Interleukin (IL)-1 Blockade in Acute Heart Failure (Anakinra ADHF)

Interleukin-1 Blockade in Acute Decompensated Heart Failure

Anakinra ADHF is a double-blind randomized clinical trial of anakinra, recombinant human interleukin-1 receptor blocker, or placebo in patients with acute decompensated heart failure with the aim to quench the acute inflammatory response, as measured by the area-under-the-curve for C reactive protein over 14 days.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Anakinra (high dose); Drug: Anakinra (standard dose); Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• 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 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All 5 criteria need to be met for enrollment of the patient in the study

1. Primary diagnosis of acute decompensated heart failure within the last 24 hours as evidenced by both of the following:

   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);

   i. pulmonary congestion/edema at physical exam OR chest x-ray; ii. plasma Brain Natriuretic Peptide (BNP) levels ≥200 pg/mL; iii.invasive measurement of left ventricular end-diastolic pressure >18 mmHg or of pulmonary artery occluding pressure (wedge) >16 mmHg.

2. Left ventricular systolic dysfunction (LVEF<40%) during index hospitalization or prior 12 months.
3. Age ≥18 years old
4. Willing and able to provide written informed consent.
5. Screening plasma C-reactive protein levels >5 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anakinra (short); Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14	Drug: Anakinra (high dose); Anakinra 100 mg daily twice daily for days 1, 2, and 3; Drug: Anakinra (standard dose); Anakinra 100 mg daily for days 4-14
Placebo Comparator: Placebo; Placebo injections twice daily for the first 3 days then once daily for days 4-14.	Drug: Placebo; Placebo twice daily for days 1, 2, and 3; Drug: Placebo; Placebo daily for days 4-14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C Reactive Protein	The proportional area-under-the-curve for plasma C reactive protein (CRP) levels measured during the first 3 days of admission. The proportion (y-axis) is calculated at each time-point with respect to the baseline CRP. The resultant y-axis is a unitless proportion. The x-axis is listed as "days"	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction	Change in left ventricular ejection fraction (LVEF) between admission and 14 day follow up. This value is expressed as absolute change in measured LVEF. For example, if baseline LVEF = 20% and 14 day LVEF = 25%, this would be reported as an absolute change of 5%.	14 days
Brachial Artery Vasoreactivity	Change in flow mediated vasodilatation (FMD) of the brachial artery. Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. The change is FMD is reported as the % change in FMD from baseline to 14 days.	14 days

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Benjamin W Van Tassell, PharmD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

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 (Estimate): May 5, 2016
• Last Update Submitted That Met QC Criteria: March 31, 2016
• Last Verified: March 1, 2016

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: VCU HM15347

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data may be available upon request