Enhanced Nutritional Optimization in LVAD Trial

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess whether a peri-operative intervention with nutritional immune modulating intervention (Ensure Surgery Immunonutrition shake) has beneficial effects on the complex interplay between gut microbiome, systemic inflammation and malnutrition that is commonly present in advanced heart failure and the adverse events associated with left ventricular assist device (LVAD) placement in hospitalized advanced heart failure patients awaiting LVAD implantation. The main questions it aims to answer are: Will pre-surgical supplementation with Ensure Surgery affect gut microbial composition and levels of inflammation among heart failure patients undergoing LVAD implantation? Will pre-surgical supplementation with Ensure Surgery affect post-surgical morbidity (e.g., infections, intensive care unit length of stay (LOS)) and mortality? Participants will be evaluated for malnutrition and will be given Ensure Surgery Immunonutrition shake to drink in the days preceding their LVAD surgery. Blood and stool samples will be collected at prespecified timepoints before and after surgery. Researchers will compare malnourished participants drinking Ensure Surgery 3/day with well-nourished participants randomized to drink either 1/day or 3/day to see if any of the above supplementation strategies change the gut microbial composition, levels of inflammation, and post-surgical morbidity and mortality.

Detailed Description
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Heart failure (HF) has an estimated prevalence of >37.7 million individuals globally. In the US alone, which is projected to increase by 46% between the years 2012 and 2030. Despite significant advances in HF medical and device therapies, patient prognosis after their first HF hospital admission is poor, with a <50% survival rate at five years and significant proportion of patients progressing from chronic stable disease to advanced HF state. Once advanced HF ensues, LVADs are one of the two main treatment modalities that can meaningfully improve survival in this patient population. Chronic systemic inflammation is commonly observed in HF and is believed to be directly related to its pathogenesis. Recently, perturbations in the gut microbiota known as gut dysbiosis and impairment of gut mucosal barriers, facilitating entry of endotoxins and gut metabolites into the circulation, have also been observed in HF patients. Elevated levels of circulating endotoxins and bacterial bi-products enhance systemic inflammation, thereby contributing to progression of HF to more advanced disease state. Gut microbial perturbations may also alter enterocyte structure and function resulting in gastrointestinal dysmotility, nutrient malabsorption and eventually malnutrition. Malnutrition is frequent in HF (as high as 62%), is associated with higher rates of mortality, hospital readmissions and an increased risk of adverse early postoperative outcomes. Infections are the most common complications following LVAD, affecting >50% of HF patients, contributing significantly to postoperative mortality, increased length-of stay (LOS) and hospital readmissions. The pre-operative period may represent an attractive time window in which to optimize HF patients, correct deficiencies, and enhance immune defense mechanisms before surgery. This period allows to act upon modifiable risk factors, such as the nutritional status, and potentially lower the risk of postoperative complications. However, the literature on perioperative optimization in HF comes mainly from anesthesiology and focuses on intra- and immediate postoperative management, when it may be too late to intervene and alter the outcome. Interestingly, guidelines on the nutritional evaluation and management of patients prior to non-cardiac surgery are available, but very limited literature is published concerning cardiac surgery, and no data exists with respect to LVAD surgery. The investigators plan to evaluation of the impact of preoperative nutrition intervention.

Official Title
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Enhanced Nutritional Optimization in LVAD (ENOL) Trial

Conditions
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Heart Failure, Gut Microbiome, Nutritional Deficiency

