VCU-ART: Anakinra to Prevent Post-infarction Remodeling

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00789724
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Thousands of patients die daily from early and late complications of a heart attack (acute myocardial infarction, AMI). Patients surviving AMI remain at high risk of death from adverse cardiac remodeling (dysfunction and enlargement of the heart) leading to heart failure (weakening of the heart).

Current interventions proven to reduce adverse remodeling and progression to heart failure include early reperfusion (restoring blood flow to the heart muscle) and long-term use of medicines that block the effects of hormones (such as angiotensin II, norepinephrine and aldosterone) involved in adverse remodeling. Despite these treatments, however, many patients continue to develop heart failure within 1 year of AMI. These patients are at very high risk of death.

Numerous changes occur in the hearts of patients after AMI that lead to adverse remodeling. Ischemia (lack of oxygen) and infarction (cell damage) lead to increased interleukin-1 (IL-1) production in the heart. IL-1 plays a critical role in adverse cardiac remodeling by coordinating the inflammatory pathway (leading to wound healing) and apoptotic pathway (leading to cell death).

In opposition to IL-1 activity, the human body produces a natural IL-1 receptor antagonist that blocks the effects of IL-1. The drug form of this IL-1 receptor antagonist (anakinra) is currently FDA approved for the treatment of rheumatoid arthritis, an inflammatory disease characterized by excessive IL-1 activity. Experimental studies show that anakinra is able to prevent cardiac remodeling and improve survival in mice after AMI.

We hypothesize that anakinra will show similar benefits in human patients by preventing adverse remodeling and heart failure after AMI.

Condition or Disease	Intervention/Treatment	Phase
ST Segment Elevation Acute Myocardial Infarction	Drug: Anakinra; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Recombinant Human Interleukin-1 Receptor Antagonist, Anakinra, to Prevent Post-infarction Remodeling: the Virginia Commonwealth University Anakinra Remodeling Trial (VCU-ART)
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anakinra Anakinra 100 mg given daily by subcutaneous injection for 14 days	Drug: Anakinra; 100 mg daily subcutaneous injection for 14 days; Other Names: Kineret (TM)
Placebo Comparator: Placebo 0.67 ml of NaCl 0.9% solution	Drug: Placebo; 0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

Outcome Measures

Primary Outcome Measures

1. Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging. [10-14 weeks]

Other Outcome Measures

1. Difference Between the 2 Arms in the Percentage of Patients With Any of the Following : a) End-systolic or End-diastolic Volume Index Increase >10%; b) Ejection Fraction Decrease >10%; c) E/E'>15 at Follow up [10-14 weeks]

2. Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam [10-14 weeks]

3. Difference Between the 2 Arms in Change in Serum BNP Levels, C-reactive Protein, and Hemoglobin A1c% From Baseline to Follow up [10-14 weeks]

4. Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase [48 hours]

5. Difference Between the 2 Arms in the Number of Adverse Effects Including a) All Events; b) All Events Requiring Unblinding of the Treatment; c) All Events Requiring Early Termination of the Intervention [10-14 weeks]

6. Difference Between the 2 Arms in Change in Oxygen Uptake Kinetics From Baseline to Follow up Exam at Submaximal Cardiopulmonary Exercise Test [10-14 weeks]

7. Difference Between the 2 Arms in Change in E/E' Ratios and Myocardial Performance (Tei) Indices From Baseline to Follow up Exam at Transthoracic Echo-color-Doppler Cardiac Exam [10-14 weeks]

8. Difference Between the 2 Arms in Change in End-diastolic Volume Indices and Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging [10-14 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age >18 years

• Acute (<24 hours) onset of chest pain

• New or presumably new ST elevation on ECG

• Planned coronary angiography for percutaneous revascularization

Exclusion Criteria:

• Inability to give informed consent

• Late presentation (>24 hours)

• Unsuccessful revascularization or urgent coronary bypass surgery

• Hemodynamic instability

• End-stage congestive heart failure (AHA/ACC stage C/D, NYHA class IV)

• Preexisting severe LV dysfunction (LVEF<20%) or severe valvular disease

• Severe asthma

• Pregnancy ( pre-enrollment pregnancy test)

• Contraindications to cardiac MRI or cardiac angiography

• Severe coagulopathy (INR>2.0, Platelet count<50,000/mm3)

• Severe renal insufficiency (creatinine clearance <30 ml/min/m2)

• Recent (<14 days) use of anti-inflammatory drugs (NSAIDS excluded)

• Chronic inflammatory disease

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT00789724
• Other Study ID Numbers: VCU-ART
• First Posted: Nov 13, 2008
• Last Update Posted: Nov 30, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Virginia Commonwealth University: acute myocardial infarction
• Additional relevant MeSH terms: Myocardial Infarction; Infarction; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Recruitment Details	Enrollment started in November 2008. During the first 4 months, 33 patients admitted with STEMI were screened and 10 patients were enrolled. One patient withdrew consent to the study on day 2 prior to all assessment and was excluded. The Institutional Review Board then approved enrollment of an additional patient who was enrolled in May 2009.

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	Anakinra 100 mg given daily by subcutaneous injection for 14 days	0.67 ml of NaCl 0.9% solution
Period Title: Overall Study
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Anakinra	Placebo	Total
Arm/Group Description	Anakinra 100 mg given daily by subcutaneous injection for 14 days	0.67 ml of NaCl 0.9% solution	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (13)	52 (15)	48 (13)
Sex: Female, Male (Count of Participants)
Female	2 40%	0 0%	2 20%
Male	3 60%	5 100%	8 80%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging.
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anakinra	Placebo
Arm/Group Description	Anakinra 100 mg given daily by subcutaneous injection for 14 days	0.67 ml of NaCl 0.9% solution
Measure Participants	5	5
Median (Inter-Quartile Range) [mL/m2]	-3.2	2.0

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	0.033
	Comments
	Method	ANOVA
	Comments

2. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in the Percentage of Patients With Any of the Following : a) End-systolic or End-diastolic Volume Index Increase >10%; b) Ejection Fraction Decrease >10%; c) E/E'>15 at Follow up
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in Change in Serum BNP Levels, C-reactive Protein, and Hemoglobin A1c% From Baseline to Follow up
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in the Number of Adverse Effects Including a) All Events; b) All Events Requiring Unblinding of the Treatment; c) All Events Requiring Early Termination of the Intervention
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in Change in Oxygen Uptake Kinetics From Baseline to Follow up Exam at Submaximal Cardiopulmonary Exercise Test
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in Change in E/E' Ratios and Myocardial Performance (Tei) Indices From Baseline to Follow up Exam at Transthoracic Echo-color-Doppler Cardiac Exam
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Difference Between the 2 Arms in Change in End-diastolic Volume Indices and Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging
Time Frame	10-14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	3 months
Arm/Group Title	Anakinra		Placebo
Arm/Group Description	Anakinra 100 mg given daily by subcutaneous injection for 14 days		0.67 ml of NaCl 0.9% solution
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	2/5 (40%)		4/5 (80%)
Cardiac disorders
Recurrent acute coronary syndrome	2/5 (40%)	2	2/5 (40%)	2
Congestive Heart Failure	0/5 (0%)	0	2/5 (40%)	2
Other (Not Including Serious) Adverse Events
	Anakinra		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Injection site pain	2/5 (40%)	2	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

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.