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Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2 (REDHART2)

Primary Purpose

Heart Failure, Systolic, Inflammation

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Placebo
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure, Systolic focused on measuring heart failure, inflammation, anakinra, exercise capacity

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All 6 criteria need to be met for enrollment of the patient in the study

  1. Primary diagnosis for hospitalization is decompensated heart failure established as the finding at admission of both conditions listed below:

    • dyspnea or respiratory distress or tachypnea at rest or with minimal exertion;
    • evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met):
    • pulmonary congestion/edema at physical exam OR chest XRay;
    • plasma BNP levels ≥200 pg/mL;
    • invasive measurement of left ventricular end-diastolic pressure >18 mmHg or of pulmonary artery occluding pressure (wedge) >16 mmHg.
  2. The patient has a prior documentation of impaired left ventricular systolic function (ejection fraction ≤40%) at most recent assessment by any imaging modality (within 12 months).
  3. The patient is now clinically stable, euvolemic, and meets standard criteria for hospital discharge as documented by all the 3 conditions listed below:

    • absence of dyspnea or pulmonary congestion/distress at rest;
    • absence of pitting edema in the lower extremities, or in any other region;
    • stable hemodynamic parameters (blood pressure, heart rate).
  4. The patient is of age ≥21 years old, and is willing and able to provide written informed consent.
  5. The patient is willing and able to comply with the protocol (i.e., self-administration, or exercise test).
  6. The patient has screening high sensitivity plasma C-reactive protein levels (hsCRP) >2 mg/L.

Exclusion Criteria:

Subjects will not be eligible if they meet any of the following 15 exclusion criteria.

  1. The primary diagnosis for admission is NOT decompensated heart failure, including diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias.
  2. Concomitant clinically significant comorbidities that would interfere with the execution or interpretation of the study 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.
  3. Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries.
  4. Previous or planned implantation of left ventricular assist devices or heart transplant.
  5. Chronic use of intravenous inotropes.
  6. 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).
  7. Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus).
  8. Active infection (of any type), including chronic/recurrent infectious disease (i.e. HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA.
  9. Active malignancy - excluding carcinoma in situ [any location] or localized non-melanoma skin cancer.
  10. Any comorbidity limiting survival or ability to complete the study.
  11. Stage V kidney disease or on renal-replacement therapy.
  12. Neutropenia (<1,500/mm3 or <1,000/mm3 in African-American patients).
  13. Pregnancy.
  14. Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations (i.e., peak respiratory exchange ratio VCO2/VO2 [RER]<1.0, reflecting sub-maximal test) that limit maximum exertion during CPX obtained during the baseline testing.
  15. Hypersensitivity to Kineret or to E. coli derived products. 16) Evidence of COVID19 within the last 60 days or recent (21 days) exposure to close personal contact.

Sites / Locations

  • Virginia Commonwealth UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

anakinra

placebo

Arm Description

Anakinra subcutaneous injection, 100 mg daily for 24 weeks

Placebo subcutaneous injection, daily for 24 weeks

Outcomes

Primary Outcome Measures

changes in peak oxygen consumption (VO2)
changes in peak oxygen consumption (VO2) after 24 weeks of treatment

Secondary Outcome Measures

changes in peak VO2 at earlier endpoints
changes in peak VO2 at earlier endpoints (6 and 12 weeks)
echocardiography assessments
evaluation of heart function by standard echocardiography assessments at 24 weeks
hemodynamic assessments
estimates of arterial elastance at 6, 12 and 24 weeks
Quality of Life Assessments
Duke Activity Status Index will be administered at 6, 12 and 24 weeks to provide patient perception of changes. Responses are yes or no, with yes responses corresponding to better clinical condition.
Biomarker - high sensitivity C-reactive protein (CRP)
The change in blood levels of CRP will be measured from baseline to 24 weeks.
Biomarker - N-terminal pro b-type Natriuretic Peptide (NT-proBNP)
The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.
Clinical Outcome - cardiac death
Instances of cardiac death during the study will be recorded
Clinical Outcome - hospitalization for heart failure
Instances of hospitalization for heart failure during the study will be recorded

