Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2

• Status: Recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Treatments: Interleukin 1 Receptor Antagonist Protein

Criteria

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.