Trial Outcomes & Findings for Interleukin-1 Blockade in HF With Preserved EF (NCT NCT02173548)

NCT ID: NCT02173548

Last Updated: 2018-06-19

Results Overview

Absolute changes in aerobic exercise capacity (peak VO2) after 12 weeks treatment. This will compare patients treated with anakinra and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2018-06-19

Participant Flow

Participant milestones

Measure	Anakinra Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo Matching Placebo Placebo
Overall Study STARTED	21	10
Overall Study COMPLETED	20	8
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Anakinra Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo Matching Placebo Placebo
Overall Study Lost to Follow-up	0	2
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Interleukin-1 Blockade in HF With Preserved EF

Baseline characteristics by cohort

Measure	Anakinra n=21 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=10 Participants Matching Placebo Placebo	Total n=31 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	21 Participants n=5 Participants	10 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	10 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Absolute changes in aerobic exercise capacity (peak VO2) after 12 weeks treatment. This will compare patients treated with anakinra and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Change in Aerobic Exercise Capacity	-0.2 ml/kg/min Interval -0.9 to 1.7	1.0 ml/kg/min Interval -1.3 to 2.0

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Absolute changes in ventilatory efficiency (VE/VCO2 [carbon dioxide] slope) after 12 weeks treatment. This will compare patients treated with anakinra vs placebo, and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Change in Ventilatory Eefficiency	0.2 VE/VO2 slope Interval -2.1 to 1.8	-0.2 VE/VO2 slope Interval -1.6 to 1.3

SECONDARY outcome

Timeframe: 12 weeks

Structural and functional echocardiographic parameters include left and right ventricular dimensions, mass, systolic and diastolic function. (Change in e')

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Echocardiographic Assessment of Diastolic and Systolic Function (Left Ventricular Ejection Fraction)	0.3 cm/second Interval -0.8 to 1.0	1.9 cm/second Interval -0.3 to 4.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data not available for all participants.

Exercise stress echocardiography will be performed at baseline and 12 weeks to measure diastolic and contractile reserve. We will perform an assessment before initiation of exercise and immediately after cessation of peak exercise.

Outcome measures

Measure	Anakinra n=8 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=3 Participants Matching Placebo Placebo
Change in Diastolic and Contractile Reserve (e' Velocity and E/e' Ratio)	-0.7 ratio Interval -5.7 to 3.1	0.7 ratio Interval -4.5 to 0.7

SECONDARY outcome

Timeframe: Baseline to 12 weeks

The change C reactive protein (CRP) levels will be reported at 12 weeks. Higher C reactive protein levels indicate greater inflammation.

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Change in Inflammation (C Reactive Protein Levels)	-2.8 mg/l Interval -7.5 to -0.5	1.2 mg/l Interval -1.2 to 2.4

SECONDARY outcome

Timeframe: Baseline to 24 weeks

The Minnesota Living with Heart Failure questionnaire (MLWHF) is a 21-question graded questionnaire that has been extensively used to measure impairment in quality of life in patients with HF, with higher scores reflecting increased burden of HF symptoms. The questionnaire will be administered in accordance with cardiopulmonary test (CPET) and echocardiography. Scores range from zero to 105 with lower scores indicating better quality of life.

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Change in Quality of Life Questionnaire-Minnesota Living With Heart Failure Questionnaire (MLWHF)	-6 units on MWLHF scale Interval -19.0 to 1.0	-16 units on MWLHF scale Interval -24.0 to -11.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Two independent questionnaires will be used to assess quality of life and HF symptoms. The Duke Activity Status Index (DASI) questionnaire is a 12-question, yes/no, instrument that allows for the calculation of perceived functional capacity, in which each question describes a different physical activity and the questions are weighted according to their degree of physical exertion. Higher scores indicate greater functional capacity. The questionnaire will be administered at 0, 4, 12 and 24 weeks in accordance with cardiopulmonary test (CPET) and echocardiography. Scores range from zero to 58.2 with higher scores indicating higher functional status.

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Change in Quality of Life Questionnaire-Duke Activity Status Index (DASI)	4 units on DASI scale Interval -2.5 to 12.6	6.5 units on DASI scale Interval -6.6 to 11.4

SECONDARY outcome

Timeframe: 24 weeks

Number of participants admitted to hospital for acute decompensated heart failure

Outcome measures

Measure	Anakinra n=20 Participants Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=8 Participants Matching Placebo Placebo
Hospital Admission for Acute Decompensated Heart Failure	1 Participants	1 Participants

Adverse Events

Anakinra

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Anakinra n=20 participants at risk Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=10 participants at risk Matching Placebo Placebo
Cardiac disorders Acute decompensated heart failure	5.0% 1/20 • Number of events 1 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.	10.0% 1/10 • Number of events 1 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.

Other adverse events

Measure	Anakinra n=20 participants at risk Anakinra 100 mg given subcutaneously once daily for 12 weeks Anakinra	Placebo n=10 participants at risk Matching Placebo Placebo
Infections and infestations Upper respiratory infection	5.0% 1/20 • Number of events 1 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.	20.0% 2/10 • Number of events 2 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.
Infections and infestations Non serious infection	15.0% 3/20 • Number of events 3 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.	0.00% 0/10 • 24 weeks One participant in the anakinra arm withdrew from the study before receiving any study-related interventions.

Additional Information

Antonio Abbate, MD, PhD

Virginia Commonwealth University

Phone: (804) 828-0513

Email: antonio.abbate@vcuhealth.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place