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

NCT01936844 | Completed Phase 2 Results DMC

• 1 other identifier: VCU HM15347
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Left Ventricular Ejection Fraction

  14 days

• Brachial Artery Vasoreactivity

  14 days

Study Arms (2)

Anakinra (short)

EXPERIMENTAL

Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14

Drug: Anakinra (high dose); Drug: Anakinra (standard dose)

Placebo

PLACEBO COMPARATOR

Placebo injections twice daily for the first 3 days then once daily for days 4-14.

Drug: Placebo

Interventions

Anakinra (high dose) DRUG

Anakinra 100 mg daily twice daily for days 1, 2, and 3

Anakinra (short)

Anakinra (standard dose) DRUG

Anakinra 100 mg daily for days 4-14

Anakinra (short)

Placebo DRUG

Placebo twice daily for days 1, 2, and 3

Placebo

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All 5 criteria need to be met for enrollment of the patient in the study
• Primary diagnosis of acute decompensated heart failure within the last 24 hours as evidenced by both of the following:
• dyspnea or respiratory distress or tachypnea at rest or with minimal exertion
• 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.
• Left ventricular systolic dysfunction (LVEF\<40%) during index hospitalization or prior 12 months.
• Age ≥18 years old
• Willing and able to provide written informed consent.
• Screening plasma C-reactive protein levels \>5 mg/L.

You may not qualify if:

• The primary diagnosis for admission is NOT decompensated heart failure, including diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias.
• 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.
• Recent (previous 3 months) or planned cardiac resynchronization therapy (CRT), coronary artery revascularization procedures, or heart valve surgeries.
• Previous or planned implantation of left ventricular assist devices or heart-transplant.
• Chronic use of intravenous inotropes.
• Recent (\<14 days) use of immunosuppressive or anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs \[NSAIDs\]).
• Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus).
• Active infection (of any type);
• Chronic/recurrent infectious disease (including Hepatitis B virus \[HBV\], Hepatitis C virus \[HCV\], and HIV/AIDS).
• Prior (within the past 10 years) or current malignancy.
• Any comorbidity limiting survival or ability to complete the study.
• End stage kidney disease requiring renal replacement therapy.
• Neutropenia (\<2,000/mm3) or Thrombocytopenia (\<50,000/mm3).
• Pregnancy.
• Angina, arrhythmias, or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing obtained during the baseline testing.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• American Heart Association: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Benjamin Van Tassell, PharmD
• Organization: Virginia Commonwealth University

bvantassell@vcu.edu

8048284583

Study Officials

• Benjamin W Van Tassell, PharmD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: September 3, 2013
• First Posted: September 6, 2013
• Study Start: February 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 5, 2016
• Results First Posted: March 22, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)