Full Information

First Posted
January 2, 2019
Last Updated
May 1, 2023
Sponsor
Virginia Commonwealth University
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1. Study Identification

Unique Protocol Identification Number
NCT03797001
Brief Title
Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2
Acronym
REDHART2
Official Title
The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2019 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (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.
Yes

5. Study Description

Brief Summary
REDHART2 is a randomized, double-blinded, placebo-controlled trial to determine the effects of Anakinra on peak aerobic exercise capacity measured with a cardiopulmonary test after 24 weeks in patients with recently decompensated systolic heart failure and increased systemic inflammation.
Detailed Description
The REDHART2 (REcently Decompensated Heart failure Anakinra Response 2 Trial) study is a phase II clinical trial of anakinra or placebo to determine improvement in aerobic exercise capacity (by measuring maximal oxygen uptake (VO2)) in patients with recently decompensated systolic heart failure (HF). The recently completed pilot REDHART study showed anakinra treatment for 12 weeks led to a significant improvement in peak aerobic exercise capacity, whereas anakinra treatment for 2 weeks did not, and no significant changes were seen in placebo. The REDHART2 study is designed to expand and confirm the beneficial effect of sustained anakinra treatment (24 weeks) on peak VO2, and to explore the potential effect size on hospital readmissions for HF. The rationale of Interleukin-1 (IL-1) blockade with anakinra in heart failure stems from the evidence of a) reduced adverse cardiac remodeling and heart failure in animal models of acute myocardial infarction (AMI); b) reduced incidence of heart failure in patients with ST-segment elevation AMI; c) enhanced IL-1 activity in patients with heart failure, d) quenching of the acute inflammatory response in patients with acute decompensated heart failure, e) direct cardiodepressant effects of IL-1 in animal models, f) improved exercise capacity in pilot studies including patients with stable systolic heart failure, stable diastolic heart failure, and, recently decompensated systolic heart failure in the pilot REDHART study. Patients will be randomized 2:1 to active treatment, such that patients will be twice as likely to receive anakinra versus placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Systolic, Inflammation
Keywords
heart failure, inflammation, anakinra, exercise capacity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anakinra
Arm Type
Experimental
Arm Description
Anakinra subcutaneous injection, 100 mg daily for 24 weeks
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injection, daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Anakinra
Intervention Description
100 mg subcutaneous injection, daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
subcutaneous injection, daily for 24 weeks
Primary Outcome Measure Information:
Title
changes in peak oxygen consumption (VO2)
Description
changes in peak oxygen consumption (VO2) after 24 weeks of treatment
Time Frame
baseline - 24 weeks
Secondary Outcome Measure Information:
Title
changes in peak VO2 at earlier endpoints
Description
changes in peak VO2 at earlier endpoints (6 and 12 weeks)
Time Frame
baseline - 6 weeks and baseline - 12 weeks
Title
echocardiography assessments
Description
evaluation of heart function by standard echocardiography assessments at 24 weeks
Time Frame
baseline - 24 weeks
Title
hemodynamic assessments
Description
estimates of arterial elastance at 6, 12 and 24 weeks
Time Frame
baseline - 24 weeks
Title
Quality of Life Assessments
Description
Duke Activity Status Index will be administered at 6, 12 and 24 weeks to provide patient perception of changes. Responses are yes or no, with yes responses corresponding to better clinical condition.
Time Frame
baseline - 24 weeks
Title
Biomarker - high sensitivity C-reactive protein (CRP)
Description
The change in blood levels of CRP will be measured from baseline to 24 weeks.
Time Frame
baseline - 24 weeks
Title
Biomarker - N-terminal pro b-type Natriuretic Peptide (NT-proBNP)
Description
The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.
Time Frame
baseline - 24 weeks
Title
Clinical Outcome - cardiac death
Description
