Efficacy of Omega-3 Fatty Acid Therapy in Preventing Gastrointestinal Bleeding in Patients With CF-LVAD

Study Overview
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Brief Summary
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This study evaluates the efficacy of high-dose fish oil in decreasing rates of gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices. Half of the patients without history of bleeding will receive fish oil while the other half will not. Half of the patients with history of bleeding will receive fish oil while the other half will not. Markers of angiogenesis and inflammation, as well as changes in the microbiome will be assessed in each group.

Detailed Description
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A potential mechanism of bleeding in patients with continuous-flow left ventricular assist devices (CF-LVAD) is dysfunctional angiogenesis. Angiogenesis is a complicated process controlled by several markers. Previous studies have shown that elevated Angiopoietin-2 and TNF-alpha are associated with bleeding events in CF-LVAD patients. Fish oil has anti-inflammatory and potentially anti-angiogenic properties. A retrospective study of CF-LVAD patients on high-dose fish oil showed a marked decrease in gastrointestinal bleeding rates in these patients. Additionally, these patients had lower levels of circulating Angiopoietin-2. Fish oil is known to have an effect on the microbiome, and the aforementioned effects may be seen in changes of the microbiota.

Official Title
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Open-Label Prospective Randomized Control Trial to Investigate the Efficacy of Omega-3 Fatty Acid Therapy in Preventing Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Device

Conditions
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Heart Failure, Gastrointestinal Bleeding

Intervention / Treatment
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* Drug: Omega 3 fatty acids
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed consent Age > 18 years Subjects with a CF-LVAD or are scheduled to receive a CF-LVAD implant Exclusion Criteria: Psychiatric disorder or disease, irreversible cognitive dysfunction or psychosocial issues that might impair compliance with the study. Patients already taking fish oil.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary Prevention Intervention<br>In patients with CF-LVAD who have not had a gastrointestinal bleed, patients randomized to intervention will receive 4 grams of Nature Made Ultra Omega-3 Fish Oil once daily for 1 year along with standard of care. | Drug: Omega 3 fatty acids<br>* Patients will receive 4 grams fish oil once daily<br>|
| Placebo Comparator: Primary Prevention Non-Intervention<br>In patients with CF-LVAD who have not had a gastrointestinal bleed, patients randomized to placebo will receive no fish oil and only standard of care. | Other: Placebo<br>* Standard of care<br>|
| Experimental: Secondary Prevention Intervention<br>In patients with CF-LVAD who have had a gastrointestinal bleed, patients randomized to intervention will receive 4 grams of Nature Made Ultra Omega-3 Fish Oil once daily for 1 year along with standard of care. | Drug: Omega 3 fatty acids<br>* Patients will receive 4 grams fish oil once daily<br>|
| Placebo Comparator: Secondary Prevention Non-Intervention<br>In patients with CF-LVAD who have had a gastrointestinal bleed, patients randomized to placebo will receive no fish oil and only standard of care. | Other: Placebo<br>* Standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Markers of Angiogenesis - Angiopoietin 1/2 and VEGF | Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include Angiopoietin-1 (ng/mL), Angiopoietin-2 (ng/mL), and VEGF (ng/mL). | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | 
| Change in Markers of Angiogenesis - TNF-alpha | Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include TNF-alpha (pg/mL). | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | 
| Change in Markers of Inflammation - C-Reactive Protein | Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include c-reactive protein (mg/dL). | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Gastrointestinal Bleeding | Rates of Gastrointestinal Bleeding will be assessed. | Rates of bleeding will be measured at 3 months, 6 months, and 12 months after randomization. | 
| Changes in the Microbiome | The microbiome will be assessed using rectal swabs. The swabs will be analyzed to determine the bacterial species present at each time point. | The microbiome will be assessed at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiogenesis, Inflammation, Microbiome