Intervention / Treatment
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* Dietary Supplement: Ensure Surgery Immunonutrition shake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 years hospitalized undergoing LVAD therapy (enrolled at time of acceptance) Exclusion Criteria: intubated congenital heart disease infiltrative cardiomyopathy unable to tolerate oral nutrition surgery expected in <5 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three parallel comparison groups will be created based on assessment of nutritional status and randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Not malnourished) - 3 products per day<br>Patients assessed as well-nourished based on AND-ASPEN criteria and randomized to receive 3 Ensure Surgery Immunonutrition shake per day during the days from consent to LVAD implantation. | Dietary Supplement: Ensure Surgery Immunonutrition shake<br>* Nutrition shake to support immune health and recovery from surgery.<br>|
| Experimental: Group 1 (Not malnourished) - 1 product per day<br>Patients assessed as well-nourished based on AND-ASPEN criteria and randomized to receive 1 Ensure Surgery Immunonutrition shake per day during the days from consent to LVAD implantation. | Dietary Supplement: Ensure Surgery Immunonutrition shake<br>* Nutrition shake to support immune health and recovery from surgery.<br>|
| Experimental: Group 2 (at risk/malnourished)<br>Patients assessed as at risk for malnourishment or malnourished based on AND-ASPEN criteria automatically assigned to receive 3 Ensure Surgery Immunonutrition shake per day during the days from consent to LVAD implantation. | Dietary Supplement: Ensure Surgery Immunonutrition shake<br>* Nutrition shake to support immune health and recovery from surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alpha Diversity (Baseline and Day 5) | Change in alpha diversity (a measure of microbiome diversity applicable to a single sample) in collected stool samples. | Baseline and Day 5 | 
| Change in Alpha Diversity (Baseline and Pre-VAD) | Change in alpha diversity (a measure of microbiome diversity applicable to a single sample) in collected stool samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Alpha Diversity (Baseline and Discharge) | Change in alpha diversity (a measure of microbiome diversity applicable to a single sample) in collected stool samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Alpha Diversity (Baseline and Post-Discharge Follow-up) | Change in alpha diversity (a measure of microbiome diversity applicable to a single sample) in collected stool samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in Microbial Gene Count (Baseline and Day 5) | Change in microbial gene count as measured in stool samples. | Baseline and Day 5 | 
| Change in Microbial Gene Count (Baseline and Pre-VAD) | Change in microbial gene count as measured in stool samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Microbial Gene Count (Baseline and Discharge) | Change in microbial gene count as measured in stool samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Microbial Gene Count (Baseline and Post-Discharge Follow-up) | Change in microbial gene count as measured in stool samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in C-Reactive Protein (CRP) (Baseline and Day 5) | Change in biomarker CRP as measured in blood samples. | Baseline and Day 5 | 
| Change in C-Reactive Protein (CRP) (Baseline and Pre-VAD) | Change in biomarker CRP as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in C-Reactive Protein (CRP) (Baseline and Discharge) | Change in biomarker CRP as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in C-Reactive Protein (CRP) (Baseline and Post-Discharge Follow-up) | Change in biomarker CRP as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in N-terminal (NT)-pro hormone BNP (NT-proBNP) (Baseline and Day 5) | Change in biomarker NT-proBNP as measured in blood samples. | Baseline and Day 5 | 
| Change in N-terminal (NT)-pro hormone BNP (NT-proBNP) (Baseline and Pre-VAD) | Change in biomarker NT-proBNP as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in N-terminal (NT)-pro hormone BNP (NT-proBNP) (Baseline and Discharge) | Change in biomarker NT-proBNP as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in N-terminal (NT)-pro hormone BNP (NT-proBNP) (Baseline and Post-Discharge Follow-up) | Change in biomarker NT-proBNP as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in lipopolysaccharide (LPS) (Baseline and Day 5) | Change in biomarker LPS as measured in blood samples. | Baseline and Day 5 | 
| Change in lipopolysaccharide (LPS) (Baseline and Pre-VAD) | Change in biomarker LPS as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in lipopolysaccharide (LPS) (Baseline and Discharge) | Change in biomarker LPS as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in lipopolysaccharide (LPS) (Baseline and Post-Discharge Follow-up) | Change in biomarker LPS as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in Tumor Necrosis Factor (TNF) (Baseline and Day 5) | Change in biomarker TNF as measured in blood samples. | Baseline and Day 5 | 
| Change in Tumor Necrosis Factor (TNF) (Baseline and Pre-VAD) | Change in biomarker TNF as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Tumor Necrosis Factor (TNF) (Baseline and Discharge) | Change in biomarker TNF as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Tumor Necrosis Factor (TNF) (Baseline and Post-Discharge Follow-up) | Change in biomarker TNF as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in Interleukin 6 (IL-6) (Baseline and Day 5) | Change in biomarker IL-6 as measured in blood samples. | Baseline and Day 5 | 
| Change in Interleukin 6 (IL-6) (Baseline and Pre-VAD) | Change in biomarker IL-6 as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Interleukin 6 (IL-6) (Baseline and Discharge) | Change in biomarker IL-6 as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Interleukin 6 (IL-6) (Baseline and Post-Discharge Follow-up) | Change in biomarker IL-6 as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in Interleukin 10 (IL-10) (Baseline and Day 5) | Change in biomarker IL-10 as measured in blood samples. | Baseline and Day 5 | 
| Change in Interleukin 10 (IL-10) (Baseline and Pre-VAD) | Change in biomarker IL-10 as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Interleukin 10 (IL-10) (Baseline and Discharge) | Change in biomarker IL-10 as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Interleukin 10 (IL-10) (Baseline and Post-Discharge Follow-up) | Change in biomarker IL-10 as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 
| Change in Short-Chain Fatty Acids (Baseline and Day 5) | Change in short-chain fatty acids as measured in blood samples. | Baseline and Day 5 | 
| Change in Short-Chain Fatty Acids (Baseline and Pre-VAD) | Change in short-chain fatty acids as measured in blood samples. | Baseline and Pre-VAD (approximately Day 0-5) | 
| Change in Short-Chain Fatty Acids (Baseline and Discharge) | Change in short-chain fatty acids as measured in blood samples. | Baseline and Discharge (approximately Day 25) | 
| Change in Short-Chain Fatty Acids (Baseline and Post-Discharge Follow-up) | Change in short-chain fatty acids as measured in blood samples. | Baseline and Post-Discharge Follow-up (approximately Day 55) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-LVAD Infections | Number and type of infections experienced during index hospitalization following LVAD implantation | Day 25 | 
| Post-LVAD Length of Stay in intensive care unit | Number of days spent in intensive care unit following LVAD implantation. | Day 25 | 
| Post-LVAD Mortality | Number of participant deaths. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left Ventricular Assist Device (LVAD), Advanced Heart Failure, Mechanical Circulatory Support, Infection, Gut Microbiome