Back to resultsThe Effects of IL-1 Blockade on Inotrope Sensitivity in Patients With Heart Failure (AID-HEART) (AID-HEART)
Primary Purpose
Heart Failure
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Inotrope sensitivity, IL-1 Blockade, Subcutaneous (SC), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV, 6 Minute Walk Test (6MWT)
Eligibility Criteria
Inclusion Criteria: Primary diagnosis for the clinic visit is stage D heart failure being on chronic stable dose of inotrope therapy (dobutamine or milrinone for the previous 28 days) Prior documentation of impaired left ventricular systolic function (ejection fraction <50%) at most recent assessment by any imaging modality (within 12 months) Stable dose of inotrope treatment without a recent hospitalization within the previous month Age ≥21 years and willing/able to provide written informed consent The patient is willing and able to comply with the protocol (i.e. self administration of the treatment, and exercise protocol). Screening plasma C-reactive protein levels >2 mg/L Exclusion Criteria: Concomitant clinically significant comorbidities including (but not limited to) acute coronary syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders affecting respiration that would interfere with the execution, interpretation, or completion of the study Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries Previous or planned implantation of left ventricular assist devices or heart transplant within the next 3 months Recent (<14 days) use of immunosuppressive or anti-inflammatory drugs (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs) Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus) Active infection (of any type), including chronic/recurrent infectious disease (including HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA Prior (within the past 5 years) or current malignancy on targeted treatment - excluding carcinoma in situ [any location] or localized non-melanoma skin cancer Stage V kidney disease or on renal-replacement therapy Neutropenia (<1,500/mm3 or <1,000/mm3 in African-American patients) Pregnancy or breastfeeding Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations that limit 6MWD obtained during the baseline testing Hypersensitivity to anakinra or to E. coli derived products
Sites / Locations
- Virginia Commonwealth UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment arm
Arm Description
Outcomes
Primary Outcome Measures
Percent reduction in high-sensitive C-Reactive Protein (hsCRP, a biomarker for IL-1 activity)
Percent reduction in hsCRP (a biomarker for IL-1 activity) at 1 month and 3 months of anakinra treatment.
Secondary Outcome Measures
Change of inotrope dose (over 24 hrs) as a percentage of baseline inotrope dose (over 24 hrs)
Inotrope use increases the risk of morbidity and mortality in patients with stage D HF. We hypothesize that anti-inflammatory treatment with IL-1 blockade (anakinra) will improve sensitivity to inotropes and therefore reduce the dose of inotropes required to alleviate HF symptoms in patients with end stage HF.
Change in exercise capacity will be measured with a 6-minute walk test (6MWT)
The 6-minute walk test (6MWT) is strongly correlated with cardiac output and disease severity and is an independent predictor of HF hospitalizations and mortality.
Full Information
NCT ID
NCT06062966
First Posted
September 25, 2023
Last Updated
October 24, 2023
Sponsor
Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT06062966
Brief Title
The Effects of IL-1 Blockade on Inotrope Sensitivity in Patients With Heart Failure (AID-HEART)
Acronym
AID-HEART
Official Title
The Effects of IL-1 Blockade on Inotrope Sensitivity in Patients With Heart Failure (AID-HEART)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
End-stage heart failure (HF) is a progressive illness with a mortality rate similar to most advanced cancers.Roughly 5% of patients with HF have end-stage disease that is refractory to medical therapy (stage D heart failure). When patients reach this point in their disease, the only treatments known to prolong life are cardiac transplantation or left ventricular assist devices. In patients who do not qualify for these options, or elect a palliative approach, inotropes are frequently used to improve hemodynamics through an increase in cardiac output and reduction in filling pressures. While inotropes provide profound symptomatic relief, these benefits are accompanied by significant risks of progressive adverse cardiac remodeling, arrhythmias, and sudden death. There is, therefore, an urgent need to develop strategies to reduce the dose or duration of inotrope use in the management of patients with stage D of HF.
Detailed Description
Heart failure (HF) represents a leading cause of morbidity and mortality worldwide. Despite improvements in treatments and widespread efforts to implement guideline directed medical therapies, a growing population of patients with end-stage HF has limited treatment options to improve their quality and quantity of life. When patients reach this point in their disease, the only treatments known to prolong life are cardiac transplantation or left ventricular assist devices. In patients who do not qualify for these options, intravenous (IV) drugs that directly stimulate increased cardiac output ("inotropes") are frequently used to offer symptomatic relief. Inotropes exert their pharmacologic effects through direct activation of the beta-adrenergic receptors in the heart that increase heart rate and contractility. Unfortunately, however, the relief of symptoms from inotropes is accompanied by dose-dependent increased risks of progressive adverse cardiac remodeling, arrhythmias, and sudden death. There is therefore an urgent need to develop treatments that minimize the dosing requirements for inotropes or improve responsiveness to these agents.
