Interleukin-1 Blockade in HF With Preserved EF

NCT02173548 | Completed Phase 2 Results DMC

• 2 other identifiers: HM200001181R34HL118348-01A1
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

• Heart Failure with Preserved Ejection Fraction (HFpEF) is a common form of heart failure
• Standard treatment for heart failure, show less than ideal results in HFpEF
• Evidence of systemic inflammation is common in all forms of heart failure, including HFpEF
• The main hypothesis of this study is that systemic inflammation contributes to heart failure symptoms and exercise limitations in patients with HFpEF
• The main objective is to treat patients with HFpEF and evidence of systemic inflammation with an anti-inflammatory drug targeting Interleukin-1 (or placebo) to determine effects on cardiovascular function

Conditions

Heart Failure With Normal Ejection Fraction

Keywords

heart failure; HFpEF; diastole; diastolic heart failure; inflammation; interleukin-1; C-reactive protein

Outcome Measures

Primary Outcomes (2)

• Change in Aerobic Exercise Capacity

  Absolute changes in aerobic exercise capacity (peak VO2) after 12 weeks treatment. This will compare patients treated with anakinra and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.

  Baseline to 12 weeks

• Change in Ventilatory Eefficiency

  Absolute changes in ventilatory efficiency (VE/VCO2 \[carbon dioxide\] slope) after 12 weeks treatment. This will compare patients treated with anakinra vs placebo, and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.

  Baseline to 12 weeks

Secondary Outcomes (6)

• Echocardiographic Assessment of Diastolic and Systolic Function (Left Ventricular Ejection Fraction)

  12 weeks

• Change in Diastolic and Contractile Reserve (e' Velocity and E/e' Ratio)

  Baseline to 12 weeks

• Change in Inflammation (C Reactive Protein Levels)

  Baseline to 12 weeks

• Change in Quality of Life Questionnaire-Minnesota Living With Heart Failure Questionnaire (MLWHF)

  Baseline to 24 weeks

• Change in Quality of Life Questionnaire-Duke Activity Status Index (DASI)

  Baseline to 12 weeks

Study Arms (2)

Anakinra

ACTIVE COMPARATOR

Anakinra 100 mg given subcutaneously once daily for 12 weeks

Drug: Anakinra

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

Anakinra DRUG

Also known as: Kineret

Anakinra

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptoms and signs of heart failure (NYHA II-III) and prior hospitalization for heart failure
• Recent Imaging Study (\<12 months) showing LVEF\>50% and Left Ventricular End Diastolic Volume Index (LVEDVI) \<97ml/m2
• Evidence of abnormal LV relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following
• a. Invasive Hemodynamic measurements i. mean Pulmonary Capillary Wedge Pressure (mPCW) \>12 ii. Left Ventricular End Diastolic Pressure (LVEDP) \>16 mmHg b. Tissue Doppler Echocardiogram i. E/E' \>15 ii. E/E' 8-15 and one of the following: Left Ventricular Hypertrophy (LVH), Atrial fibrillation, Left Atrial Enlargement (LAE), E/A \<0.5 + DT (Deceleration Time) \>280, c. Biomarkers i. Brain Natriuretic Peptide (BNP) \>200pg/ml (not due to a concomitant disease such as pulmonary arterial hypertension, pulmonary embolism, acute renal failure, or other)
• CRP \> 2.0 mg/L

You may not qualify if:

• Age \<21
• Concomitant conditions or treatments which would affect completion of the study or interpretation of the study tests including but not limited to the following conditions:
• physical inability to walk or run on a treadmill
• angina or evidence of spontaneous or inducible ischemia
• uncontrolled arterial hypertension
• atrial fibrillation (or other arrhythmias)
• moderate to severe valvular heart disease
• chronic pulmonary disease
• anemia (Hgb\<10 g/dl)
• Angina, uncontrolled hypertension or electrocardiograph (ECG) changes (i.e. ischemia, arrhythmias) that limit maximum exertion during cardiopulmonary exercise testing
• Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable cardioverter defibrillator (AICD) or coronary revascularization or cardiac surgery
• Active infection including chronic infection
• Active cancer (or prior diagnosis of cancer within the past 10 years)
• Recent (\<14 days) or active use of immunosuppressive drugs (including but not limited to high-dose corticosteroids \[\>1\_mg/kg of prednisone equivalent\], Tumor Necrosis Factor (TNF)-α blockers, cyclosporine) not including Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or corticosteroids used for IV dye allergy only)
• Chronic auto-immune or auto-inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus)

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• Van Tassell BW, Trankle CR, Canada JM, Carbone S, Buckley L, Kadariya D, Del Buono MG, Billingsley H, Wohlford G, Viscusi M, Oddi-Erdle C, Abouzaki NA, Dixon D, Biondi-Zoccai G, Arena R, Abbate A. IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2018 Aug;11(8):e005036. doi: 10.1161/CIRCHEARTFAILURE.118.005036.

  PMID: 30354558 DERIVED

• Van Tassell BW, Buckley LF, Carbone S, Trankle CR, Canada JM, Dixon DL, Abouzaki N, Oddi-Erdle C, Biondi-Zoccai G, Arena R, Abbate A. Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2). Clin Cardiol. 2017 Sep;40(9):626-632. doi: 10.1002/clc.22719. Epub 2017 May 5.

  PMID: 28475816 DERIVED

MeSH Terms

Conditions

Heart Failure; Heart Murmurs; Heart Failure, Diastolic; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Antonio Abbate, MD, PhD
• Organization: Virginia Commonwealth University

antonio.abbate@vcuhealth.org

(804) 828-0513

Study Officials

• Antonio Abbate, MD, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• Benjamin Van Tassell, PharmD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 25, 2014
• Study Start: September 1, 2014
• Primary Completion: April 11, 2017
• Study Completion: June 1, 2017
• Last Updated: June 19, 2018
• Results First Posted: June 19, 2018

Record last verified: 2018-05

Locations

US (1)