Clinical trial NCT01936844: Interleukin (IL)-1 Blockade in Acute Heart Failure (Anakinra ADHF)
Official title: Interleukin-1 Blockade in Acute Decompensated Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2013-09-06
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: C Reactive Protein
timeFrame: 3 days
Secondary outcomes:
measure: Left Ventricular Ejection Fraction
timeFrame: 14 days
measure: Brachial Artery Vasoreactivity
timeFrame: 14 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Benjamin W Van Tassell, PharmD
role: PRINCIPAL_INVESTIGATOR
References: