Interleukin-1 Blockade in Recently Decompensated Heart Failure (RED-HART)

Interleukin-1 Blockade in Recently Decompensated Heart Failure: A Randomized Placebo-controlled Double-blinded Study

The RED-HART is a randomized double-blinded placebo-controlled study of Anakinra (IL-1 blocker) in patients with recently decompensated heart failure to determine the safety and efficacy in terms of aerobic exercise capacity and ventilatory efficiency measured with a cardiopulmonary exercise test.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: Anakinra (weeks 1-2); Drug: Anakinra (weeks 3-12)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 all 2 conditions listed below:

   1. dyspnea or respiratory distress or tachypnea at rest or with minimal exertion;

   2. 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 X-Ray;
      • plasma Brain Natriuretic Peptide (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 <50%) at most recent assessment by any imaging modality (within 12 months).

3. The patient is now clinically stable and meets standard criteria for hospital discharge as documented by all the 3 conditions listed below:

   1. absence of dyspnea or pulmonary congestion/distress at rest;
   2. absence of pitting edema in the lower extremities, or in any other region;
   3. 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 of the treatment, and exercise protocol).
6. The patient has screening plasma C-reactive protein levels >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 cardiac resynchronization therapy (CRT), coronary artery revascularization procedures, or heart 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 (not including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]).
7. Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus).
8. Active infection (of any type);
9. Chronic/recurrent infectious disease (including Hepatitis B virus [HBV], Hepatitis C virus [HCV], and HIV/AIDS).
10. Prior (within the past 10 years) or current malignancy.
11. Any comorbidity limiting survival or ability to complete the study.
12. End stage kidney disease requiring renal replacement therapy.
13. Neutropenia (<2,000/mm3) or Thrombocytopenia (<50,000/mm3).
14. Pregnancy.
15. Angina, arrhythmias, or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing obtained during the baseline testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anakinra (short); Anakinra 100 mg daily for 2 weeks, followed by placebo for 10 weeks	Drug: Anakinra (weeks 1-2); Anakinra 100 mg daily for weeks 1 and 2
Experimental: Anakinra (long); Anakinra 100 mg daily for 12 weeks	Drug: Anakinra (weeks 1-2); Anakinra 100 mg daily for weeks 1 and 2; Drug: Anakinra (weeks 3-12); Other Names: Anakinra 100 mg daily for weeks 3 through 12
Placebo Comparator: Placebo; Placebo injections daily for 12 weeks	Drug: Placebo; Other Names: Placebo daily for week 1 through 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interval Changes in Peak Oxygen Consumption (VO2)	Interval changes in peak oxygen consumption (VO2) after 2 weeks of anakinra treatment.	Baseline to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Improvement	The Duke Activity Status Index questionnaire will be completed at enrollment and 12 weeks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores represent increased ability to perform daily activities and may be interpreted as improved quality of life.	12 weeks
Death or Hospital Admission for Heart Failure	We will monitor survival and hospitalization for heart failure throughout the 24 week follow-up	24 weeks

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Benjamin W Van Tassell, PharmD, Virginia Commonwealth University

Publications and helpful links

General Publications

• Van Tassell BW, Canada J, Carbone S, Trankle C, Buckley L, Oddi Erdle C, Abouzaki NA, Dixon D, Kadariya D, Christopher S, Schatz A, Regan J, Viscusi M, Del Buono M, Melchior R, Mankad P, Lu J, Sculthorpe R, Biondi-Zoccai G, Lesnefsky E, Arena R, Abbate A. Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial). Circ Heart Fail. 2017 Nov;10(11):e004373. doi: 10.1161/CIRCHEARTFAILURE.117.004373.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): September 23, 2016
• Study Completion (Actual): September 23, 2016

Study Registration Dates

• First Submitted: September 3, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimate): September 6, 2013

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: RED-HART (HM15339); 1R34HL117026 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No