Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01300650
• Collaborator: National Institutes of Health (NIH) (NIH), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 5.9
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This is an open-label, non-randomized, pilot-study to evaluate the effect of Interleukin-1 blockade on exercise capacity in patients with heart failure. Subjects will undergo cardiopulmonary exercise testing at baseline and after 2-weeks treatment with anakinra (recombinant human Interleukin-1 receptor antagonist).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Anakinra	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anakinra	Drug: Anakinra; Anakinra 100 mg subcutaneous injection daily

Outcome Measures

Primary Outcome Measures

1. Median Interval Change From Baseline in Peak VO2 [14 days]

   Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight. The outcome measure time frame was 14 days. This means that change in peak VO2 was calculated as the difference between peak VO2 at baseline and 14 days. To calculate this change, we used the mathematical process of subtraction (change in peak VO2 = Peak VO2 [day 14] - Peak VO2 [baseline])

2. Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) [14 days]

   The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless. Change in VE/VCO2 slope was calculated as the change in VE/VCO2 slope between baseline and 14 days. We therefore calculated the difference between VE/VCO2 slope measurements that occurred at baseline and at 14 days (change in VE/VCO2 slope = VE/VCO2 slope [day 14] - VE/VCO2 slope [baseline])

Secondary Outcome Measures

1. Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI) [14 days]

   The Duke Activity Status Index (DASI) is a scale that quantifies patients' ability to perform various tasks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores reflect improved activity or improved heart failure symptoms. Lower scores reflect worsened ability or worsened heart failure symptoms.

Other Outcome Measures

1. Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide) [14 days]

2. Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2 [14 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed diagnosis of heart failure

• Recent echocardiogram documenting left ventricular ejection fraction <40%

• High sensitivity C-reactive protein >2 mg/L.

Exclusion Criteria:

• Recent changes (previous 3 months) in HF maintenance medications (beta-blockers, angiotensin converting enzyme [ACE] inhibitors, aldosterone antagonists, vasodilators, cardiac glycosides, diuretics)

• Hospitalization for worsening HF or acute decompensated HF within the previous 12 months

• Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable cardioverter defibrillator (AICD)

• Angina or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing or baseline ECG changes that limit the ability to detect ischemia (i.e. left bundle-branch block).

• Recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs), chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, active infection, or any comorbidity limiting survival or ability to complete the study

• Severe kidney dysfunction (eGFR <30 mL/min)

• Coagulopathy (INR >1.5), thrombocytopenia (<50,000/mm3), or leukopenia (absolute neutrophil count <1,500/mm3)

• Pregnancy (female patients will be required to take a urine pregnancy test)

• Latex or rubber allergy

• Inability to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• National Institutes of Health (NIH)
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Benjamin W Van Tassell, PharmD, Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT01300650
• Other Study ID Numbers: AIR-HF Pilot Study; 1KL2RR031989-01
• First Posted: Feb 21, 2011
• Last Update Posted: Nov 30, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Virginia Commonwealth University: Heart failure; Inflammation; Interleukin-1; Cardiopulmonary exercise
• Additional relevant MeSH terms: Heart Failure; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Recruitment Details	11 patients had elevated hsCRP (>2 mg/L) and were enrolled in the study.
Pre-assignment Detail	2 patients withdrew consent prior to beginning the study. 1 patient underwent a change in heart failure medication prior to beginning the study and was therefore withdrawn from the study. The 8 remaining patients began the study interventions.

Arm/Group Title	Anakinra
Arm/Group Description	Anakinra 100 mg subcutaneous daily injection
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Anakinra
Arm/Group Description
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 87.5%
>=65 years	1 12.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (11)
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Median Interval Change From Baseline in Peak VO2
Description	Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight. The outcome measure time frame was 14 days. This means that change in peak VO2 was calculated as the difference between peak VO2 at baseline and 14 days. To calculate this change, we used the mathematical process of subtraction (change in peak VO2 = Peak VO2 [day 14] - Peak VO2 [baseline])
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra
Arm/Group Description	Anakinra 100 mg subcutaneous daily injection
Measure Participants	7
Median (Inter-Quartile Range) [mL/kg/min]	3.90

2. Primary Outcome

Title	Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
Description	The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless. Change in VE/VCO2 slope was calculated as the change in VE/VCO2 slope between baseline and 14 days. We therefore calculated the difference between VE/VCO2 slope measurements that occurred at baseline and at 14 days (change in VE/VCO2 slope = VE/VCO2 slope [day 14] - VE/VCO2 slope [baseline])
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra
Arm/Group Description	Anakinra 100 mg subcutaneous daily injection
Measure Participants	7
Median (Inter-Quartile Range) [(unitless)]	-2.10

3. Secondary Outcome

Title	Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
Description	The Duke Activity Status Index (DASI) is a scale that quantifies patients' ability to perform various tasks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores reflect improved activity or improved heart failure symptoms. Lower scores reflect worsened ability or worsened heart failure symptoms.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra
Arm/Group Description	Anakinra 100 mg subcutaneous injection
Measure Participants	7
Median (Inter-Quartile Range) [units on a scale]	6

4. Other Pre-specified Outcome

Title	Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Anakinra
Arm/Group Description
All Cause Mortality
	Anakinra
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Anakinra
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Anakinra
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
General disorders
Flu-like symptoms	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.