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

The Effect of Correction of Bacterial Overgrowth Syndrome in the Small Intestine on Cardiac Function in Patients with Heart Failure with Preserved Ejection Fraction

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure with Preserved Ejection Fraction; Bacterial Overgrowth Syndrome Small Bowel
• Intervention / Treatment: Drug: Rifaximin; Other: Standard HFpEF treatment

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Konstantin Ivashkin; Phone Number: +7 926 213 58 33; Email: ivashkin_k_v@staff.sechenov.ru
• Study Contact Backup: Name: Elena Bueverova; Phone Number: +7 916 526 6245; Email: bueverova_e_l@staff.sechenov.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Moscow
    • Contact: Elena Bueverova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention group; 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.	Drug: Rifaximin; 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; Other Names: Alfa Normix®; Other: Standard HFpEF treatment; diuretic, including an aldosterone antagonist; sodium-glucose cotransporter-2 inhibitor
Active Comparator: control group; Patients of the control group will receive standart therapy HFpEF Without Rifaximin	Other: Standard HFpEF treatment; diuretic, including an aldosterone antagonist; sodium-glucose cotransporter-2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing the functional class (FC) of chronic heart failure (CHF)	The 6-Minute Walk Distance (6-MVD) The test will be conducted according to the standard procedure in a marked corridor (length 50 meters) in the morning. Each patient needs to walk the maximum possible distance along the corridor at an acceptably fast pace in 6 minutes. Interpretation of the results in relation to the classification of the New York Heart Association Classification: 426- 550 m corresponds to FC I, 301-425 m corresponds to FC II, 151-300 m corresponds to FC III, less than 150 m corresponds to FC IV.	Day 1, day 10, day 40
Change in clinical condition	Clinical Condition Assessment Scale (CCAS) (in the modification of Mareev V.Yu., 2000) This scale includes 10 points (depending on the result, each answer is assigned a certain number of points, which are summed up): shortness of breath (0 - no, 1 - under load, 2 - at rest), weight change over the last week (0 - no, 1 - increased), complaints of irregular heartbeat (0 - no, 1 - there is), the patient's position in bed (0 - horizontally, 1 - with raised headboard (+2 pillows), 2 - plus wakes up from suffocation, 3 - sitting), swollen cervical veins (0 - no, 1 - lying down, 2 - standing), wheezing in the lungs (0 - no, 1 - lower parts (up to 1/3), 2 - up to the shoulder blades (up to 2/3), 3 - over the entire surface of the lungs), the presence of a gallop rhythm (0 - no, 1 - there is), liver (0 - not enlarged, 1 - up to 5 cm, 2 - more than 5 cm), edema (0 - no, 1 - pastosity, 2 - edema, 3 - anasarca), the level of systolic blood pressure (0 - >120, 1 - 100-200, 2 - <100 mmHg). Summary	Day 1, day 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the level of C-reactive protein in blood serum	Venous blood will be taken on an empty stomach at 7-9 am without any special preparation	Day 1, day 40
Changes in serum fibrinogen levels	Venous blood will be taken on an empty stomach at 7-9 am without any special preparation	Day 1, day 40
Changes in serum ferritin levels	Venous blood will be taken on an empty stomach at 7-9 am without any special preparation	Day 1, day 40
Change in the presence of the small intestinal bacterial overgrowth	Hydrogen breathing test with lactulose on Gastro+ Gastrolyzer (EC60) (Bedfont Scientific Ltd., Great Britain, registration number 2010/06253 dated 09/17/2020) in accordance with the North American consensus: the presence of excessive bacterial growth in the small intestine is considered when the hydrogen content in the breath is increased by at least 20 ppm above the initial value for 90 minutes after taking 10 ml of lactulose dissolved in 200 ml of water	Day 2, day 10, day 40
Change in the maximum volume of the left atrium indexed to the body surface area	Transthoracic echocardiography (GE VIVID E95, "GE Vingmed Ultrasound AS", Norway, registration certificate 2016/3871 dated 10/17/2022) will be performed at 10-12 am without any special preparation	Day 1, day 40
Change in the ratio of the maximum rates of early diastolic transmittal blood flow (E) and diastolic elevation of the base of the left ventricle in the early diastole (e') Е/e'	Transthoracic echocardiography (GE VIVID E95, "GE Vingmed Ultrasound AS", Norway, registration certificate 2016/3871 dated 10/17/2022) will be performed at 10-12 am without any special preparation	Day 1, day 40
Change in tricuspid regurgitation	Transthoracic echocardiography (GE VIVID E95, "GE Vingmed Ultrasound AS", Norway, registration certificate 2016/3871 dated 10/17/2022) will be performed at 10-12 am without any special preparation	Day 1, day 40

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Vladimir Ivashkin, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: September 9, 2024
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Diastolic dysfunction; Chronic heart failure with preserved ejection fraction; The gut-heart axis; Small intestinal bacterial overgrowth syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Metabolic Diseases; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Malabsorption Syndromes; Heart Failure; Syndrome; Blind Loop Syndrome; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents; Rifaximin
• Other Study ID Numbers: VI27478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The disclosure of data is not allowed by the Local Ethics Committee of the I.M. Sechenov First Moscow State Medical University (Sechenov University).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No