Heart Failure, Gastrointestinal Bleeding
Conditions
Keywords
Angiogenesis, Inflammation, Microbiome
Brief summary
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
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.
Interventions
Patients will receive 4 grams fish oil once daily
OTHERPlacebo
Standard of care
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has signed consent 2. Age \> 18 years 3. Subjects with a CF-LVAD or are scheduled to receive a CF-LVAD implant
Exclusion criteria
1. Psychiatric disorder or disease, irreversible cognitive dysfunction or psychosocial issues that might impair compliance with the study. 2. Patients already taking fish oil.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Markers of Angiogenesis - Angiopoietin 1/2 and VEGF | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | 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). |
| Change in Markers of Angiogenesis - TNF-alpha | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include TNF-alpha (pg/mL). |
| Change in Markers of Inflammation - C-Reactive Protein | Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | Markers of angiogenesis and inflammation will be measured on customized Luminex assay panels. These will include c-reactive protein (mg/dL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Gastrointestinal Bleeding | Rates of bleeding will be measured at 3 months, 6 months, and 12 months after randomization. | Rates of Gastrointestinal Bleeding will be assessed. |
| Changes in the Microbiome | The microbiome will be assessed at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization. | The microbiome will be assessed using rectal swabs. The swabs will be analyzed to determine the bacterial species present at each time point. |
Countries
United States
Participant flow
Pre-assignment details
Study terminated by PI for low/no enrollment prior to primary and secondary endpoints. All efforts were taken to gather all possible data.
Participants by arm
| Arm | Count |
|---|---|
| Primary Prevention Intervention 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.
Omega 3 fatty acids: Patients will receive 4 grams fish oil once daily | 12 |
| Primary Prevention Non-Intervention 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.
Placebo: Standard of care | 10 |
| Secondary Prevention Intervention 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.
Omega 3 fatty acids: Patients will receive 4 grams fish oil once daily | 1 |
| Secondary Prevention Non-Intervention 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.
Placebo: Standard of care | 0 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Study terminated by PI for low/no enrollment. All efforts were taken to gather all possible data. | 12 | 10 | 1 | 0 |
Baseline characteristics
| Characteristic | Primary Prevention Non-Intervention | Secondary Prevention Intervention | Total | Primary Prevention Intervention | Secondary Prevention Non-Intervention |
|---|---|---|---|---|---|
| Age, Continuous | 53.5 years | 76 years | 55 years | 55 years | — |
| Cerebrovascular accident and Stroke (CVA) Cerebrovascular accident and Stroke | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Cerebrovascular accident and Stroke (CVA) No Cerebrovascular accident and Stroke | 10 Participants | 1 Participants | 21 Participants | 10 Participants | 0 Participants |
| Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease | 0 Participants | 1 Participants | 5 Participants | 4 Participants | 0 Participants |
| Chronic Obstructive Pulmonary Disease (COPD) No Chronic Obstructive Pulmonary Disease | 10 Participants | 0 Participants | 18 Participants | 8 Participants | 0 Participants |
| Diabetes Mellitus (DM) Diabetes Mellitus | 2 Participants | 1 Participants | 10 Participants | 7 Participants | 0 Participants |
| Diabetes Mellitus (DM) No Diabetes Mellitus | 8 Participants | 0 Participants | 13 Participants | 5 Participants | 0 Participants |
| Dilated Cardiomyopathy Dilated | 8 Participants | 0 Participants | 15 Participants | 7 Participants | 0 Participants |
| Dilated Cardiomyopathy Not Dilated | 2 Participants | 1 Participants | 8 Participants | 5 Participants | 0 Participants |
| Hypertension (HTN) Hypertension | 5 Participants | 1 Participants | 13 Participants | 7 Participants | 0 Participants |
| Hypertension (HTN) No Hypertension | 5 Participants | 0 Participants | 10 Participants | 5 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 1 | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 2 | 5 Participants | 0 Participants | 11 Participants | 6 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 3 | 2 Participants | 0 Participants | 5 Participants | 3 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 6 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) Unknown | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ischemic Ischemic | 2 Participants | 1 Participants | 7 Participants | 4 Participants | 0 Participants |
| Ischemic Non-Ischemic | 8 Participants | 0 Participants | 16 Participants | 8 Participants | 0 Participants |
| LVAD Type HeartMate II | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| LVAD Type Heart Mate III | 5 Participants | 0 Participants | 14 Participants | 9 Participants | 0 Participants |
| LVAD Type Heartware Ventricular Assisted Device (HVAD) | 5 Participants | 0 Participants | 8 Participants | 3 Participants | 0 Participants |
| Obstructive Sleep Apnea (OSA) No Obstructive Sleep Apnea | 8 Participants | 1 Participants | 16 Participants | 7 Participants | 0 Participants |
| Obstructive Sleep Apnea (OSA) Obstructive Sleep Apnea | 2 Participants | 0 Participants | 7 Participants | 5 Participants | 0 Participants |
| Pre-LVAD Implant New York Heart Association Class (NYHA) 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pre-LVAD Implant New York Heart Association Class (NYHA) 2 | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Pre-LVAD Implant New York Heart Association Class (NYHA) 3 | 2 Participants | 0 Participants | 4 Participants | 2 Participants | 0 Participants |
| Pre-LVAD Implant New York Heart Association Class (NYHA) 4 | 7 Participants | 1 Participants | 17 Participants | 9 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 13 Participants | 8 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 0 Participants | 9 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 5 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 18 Participants | 9 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 12 | 0 / 10 | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 12 | 1 / 10 | 0 / 1 | 0 / 0 |
Outcome results
Primary
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).
Time frame: Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Population: Study terminated by PI for low/no enrollment prior to primary and secondary endpoints. All efforts were taken to gather all possible data.
Primary
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).
Time frame: Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Population: Study terminated by PI for low/no enrollment prior to primary and secondary endpoints. All efforts were taken to gather all possible data.
Primary
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).
Time frame: Markers will be measured at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Population: Study terminated by PI for low/no enrollment prior to primary and secondary endpoints. All efforts were taken to gather all possible data.
Secondary
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.
Time frame: The microbiome will be assessed at baseline at randomization, and at 3 months, 6 months, and 12 months after randomization.
Population: Study terminated by PI for low/no enrollment prior to primary and secondary endpoints. All efforts were taken to gather all possible data.
Secondary
Rates of Gastrointestinal Bleeding
Rates of Gastrointestinal Bleeding will be assessed.
Time frame: Rates of bleeding will be measured at 3 months, 6 months, and 12 months after randomization.
Population: Study terminated by PI for low/no enrollment. All efforts were taken to gather all possible data.