Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2

Last updated: November 4, 2024
Sponsor: Virginia Commonwealth University
Overall Status: Completed

Phase

2

Condition

Inflammation

Heart Failure

Chest Pain

Treatment

Anakinra

Placebo

Clinical Study ID

NCT03797001
REDHART2 HM20014686
  • Ages > 21
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 asthe 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 leastone 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 ofpulmonary artery occluding pressure (wedge) >16 mmHg.

  1. 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).

  2. The patient is now clinically stable, euvolemic, and meets standard criteria forhospital 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).

  1. The patient is of age ≥21 years old, and is willing and able to provide writteninformed consent.

  2. The patient is willing and able to comply with the protocol (i.e.,self-administration, or exercise test).

  3. The patient has screening high sensitivity plasma C-reactive protein levels (hsCRP) >2 mg/L.

Exclusion

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, includingdiagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- orbrady-arrhythmias.

  2. Concomitant clinically significant comorbidities that would interfere with theexecution or interpretation of the study including but not limited to acute coronarysyndromes, uncontrolled hypertension or orthostatic hypotension, tachy- orbrady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disordersaffecting respiration.

  3. Recent (previous 3 months) or planned resynchronization therapy (CRT), or valvesurgeries.

  4. Previous or planned implantation of left ventricular assist devices or hearttransplant.

  5. Chronic use of intravenous inotropes.

  6. Recent (<14 days) use of immunosuppressive or anti-inflammatory drugs (includingoral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but notincluding inhaled or low dose oral corticosteroids or non-steroidalanti-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 localizednon-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 othernon-cardiac limitations (i.e., peak respiratory exchange ratio VCO2/VO2 [RER]<1.0,reflecting sub-maximal test) that limit maximum exertion during CPX obtained duringthe baseline testing.

  15. Hypersensitivity to Kineret or to E. coli derived products. 16) Evidence of COVID19within the last 60 days or recent (21 days) exposure to close personal contact.

Study Design

Total Participants: 102
Treatment Group(s): 2
Primary Treatment: Anakinra
Phase: 2
Study Start date:
January 04, 2019
Estimated Completion Date:
July 22, 2024

Study 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.

Connect with a study center

  • Virginia Commonwealth University

    Richmond, Virginia 23298
    United States

    Site Not Available

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