Interleukin-1 Blockade in Recently Decompensated Heart Failure

NCT ID: NCT01936909

Last Updated: 2017-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-09-23

Brief Summary

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Anakinra (short)

Anakinra 100 mg daily for 2 weeks, followed by placebo for 10 weeks

Group Type: EXPERIMENTAL

Anakinra (weeks 1-2)

Intervention Type: DRUG

Anakinra 100 mg daily for weeks 1 and 2

Anakinra (long)

Anakinra 100 mg daily for 12 weeks

Group Type: EXPERIMENTAL

Anakinra (weeks 1-2)

Intervention Type: DRUG

Anakinra 100 mg daily for weeks 1 and 2

Anakinra (weeks 3-12)

Intervention Type: DRUG

Placebo

Placebo injections daily for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Anakinra (weeks 1-2)

Anakinra 100 mg daily for weeks 1 and 2

Intervention Type: DRUG

Anakinra (weeks 3-12)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Anakinra 100 mg daily for weeks 3 through 12; Placebo daily for week 1 through 12

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 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

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Abbate, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Benjamin W Van Tassell, PharmD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29141858 (View on PubMed)

Other Identifiers

1R34HL117026

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RED-HART (HM15339)

Identifier Type: -

Identifier Source: org_study_id