Instances of cardiac death during the study will be recorded
Time Frame
baseline - 24 weeks
Title
Clinical Outcome - hospitalization for heart failure
Description
Instances of hospitalization for heart failure during the study will be recorded
Time Frame
baseline - 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All 6 criteria need to be met for enrollment of the patient in the study Primary diagnosis for hospitalization is decompensated heart failure established as the finding at admission of both conditions listed below: dyspnea or respiratory distress or tachypnea at rest or with minimal exertion; evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met): pulmonary congestion/edema at physical exam OR chest XRay; plasma BNP levels ≥200 pg/mL; invasive measurement of left ventricular end-diastolic pressure >18 mmHg or of pulmonary artery occluding pressure (wedge) >16 mmHg. The patient has a prior documentation of impaired left ventricular systolic function (ejection fraction ≤40%) at most recent assessment by any imaging modality (within 12 months). The patient is now clinically stable, euvolemic, and meets standard criteria for hospital discharge as documented by all the 3 conditions listed below: absence of dyspnea or pulmonary congestion/distress at rest; absence of pitting edema in the lower extremities, or in any other region; stable hemodynamic parameters (blood pressure, heart rate). The patient is of age ≥21 years old, and is willing and able to provide written informed consent. The patient is willing and able to comply with the protocol (i.e., self-administration, or exercise test). The patient has screening high sensitivity plasma C-reactive protein levels (hsCRP) >2 mg/L. Exclusion Criteria: Subjects will not be eligible if they meet any of the following 15 exclusion criteria. The primary diagnosis for admission is NOT decompensated heart failure, including diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias. Concomitant clinically significant comorbidities that would interfere with the execution or interpretation of the study 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. Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries. Previous or planned implantation of left ventricular assist devices or heart transplant. Chronic use of intravenous inotropes. 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 (i.e. HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA. Active malignancy - excluding carcinoma in situ [any location] or localized non-melanoma skin cancer. Any comorbidity limiting survival or ability to complete the study. Stage V kidney disease or on renal-replacement therapy. Neutropenia (<1,500/mm3 or <1,000/mm3 in African-American patients). Pregnancy. Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations (i.e., peak respiratory exchange ratio VCO2/VO2 [RER]<1.0, reflecting sub-maximal test) that limit maximum exertion during CPX obtained during the baseline testing. Hypersensitivity to Kineret or to E. coli derived products. 16) Evidence of COVID19 within the last 60 days or recent (21 days) exposure to close personal contact.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benjamin Van Tassell, PharmD
Phone
804-828-4583
Email
bvantassell@vcu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Van Tassell, PharmD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Van Tassell, PharmD
Phone
804-828-4583
Email
bvantassell@vcu.edu

12. IPD Sharing Statement

Citations:
PubMed Identifier
35706006
Citation
Van Tassell B, Mihalick V, Thomas G, Marawan A, Talasaz AH, Lu J, Kang L, Ladd A, Damonte JI, Dixon DL, Markley R, Turlington J, Federmann E, Del Buono MG, Biondi-Zoccai G, Canada JM, Arena R, Abbate A. Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. J Transl Med. 2022 Jun 15;20(1):270. doi: 10.1186/s12967-022-03466-9.
Results Reference
derived
PubMed Identifier
35283262
Citation
Sedhai YR, Patel NK, Mihalick V, Talasaz A, Thomas G, Denlinger BL, Damonte JI, Del Buono MG, Federmann E, Hardin M, Ibe I, Harmon M, Van Tassell B, Abbate A. Heart failure clinical trial enrollment at a rural satellite hospital. Contemp Clin Trials. 2022 Apr;115:106731. doi: 10.1016/j.cct.2022.106731. Epub 2022 Mar 11.
Results Reference
derived

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Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2

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