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

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: Anakinra (high dose); Drug: Placebo; Drug: Anakinra (standard dose)

• Registration Number: NCT01936844
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-03
• Study First Submitted QC: 2013-09-03
• Study First Posted: 2013-09-06
• Study Start: 2014-02
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Results First Submitted: 2016-01-15
• Results First Submitted QC: 2016-02-19
• Status Verified: 2016-03
• Results First Posted: 2016-03-22
• Last Update Submitted: 2016-03-31
• Last Update Posted: 2016-05-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anakinra (short)	Anakinra (high dose)	Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14
Placebo	Placebo	Placebo injections twice daily for the first 3 days then once daily for days 4-14.
Anakinra (short)	Anakinra (standard dose)	Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14

Primary Outcome Measures

Name	Time	Method
C Reactive Protein	3 days	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"

Secondary Outcome Measures

Name	Time	Method
Left Ventricular Ejection Fraction	14 days	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%.
Brachial Artery Vasoreactivity	14 days	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.

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States