HFpEF Without Rifaximin
Treatment:
Other: Standard HFpEF treatment

Trial contacts and locations

1

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Central trial contact

Konstantin Ivashkin; Elena Bueverova

Data sourced from clinicaltrials.gov

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