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

• ClinicalTrials.gov Identifier: NCT03797001
• Recruitment Status: Recruiting
• First Posted: January 8, 2019
• Last Update Posted: January 5, 2024
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

Tracking Information

• First Submitted Date: January 2, 2019
• First Posted Date: January 8, 2019
• Last Update Posted Date: January 5, 2024
• Actual Study Start Date: January 4, 2019
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 4, 2019)

changes in peak oxygen consumption (VO2) [ Time Frame: baseline - 24 weeks ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 1, 2019)

• changes in peak VO2 at earlier endpoints [ Time Frame: baseline - 6 weeks and baseline - 12 weeks ]
  changes in peak VO2 at earlier endpoints (6 and 12 weeks)
• echocardiography assessments [ Time Frame: baseline - 24 weeks ]
  evaluation of heart function by standard echocardiography assessments at 24 weeks
• hemodynamic assessments [ Time Frame: baseline - 24 weeks ]
  estimates of arterial elastance at 6, 12 and 24 weeks
• Quality of Life Assessments [ Time Frame: baseline - 24 weeks ]
  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) [ Time Frame: baseline - 24 weeks ]
  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) [ Time Frame: baseline - 24 weeks ]
  The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.
• Clinical Outcome - cardiac death [ Time Frame: baseline - 24 weeks ]
  Instances of cardiac death during the study will be recorded
• Clinical Outcome - hospitalization for heart failure [ Time Frame: baseline - 24 weeks ]
  Instances of hospitalization for heart failure during the study will be recorded

Original Secondary Outcome Measures (submitted: January 4, 2019)

• changes in peak VO2 at earlier endpoints [ Time Frame: baseline - 6 weeks and baseline - 12 weeks ]
  changes in peak VO2 at earlier endpoints (6 and 12 weeks)
• echocardiography assessments [ Time Frame: baseline - 24 weeks ]
  evaluation of heart function by standard echocardiography assessments at 24 weeks
• hemodynamic assessments [ Time Frame: baseline - 24 weeks ]
  estimates of arterial elastance at 6, 12 and 24 weeks
• Quality of Life Assessments [ Time Frame: baseline - 24 weeks ]
  Cardiomyopathy Questionnaire will be administered at 6, 12 and 24 weeks to provide patient perception of changes
• Biomarker - high sensitivity C-reactive protein (CRP) [ Time Frame: baseline - 24 weeks ]
  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) [ Time Frame: baseline - 24 weeks ]
  The change in blood levels of NT-proBNP will be measured from baseline to 24 weeks.
• Clinical Outcome - cardiac death [ Time Frame: baseline - 24 weeks ]
  Instances of cardiac death during the study will be recorded
• Clinical Outcome - hospitalization for heart failure [ Time Frame: baseline - 24 weeks ]
  Instances of hospitalization for heart failure during the study will be recorded

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2
• Official Title: The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Heart Failure, Systolic
• Inflammation

Intervention

• Drug: Anakinra
  100 mg subcutaneous injection, daily for 24 weeks
• Drug: Placebo
  subcutaneous injection, daily for 24 weeks

Study Arms

• Experimental: anakinra
  Anakinra subcutaneous injection, 100 mg daily for 24 weeks
  Intervention: Drug: Anakinra
• Placebo Comparator: placebo
  Placebo subcutaneous injection, daily for 24 weeks
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 4, 2019): 102
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Benjamin Van Tassell, PharmD; 804-828-4583; bvantassell@vcu.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03797001
• Other Study ID Numbers: REDHART2 HM20014686
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Virginia Commonwealth University
• Original Responsible Party: Same as current
• Current Study Sponsor: Virginia Commonwealth University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Benjamin Van Tassell, PharmD; Virginia Commonwealth University

• PRS Account: Virginia Commonwealth University
• Verification Date: January 2024