Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01542502
• Collaborator: American Heart Association (Other)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This will be a randomized, double-blind, crossover pilot study to measure the safety and feasibility of Interleukin-1 (IL-1) blockade with Anakinra in patients with stable heart failure with preserved ejection fraction.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Anakinra; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anakinra Treatment with daily subcutaneous injections of Anakinra 100 mg	Drug: Anakinra; Anakinra 100 mg daily subcutaneous injection; Other Names: Recombinant human Interleukin-1 receptor antagonist Kineret
Placebo Comparator: Placebo Treatment with daily subcutaneous injection of placebo	Drug: Placebo; Placebo daily subcutaneous injection; Other Names: Sodium Chloride (NaCl) 0.9%

Outcome Measures

Primary Outcome Measures

1. Peak Oxygen Consumption (Peak VO2) [14 days]

   The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 12) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous).

Secondary Outcome Measures

1. Exercise Time [14 days]

   Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment

Other Outcome Measures

1. Correlation Between Endpoints [28 days]

   Correlation between interval change in peak VO2 and high sensitivity C-reactive protein

2. Heart Failure Symptoms (DASI) [28 days]

   Interval change from baseline in Heart Failure (HF) symptoms as measured by Duke Activity Status Index (DASI) upon completion of 2 weeks treatment.

3. Adverse Events [28 days]

   Additional endpoints will include assessment of adverse events and hospitalizations during 4-week duration of study.

4. Inflammatory Biomarkers [28 days]

   Interval change from baseline in high-sensitivity C-reactive protein upon completion of 2 weeks treatment.

5. Ventilatory Efficiency (VE/VCO2 [Carbon Dioxide] Slope) [14 days]

   Interval change from baseline in ventilatory efficiency (VE/VCO2 slope) upon completion of 2 weeks treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Symptoms and signs of congestive heart failure

• Recent Imaging Study (<12 months) showing Left Ventricular Ejection Fraction (LVEF)

50% and Left Ventricular End Diastolic Volume Index (LVEDVI) <97ml/m2

• Evidence of abnormal Left Ventricular (LV) relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following:

1. Invasive Hemodynamic measurements

• mean Pulmonary Capillary Wedge pressure (mPCW) >12

• Left Ventricular End Diastolic Pressure (LVEDP) >16 mmHg

1. Tissue Doppler Echocardiogram

• E/E' >15

• E/E' 8-15 and one of the following

• Left Ventricular Hypertrophy (LVH)

• Atrial Fibrillation

• Left Atrial Enlargement

• E/A <0.5 + Deceleration Time (DT) >280 (if >50yrs of age)

1. Biomarkers

• Brain Natriuretic Peptide (BNP) >200pg/mL

Exclusion Criteria:

• Age <18

• 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 Heart Failure (HF) or acute decompensated HF within the previous 12months

• 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

• Active infection including chronic infection

• Active cancer

• Recent (<14 days) use of anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]), Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, or any comorbidity limiting survival or ability to complete the study

• Pregnancy (determined by urine pregnancy test in women of childbearing potential)

• Inability to give informed consent

• Other conditions limiting completion of cardiopulmonary exercise test or completion of the study

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
• American Heart Association

Investigators

• Principal Investigator: Antonio Abbate, MD, PhD, Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT01542502
• Other Study ID Numbers: HM14079
• First Posted: Mar 2, 2012
• Last Update Posted: Feb 6, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Virginia Commonwealth University: Heart failure with preserved ejection fraction; Diastolic heart failure; Aerobic exercise performance
• Additional relevant MeSH terms: Heart Failure; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Arm/Group Title	Anakinra (First) Then Placebo (Second)	Placebo (First) Then Anakinra (Second)
Arm/Group Description	Treatment with daily subcutaneous injections of Anakinra 100 mg for 14 days, followed by daily subcutaneous injections of Placebo for 14 days Anakinra: Anakinra 100 mg daily subcutaneous injection Placebo: Placebo daily subcutaneous injection	Treatment with daily subcutaneous injections of Placebo for 14 days, followed by daily subcutaneous injections of Anakinra for 14 days Placebo: Placebo daily subcutaneous injection Anakinra: Anakinra 100 mg daily subcutaneous injection
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Baseline measures for all study participants
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 91.7%
>=65 years	1 8.3%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	61
Gender (Count of Participants)
Female	11 91.7%
Male	1 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Peak Oxygen Consumption (Peak VO2)
Description	The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 12) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	Treatment with daily subcutaneous injections of Anakinra 100 mg Anakinra: Anakinra 100 mg daily subcutaneous injection	Treatment with daily subcutaneous injection of placebo Placebo: Placebo daily subcutaneous injection
Measure Participants	12	12
Median (Inter-Quartile Range) [ml*kg^-1*min^-1]	1.1	-0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anakinra, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Exercise Time
Description	Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	Treatment with daily subcutaneous injections of Anakinra Anakinra: Anakinra 100 mg daily subcutaneous injection	Treatment with daily subcutaneous injection of placebo Placebo: Placebo daily subcutaneous injection
Measure Participants	12	12
Median (Inter-Quartile Range) [minutes]	0.05	0.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anakinra, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	ANOVA
	Comments

3. Other Pre-specified Outcome

Title	Correlation Between Endpoints
Description	Correlation between interval change in peak VO2 and high sensitivity C-reactive protein
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Heart Failure Symptoms (DASI)
Description	Interval change from baseline in Heart Failure (HF) symptoms as measured by Duke Activity Status Index (DASI) upon completion of 2 weeks treatment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Adverse Events
Description	Additional endpoints will include assessment of adverse events and hospitalizations during 4-week duration of study.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Inflammatory Biomarkers
Description	Interval change from baseline in high-sensitivity C-reactive protein upon completion of 2 weeks treatment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Ventilatory Efficiency (VE/VCO2 [Carbon Dioxide] Slope)
Description	Interval change from baseline in ventilatory efficiency (VE/VCO2 slope) upon completion of 2 weeks treatment.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	28 days
Arm/Group Title	Anakinra		Placebo
Arm/Group Description	Treatment with daily subcutaneous injections of Anakinra 100 mg Anakinra: Anakinra 100 mg daily subcutaneous injection		Treatment with daily subcutaneous injection of placebo Placebo: Placebo daily subcutaneous injection
All Cause Mortality
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Injection site reactions	3/12 (25%)		0/12 (0%)

Limitations/Caveats

This is a pilot study to estimate the effects of targeted anti-inflammatory treatment on aerobic exercise capacity in patients with Heart Failure and Preserved Ejection Fraction. All findings should therefore be considered hypothesis generating.

More Information

Certain Agreements

All Principal Investigators ARE 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.