Inflammation has been recognized as a major pathophysiological contributor to HF. Interleukin (IL)-1 is a potent apical inflammatory cytokine that is abundant in HF patients and correlates with disease severity. Preclinical data have shown that IL-1 is sufficient to induce cardiac dysfunction, desensitize beta-adrenergic receptors (impaired responsiveness to inotropes), and reduce exercise capacity. Among the observed effects of IL-1 in these models of HF, the impaired responsiveness to inotropes showed the greatest signal-to-noise ratio, suggesting a large potential effect size for IL-1 blockade to translated to human subjects. In a 12-week pilot clinical trial in stable HF patients not receiving IV inotropes, daily administration of an IL-1 antagonist (anakinra) improved exercise capacity. However, IL-1 blockade has not yet been evaluated in patients with more advanced HF requiring inotrope therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Inotrope sensitivity, IL-1 Blockade, Subcutaneous (SC), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV, 6 Minute Walk Test (6MWT)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is a pilot study designed to treat 20 subjects to provide the preliminary data necessary to inform the design of subsequent hypothesis-driven studies.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Anakinra
Intervention Description
Anakinra 100 mg SC daily will be administered to sujects on chronic inotrope treatment who are not candidates for transplantation or left ventricular assist device (LVAD).
Primary Outcome Measure Information:
Title
Percent reduction in high-sensitive C-Reactive Protein (hsCRP, a biomarker for IL-1 activity)
Description
Percent reduction in hsCRP (a biomarker for IL-1 activity) at 1 month and 3 months of anakinra treatment.
Time Frame
Months 1 and 3 of treatment
Secondary Outcome Measure Information:
Title
Change of inotrope dose (over 24 hrs) as a percentage of baseline inotrope dose (over 24 hrs)
Description
Inotrope use increases the risk of morbidity and mortality in patients with stage D HF. We hypothesize that anti-inflammatory treatment with IL-1 blockade (anakinra) will improve sensitivity to inotropes and therefore reduce the dose of inotropes required to alleviate HF symptoms in patients with end stage HF.
Time Frame
Months 1 and 3 of treatment
Title
Change in exercise capacity will be measured with a 6-minute walk test (6MWT)
Description
The 6-minute walk test (6MWT) is strongly correlated with cardiac output and disease severity and is an independent predictor of HF hospitalizations and mortality.
Time Frame
Baseline, Months 1 and 3 of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Primary diagnosis for the clinic visit is stage D heart failure being on chronic stable dose of inotrope therapy (dobutamine or milrinone for the previous 28 days)
Prior documentation of impaired left ventricular systolic function (ejection fraction <50%) at most recent assessment by any imaging modality (within 12 months)
Stable dose of inotrope treatment without a recent hospitalization within the previous month
Age ≥21 years and willing/able to provide written informed consent
The patient is willing and able to comply with the protocol (i.e. self administration of the treatment, and exercise protocol).
Screening plasma C-reactive protein levels >2 mg/L
Exclusion Criteria:
Concomitant clinically significant comorbidities including (but not limited to) acute coronary syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders affecting respiration that would interfere with the execution, interpretation, or completion of the study
Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries
Previous or planned implantation of left ventricular assist devices or heart transplant within the next 3 months
Recent (<14 days) use of immunosuppressive or anti-inflammatory drugs (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs)
Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus)
Active infection (of any type), including chronic/recurrent infectious disease (including HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA
Prior (within the past 5 years) or current malignancy on targeted treatment - excluding carcinoma in situ [any location] or localized non-melanoma skin cancer
Stage V kidney disease or on renal-replacement therapy
Neutropenia (<1,500/mm3 or <1,000/mm3 in African-American patients)
Pregnancy or breastfeeding
Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations that limit 6MWD obtained during the baseline testing
Hypersensitivity to anakinra or to E. coli derived products
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benjamin VanTassell
Phone
8048284583
Email
bvantassell@vcu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Azita Talasaz
Organizational Affiliation
Virginia Coomonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23284
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Azita Talasazah
Phone
804-828-4583
Email
talasazah@vcu.edu
First Name & Middle Initial & Last Name & Degree
Benjamin Van Tassell
Phone
8048284583
Email
bvantassell@vcu.edu
12. IPD Sharing Statement
Learn more about this trial
The Effects of IL-1 Blockade on Inotrope Sensitivity in Patients With Heart Failure (AID-HEART)
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