Trial Outcomes & Findings for Interleukin (IL)-1 Blockade in Acute Heart Failure (Anakinra ADHF) (NCT NCT01936844)

Results Overview

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"

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

30 participants

Primary outcome timeframe

3 days

Results posted on

2016-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	Anakinra (Short) Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
Overall Study STARTED	15	15
Overall Study COMPLETED	9	8
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anakinra (Short) n=15 Participants Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=15 Participants Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	60 years n=5 Participants	54 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
C-reactive protein	22.3 mg/L n=5 Participants	27.4 mg/L n=7 Participants	23.8 mg/L n=5 Participants

PRIMARY outcome

Timeframe: 3 days

Population: 1 patient in each group withdrew from the study prior to collection of data for the primary endpoint.

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"

Outcome measures

Outcome measures
Measure	Anakinra (Short) n=14 Participants Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=14 Participants Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
C Reactive Protein	2.09 days Interval 1.73 to 2.61	2.93 days Interval 2.36 to 3.79

SECONDARY outcome

Timeframe: 14 days

Population: Some patients did not undergo LVEF assessment at 14 days because they did not show up to their scheduled appointment.

Change in left ventricular ejection fraction (LVEF) between admission and 14 day follow up. This value is expressed as absolute change in measured LVEF. For example, if baseline LVEF = 20% and 14 day LVEF = 25%, this would be reported as an absolute change of 5%.

Outcome measures

Outcome measures
Measure	Anakinra (Short) n=7 Participants Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=7 Participants Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
Left Ventricular Ejection Fraction	10 percent LVEF Interval 3.0 to 14.0	0 percent LVEF Interval -16.0 to 5.0

SECONDARY outcome

Timeframe: 14 days

Population: Some patients did not undergo assessment at 14 days because they did not show up to their scheduled appointment.

Change in flow mediated vasodilatation (FMD) of the brachial artery. Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. The change is FMD is reported as the % change in FMD from baseline to 14 days.

Outcome measures

Outcome measures
Measure	Anakinra (Short) n=8 Participants Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=7 Participants Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
Brachial Artery Vasoreactivity	41.7 percentage change Interval -44.5 to 98.2	-45.2 percentage change Interval -101.0 to 45.8

Adverse Events

Anakinra (Short)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anakinra (Short) n=15 participants at risk Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=15 participants at risk Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
Cardiac disorders Worsening heart failure or Readmission for heart failure	13.3% 2/15 • Number of events 2	20.0% 3/15 • Number of events 3
Infections and infestations Serious infection/sepsis	0.00% 0/15	6.7% 1/15 • Number of events 1

Other adverse events

Other adverse events
Measure	Anakinra (Short) n=15 participants at risk Anakinra 100 mg twice daily for the first 3 days followed by 100 mg daily for days 4-14 Anakinra (high dose): Anakinra 100 mg daily twice daily for days 1, 2, and 3 Anakinra (standard dose): Anakinra 100 mg daily for days 4-14	Placebo n=15 participants at risk Placebo injections twice daily for the first 3 days then once daily for days 4-14. Placebo: Placebo twice daily for days 1, 2, and 3 Placebo: Placebo daily for days 4-14
Renal and urinary disorders Acute kidney injury	26.7% 4/15 • Number of events 4	33.3% 5/15 • Number of events 5
Cardiac disorders Atrial fibrillation	0.00% 0/15	6.7% 1/15 • Number of events 1

Additional Information

Benjamin Van Tassell, PharmD

Virginia Commonwealth University

Phone: 8048284583

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place