Heart Failure
Conditions
Keywords
Ventricular Assist Device, Recovery of Function
Brief summary
Heart failure remains a major cause of morbidity and mortality. Many patients with heart failure receive support from a left ventricular assist device (LVAD) at some point in the course of their disease. Some of these LVAD patients experience a durable recovery after ventricular unloading with an LVAD, which may be associated with inhibition of inflammatory cytokines. This small pilot study aims to determine the biologic and clinical efficacy of an interleukin-1 receptor antagonist (Anakinra) at inducing myocardial recovery in patients supported with left ventricular assist devices.
Detailed description
More than 5 million Americans have heart failure, a number that is expected to increase 25% by the year 2030. Fifty percent of individuals diagnosed with heart failure die within 5 years of diagnosis. Of those patients who currently have heart failure, 5-10% have Stage D disease, requiring specialized interventions such as chronic inotropic support, mechanical circulatory support, or transplantation. Transplantation is considered curative for heart failure, but only about 2,200 heart transplants take place each year. Due to the imbalance between donors and possible recipients, a large number of patients remain who could benefit from transplantation that will never receive a heart. Many patients receive left ventricular assist devices (LVADs) to support their failing hearts, increasing their chances of survival while they wait to undergo transplantation. It has been shown that up to 19% of patients show durable echocardiographic recovery (as measured by left ventricular ejection fraction \>40%) after ventricular unloading with an LVAD. Recovery mediated by unloading with the LVAD causes several changes at the molecular level. However, the mechanisms underlying recovery at the cellular level, also known as reverse remodeling, are only recently being studied. Thus, the window of opportunity to develop adjuvant treatments to enhance recovery is just now opening. Interestingly, patients that experience durable echocardiographic recovery have higher circulating levels of anti-inflammatory cytokines. Inhibition of inflammatory cytokines, such as with the use of receptor antagonists for inflammation-associated cytokines like Anakinra, has also been shown to reduce adverse myocardial remodeling after ischemic events and to increase exercise activity in patients with systolic heart failure. This study proposes the exogenous administration of Anakinra to end-stage heart failure patients supported with LVADs in an effort to increase both the number of patients who experience recovery and the magnitude of recovery. While this is a small trial aimed primarily at demonstrating biologic efficacy of Anakinra, clinical efficacy in this study is also investigated. Encouraging results in this pilot study may prompt the creation of a randomized, controlled trial designed to demonstrate efficacy from a functional clinical standpoint.
Interventions
DRUGAnakinra
Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* To qualify for inclusion, patients must meet the following criteria: age \>18 years at date of LVAD implantation who require circulatory support with an LVAD for either a bridge-to-transplant or destination therapy indication. * They must also be judged by the implanting surgeon to have an expected survival to trial completion (approximately 6 months after implantation), without regard to the likelihood of cardiac transplantation.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biologic Efficacy: Inflammation Marker - C-Reactive Protein | 6 months post treatment | The primary endpoint was a reduction in inflammatory markers, specifically C-reactive protein (CRP). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biologic Efficacy: Inflammation Marker - Neutrophil Count | 6 months post treatment | Secondary endpoints included the measure of additional inflammatory markers, including neutrophil count. |
| Clinical Efficacy: Ejection Fraction | 6 months post treatment | Clinical efficacy was a secondary endpoint that was measured using ejection fraction (EF) |
| Biologic Efficacy: Inflammation Marker - TNFalpha | 6 months post treatment | Secondary endpoints included the measure of additional inflammatory markers, including TNFalpha. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anakinra Arm All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.
Anakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Anakinra Arm |
|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Biologic Efficacy: Inflammation Marker - C-Reactive Protein
The primary endpoint was a reduction in inflammatory markers, specifically C-reactive protein (CRP).
Time frame: 6 months post treatment
Population: Patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - C-Reactive Protein | Prior to Anakinra | 2.5 mg/dL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - C-Reactive Protein | After Anakinra | 0.6 mg/dL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - C-Reactive Protein | At 6 months | 0.6 mg/dL |
Secondary
Biologic Efficacy: Inflammation Marker - Neutrophil Count
Secondary endpoints included the measure of additional inflammatory markers, including neutrophil count.
Time frame: 6 months post treatment
Population: Patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - Neutrophil Count | Prior to Anakinra | 6.4 10^3 cells/µL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - Neutrophil Count | After Anakinra | 5.0 10^3 cells/µL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - Neutrophil Count | At 6 months | 4.4 10^3 cells/µL |
Secondary
Biologic Efficacy: Inflammation Marker - TNFalpha
Secondary endpoints included the measure of additional inflammatory markers, including TNFalpha.
Time frame: 6 months post treatment
Population: Patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - TNFalpha | Prior to Anakinra | 4 pg/mL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - TNFalpha | After Anakinra | 9 pg/mL |
| Anakinra Arm | Biologic Efficacy: Inflammation Marker - TNFalpha | At 6 months | 4 pg/mL |
Secondary
Clinical Efficacy: Ejection Fraction
Clinical efficacy was a secondary endpoint that was measured using ejection fraction (EF)
Time frame: 6 months post treatment
Population: Patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra Arm | Clinical Efficacy: Ejection Fraction | Prior to Anakinra | 15 percentage of blood leaving heart |
| Anakinra Arm | Clinical Efficacy: Ejection Fraction | After Anakinra | 15 percentage of blood leaving heart |
| Anakinra Arm | Clinical Efficacy: Ejection Fraction | At 6 months | 25 percentage of blood leaving heart |