Heart Failure
Conditions
Brief summary
The RED-HART is a randomized double-blinded placebo-controlled study of Anakinra (IL-1 blocker) in patients with recently decompensated heart failure to determine the safety and efficacy in terms of aerobic exercise capacity and ventilatory efficiency measured with a cardiopulmonary exercise test.
Interventions
DRUGAnakinra (weeks 1-2)
Anakinra 100 mg daily for weeks 1 and 2
DRUGAnakinra (weeks 3-12)
DRUGPlacebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
All 6 criteria need to be met for enrollment of the patient in the study 1. Primary diagnosis for hospitalization is decompensated heart failure established as the finding at admission of all 2 conditions listed below: 1. dyspnea or respiratory distress or tachypnea at rest or with minimal exertion; 2. evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met); * pulmonary congestion/edema at physical exam OR chest X-Ray; * plasma Brain Natriuretic Peptide (BNP) levels ≥200 pg/ml; * invasive measurement of left ventricular end-diastolic pressure \>18 mmHg or of pulmonary artery occluding pressure (wedge) \>16 mmHg. 2. The patient has a prior documentation of impaired left ventricular systolic function (ejection fraction \<50%) at most recent assessment by any imaging modality (within 12 months). 3. The patient is now clinically stable and meets standard criteria for hospital discharge as documented by all the 3 conditions listed below: 1. absence of dyspnea or pulmonary congestion/distress at rest; 2. absence of pitting edema in the lower extremities, or in any other region; 3. stable hemodynamic parameters (blood pressure, heart rate). 4. The patient is of age ≥21 years old, and is willing and able to provide written informed consent. 5. The patient is willing and able to comply with the protocol (i.e. self administration of the treatment, and exercise protocol). 6. The patient has screening plasma C-reactive protein levels \>2 mg/L.
Exclusion criteria
Subjects will not be eligible if they meet any of the following 15
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Interval Changes in Peak Oxygen Consumption (VO2) | Baseline to 2 weeks | Interval changes in peak oxygen consumption (VO2) after 2 weeks of anakinra treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Improvement | 12 weeks | The Duke Activity Status Index questionnaire will be completed at enrollment and 12 weeks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores represent increased ability to perform daily activities and may be interpreted as improved quality of life. |
| Death or Hospital Admission for Heart Failure | 24 weeks | We will monitor survival and hospitalization for heart failure throughout the 24 week follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anakinra (Short) Anakinra 100 mg daily for 2 weeks, followed by placebo for 10 weeks
Anakinra (weeks 1-2): Anakinra 100 mg daily for weeks 1 and 2 | 20 |
| Anakinra (Long) Anakinra 100 mg daily for 12 weeks
Anakinra (weeks 1-2): Anakinra 100 mg daily for weeks 1 and 2
Anakinra (weeks 3-12) | 20 |
| Placebo Placebo injections daily for 12 weeks
Placebo | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Anakinra (Long) | Placebo | Anakinra (Short) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 4 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 15 Participants | 16 Participants | 48 Participants |
| Age, Continuous | 53.5 years | 59.5 years | 55 years | 56.5 years |
| Region of Enrollment United States | 20 participants | 20 participants | 20 participants | 60 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 15 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 16 | 0 / 18 | 1 / 18 |
| other Total, other adverse events | 0 / 16 | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 7 / 16 | 3 / 18 | 7 / 18 |
Outcome results
Primary
Interval Changes in Peak Oxygen Consumption (VO2)
Interval changes in peak oxygen consumption (VO2) after 2 weeks of anakinra treatment.
Time frame: Baseline to 2 weeks
Population: Patients who completed baseline and 2 week exercise evaluation
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra (Short) | Interval Changes in Peak Oxygen Consumption (VO2) | Baseline | 14.05 mL/kg/min |
| Anakinra (Short) | Interval Changes in Peak Oxygen Consumption (VO2) | 2 weeks | 14.85 mL/kg/min |
| Anakinra (Long) | Interval Changes in Peak Oxygen Consumption (VO2) | Baseline | 14.45 mL/kg/min |
| Anakinra (Long) | Interval Changes in Peak Oxygen Consumption (VO2) | 2 weeks | 14.45 mL/kg/min |
| Placebo | Interval Changes in Peak Oxygen Consumption (VO2) | Baseline | 13.3 mL/kg/min |
| Placebo | Interval Changes in Peak Oxygen Consumption (VO2) | 2 weeks | 12.65 mL/kg/min |
Comparison: This test reflects a comparison between baseline and 2 weeks (both rows).p-value: >0.2ANOVA
Secondary
Death or Hospital Admission for Heart Failure
We will monitor survival and hospitalization for heart failure throughout the 24 week follow-up
Time frame: 24 weeks
Population: All analyses were restricted to patients with a minimum of 2 weeks follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anakinra (Short) | Death or Hospital Admission for Heart Failure | 4 participants |
| Anakinra (Long) | Death or Hospital Admission for Heart Failure | 1 participants |
| Placebo | Death or Hospital Admission for Heart Failure | 3 participants |
p-value: 0.12Log Rank
Secondary
Quality of Life Improvement
The Duke Activity Status Index questionnaire will be completed at enrollment and 12 weeks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores represent increased ability to perform daily activities and may be interpreted as improved quality of life.
Time frame: 12 weeks
Population: Patients with baseline and follow-up data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anakinra (Short) | Quality of Life Improvement | Baseline | 26.95 units on a scale |
| Anakinra (Short) | Quality of Life Improvement | 12 weeks | 37.575 units on a scale |
| Anakinra (Long) | Quality of Life Improvement | Baseline | 23.45 units on a scale |
| Anakinra (Long) | Quality of Life Improvement | 12 weeks | 34.45 units on a scale |
| Placebo | Quality of Life Improvement | Baseline | 22.825 units on a scale |
| Placebo | Quality of Life Improvement | 12 weeks | 28.7 units on a scale |
Comparison: Paired analysis versus baselinep-value: <0.01Wilcoxon (Mann-Whitney)