Treatment of Acute Pericarditis With Anakinra

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03224585
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Actual Duration (Months): 20.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of this study is to determine the safety and efficacy of anakinra for the treatment of acute pericarditis when initiated within 6 hours of diagnosis and continued for 3 or 7 days.

1. to determine the efficacy of anakinra with respect to chest pain resolution

2. to determine the safety of anakinra with respect to adverse drug events

Condition or Disease	Intervention/Treatment	Phase
Acute Pericarditis	Drug: Anakinra; Drug: Placebo	Phase 2

Detailed Description

Acute pericarditis is a clinical syndrome characterized by a profound inflammation of the membrane tissue that surrounds, supports and protects the heart. Acute pericarditis can be caused by a variety of infectious and non-infectious agents, but it most commonly either follows a viral infection of the upper respiratory tract or has no apparent cause.

Acute pericarditis occurs rather abruptly in previously healthy individuals, generally a child or young adult. Most cases of acute pericarditis resolve within a few days with non-steroidal anti-inflammatory drugs. However, patients experience severe chest pain and are at high risk for life-threatening complications involving the pericardium, such as pericardial tamponade. Acute pericarditis is diagnosed in 1 in 20 (5%) ED visits for chest pain.

Anakinra (Kineret) has been shown to treat and cure refractory and recurrent pericarditis. This study is aimed at determining whether anakinra is also effective as first line treatment in acute pericarditis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Acute Pericarditis With Anakinra
• Actual Study Start Date: May 11, 2018
• Actual Primary Completion Date: Feb 1, 2020
• Actual Study Completion Date: Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anakinra 100 mg subcutaneous injection	Drug: Anakinra; Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - anakinra 100 mg subcutaneous injections daily for 4 days
Placebo Comparator: Placebo 100 mg NaCl 0.9% subcutaneous injection	Drug: Placebo; Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - placebo 100 mg saline subcutaneous injections daily for 4 days

Outcome Measures

Primary Outcome Measures

1. Pain Score [Baseline to 6 hours]

   Change from baseline in visual analog pain score from 0 to 10. For this visual analog pain scale, the patient is asked to rate their pain from 0 to 10. A score of 0 represents "no pain", a score of 5 represents "moderate pain", and 10 represents "worst pain".

Secondary Outcome Measures

1. Pain Score [Baseline to 24 hours]

   Change from baseline in visual analog pain score from 0 to 10. For this visual analog pain scale, the patient is asked to rate their pain from 0 to 10. A score of 0 represents "no pain", a score of 5 represents "moderate pain", and 10 represents "worst pain".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥12 years in presence of a parent able to provide consent or age >18 years

• First or recurrent episode of acute pericarditis, defined as the presence of at least 2 of the following:

• Chest pain (suggestive of pericarditis and not explained by another condition)

• Pericardial friction rub on physical exam

• ST-segment elevation and/or PR depression on ECG

• New or worsening pericardial effusion

• Pain of moderate-to-severe intensity (pain score ≥6 on a scale of 0-10 where 0 is no pain at all and 10 is the worst pain ever experienced) at time on enrollment

• Ability to provide written informed consent if 18 years or older or to provide assent in presence of parental consent if 12-17 years of age

Exclusion Criteria:

• Pericarditis due to known bacterial or fungal infection

• Pericarditis due to known malignancy

• Pericarditis after cardiac surgery

• Tamponade or need for pericardiocentesis for diagnostic/therapeutic purposes

• Pregnancy or breastfeeding

• Hypersensitivity to anakinra, latex or products derived from Escherichia coli

• Chronic pain syndrome or chronic use of analgesic drugs

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, PhD, Virginia Commonwealth University

Study Documents (Full-Text)

• Informed Consent Form - Jun 8, 2017
• Study Protocol - Jun 8, 2017
• Statistical Analysis Plan - Jun 8, 2017

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT03224585
• Other Study ID Numbers: HM20008638
• First Posted: Jul 21, 2017
• Last Update Posted: Feb 23, 2021
• Last Verified: Feb 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Virginia Commonwealth University: anakinra; Kineret; pericarditis
• Additional relevant MeSH terms: Pericarditis; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Arm/Group Title	Anakinra (3 Days) Then Anakinra (4 Days)	Anakinra (3 Days) Then Placebo (4 Days)
Arm/Group Description	Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - anakinra 100 mg subcutaneous injections daily for 4 days	Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - placebo 100 mg saline subcutaneous injections daily for 4 days
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Anakinra (3 Days) Then Anakinra (4 Days)	Anakinra (3 Days) Then Placebo (4 Days)	Total
Arm/Group Description	100 mg subcutaneous injection Anakinra: Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - anakinra 100 mg subcutaneous injections daily for 4 days	100 mg NaCl 0.9% subcutaneous injection Placebo: Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - placebo 100 mg saline subcutaneous injections daily for 4 days	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (9)	40 (16)	41 (12)
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 20%
Male	1 50%	3 100%	4 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 50%	1 33.3%	2 40%
White	1 50%	2 66.7%	3 60%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Pain Score
Description	Change from baseline in visual analog pain score from 0 to 10. For this visual analog pain scale, the patient is asked to rate their pain from 0 to 10. A score of 0 represents "no pain", a score of 5 represents "moderate pain", and 10 represents "worst pain".
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	This group includes all patients enrolled in the clinical trial
Measure Participants	5
Median (Inter-Quartile Range) [units on a scale]	-3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Patients
	Comments	This analysis compared the change in pain scores between baseline and 6 hours
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0121
	Comments
	Method	Paired samples Wilcoxon test
	Comments

2. Secondary Outcome

Title	Pain Score
Description	Change from baseline in visual analog pain score from 0 to 10. For this visual analog pain scale, the patient is asked to rate their pain from 0 to 10. A score of 0 represents "no pain", a score of 5 represents "moderate pain", and 10 represents "worst pain".
Time Frame	Baseline to 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	This group includes all patients enrolled in the clinical trial
Measure Participants	5
Median (Inter-Quartile Range) [units on a scale]	-4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Patients
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	Paired samples Wilcoxon test
	Comments

Adverse Events

Time Frame	30 days
Adverse Event Reporting Description	Adverse events assessed via daily physician examination and routine labs
Arm/Group Title	Anakinra (3 Days) Then Anakinra (4 Days)		Anakinra (3 Days) Then Placebo (4 Days)
Arm/Group Description	Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - anakinra 100 mg subcutaneous injections daily for 4 days		Period 1 (Time 0-72 hours) - this will be an open-label phase during which all subjects meeting enrollment criteria will receive anakinra 100 mg subcutaneously injections daily for 3 days. Period 2 (Time 72 hours to 7 days) - placebo 100 mg saline subcutaneous injections daily for 4 days
All Cause Mortality
	Anakinra (3 Days) Then Anakinra (4 Days)		Anakinra (3 Days) Then Placebo (4 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Serious Adverse Events
	Anakinra (3 Days) Then Anakinra (4 Days)		Anakinra (3 Days) Then Placebo (4 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		3/3 (100%)
Cardiac disorders
Coronary vasospasm - After completion of anakinra	0/2 (0%)	0	1/3 (33.3%)	1
Resistant pericarditis - After completion of anakinra	0/2 (0%)	0	1/3 (33.3%)	1
Vascular disorders
Thrombophlebitis - After completion of anakinra	0/2 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Anakinra (3 Days) Then Anakinra (4 Days)		Anakinra (3 Days) Then Placebo (4 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Injection site reactions - While taking anakinra	1/2 (50%)	1	1/3 (33.3%)	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.