Treating the gut flora to improve heart failure

Phase 1

• Conditions: Heart failure; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-000192-27-NO
• Lead Sponsor: Oslo University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-04
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• 18 = and <75 years of age
• Clinical or symptomatic evidence of HF, in NYHA class II-III and LVEF
< 40%
• Signed informed consent and expected cooperation of the patients for
the treatment and follow-up must be obtained and documented
according to ICH GCP, and national/local regulations
• Patients should be stabilized on state-of-art HF medication for more
than 3 months prior to inclusion
• Acceptable acoustic windows for echocardiographic assessment
All of the following conditions must apply to the prospective patient at
screening prior to receiving study agent (e.g.):
• Must be at least 18 years of age, and less than 75.
• Have heart failure in New York Heart Association class II or III
• Echocardiographically verified LVEF < 40 %.
• On optimal treatment for at least 3 months
• Must have lab values as the following:
• Hemoglobin above 10 g/l
• eGFR above 30 ml/min
• ALT < 150 units/l
• Signed informed consent and expected cooperation of the patients for
the treatment and follow up must be obtained and documented
according to ICH GCP, and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

• Treatment with antibiotics or probiotics within the last 12 weeks
• History of hypersensitivity to Rifaximin or other Rifamycin derived
antimicrobial agents, or any of the components of Xifaxan
(http://www.legemiddelverket.no/_layouts/Preparatomtaler/Spc/11-
8645.pdf?id=05122013165930).
• History of hypersensitivity to S. boulardii, yeast, or any of the
components of Precosa
(http://www.legemiddelverket.no/_layouts/Preparatomtaler/Spc/1994
-02012.pdf?id=03042014142345).
• Polypharmacia with increased risk for interactions. i.e. patient with
an extensive medication lists (e.g. 10 drugs or more) which may
influence with the patient safety or compromise the study results
• Malignancy of any cause, excluding basal cell carcinoma of the skin
• Acute coronary syndrome over the last 12 weeks
• Severly impaired kidney function (i.e., estimated glomerulus filtration
rate < 30 ml/minute/1.73 m2)
• Impaired liver function (Alanine aminotransferase > 150 U/l) or
decompensated liver cirrhosis classified as Child–Pugh B or C.
• On-going infection, including GI infection
• Inflammatory bowel disease
• Bowel obstruction
• Active myocarditis, including Chagas disease
• Severe primary valvular heart disease
• Atrial fibrillation with ventricular frequency > 100/min
• Any other, severe comorbid disease that must be expected to severely
reduce the efficacy of the interventional products, survival or compliance
• Treatment with immunosuppressive drugs
• Treatment with rifamycins other than Rifaximin
• Central venous catheter
• Pregnancy or planned pregnancy
• Nursing
• Poor compliance
• Any reason why, in the opinion of the investigator, the patient should
not participate.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: N/A;Timepoint(s) of evaluation of this end point: Baseline and after 3 months intervention;Main Objective: The main objective of the study is to investigate the gut microbiota as a<br>potential therapeutic target in HF:<br>• By characterizing the composition of gut microbiota in HF patients<br>compared to healthy controls.<br>• By characterizing the effect of antibiotics and probiotics on the gut<br>microbiota and systemic inflammatory and metabolic markers in HF<br>patients.<br>• By characterizing the effect of antibiotics and probiotics on cardiac<br>function in HF patients.;Primary end point(s): The primary end point of this study is baseline-adjusted LVEF as<br>measured by echocardiography after 3 months of intervention.The trial<br>is powered to show a 5 per cent point increase in either intervention arm<br>compared to the control group (the statistical null-hypothesis being that<br>there is no difference between any of the two intervention arms and the<br>control arm).

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Baseline and after 3 months intervention;Secondary end point(s): The secondary endpoints will assess differences between either of the<br>treatment arms an the control group at the end-of study, as well as at<br>the pre-defined follow-up time points, regarding (i) the gut microbiota<br>composition, (ii) microbiota-related metabolites, (iii) extended<br>parameters on cardiac function in addition to LVEF, (iv) inflammatory<br>and anti-inflammatory mediators in plasma, serum, peripheral blood<br>mononuclear cells (PBMC) and whole blood, (v) health-related quality of<br>life, (vi) functional capacity and (vii) safety