Cardiogenic Shock
Conditions
Keywords
Therapeutic Hypothermia (TH)
Brief summary
The purpose of the study is to compare patients with cardiogenic shock who receive standard therapy plus therapeutic hypothermia (TH) to patients with cardiogenic shock who receive standard medical therapy alone in order to assess the safety of TH in patients with cardiogenic shock. This study will also help understand the physiologic effects of TH in patients with cardiogenic shock. This will be a pilot study to establish the initial safety of TH and to assess tolerability of TH in this patient population.
Detailed description
This is an unblinded pilot study of 20 patients randomized to either TH plus standard medical care or to standard medical care alone. All patients will undergo pulmonary artery (PA) catheter placement as part of the standard of care for management of cardiogenic shock. Data from the PA catheter is vital in monitoring real-time hemodynamics, initiating vasopressors/inotropes, assessing the response to the therapies, and possible need for escalation of therapy. For patients randomized to TH, cooling to 32-34°C will then be initiated and maintained for 24 hours using the FDA-approved Intravascular Temperature Management (IVTM™) System with the 9.3 French Quattro® Catheter. The IVTM™ System along with the Quattro® Catheter are currently FDA-approved for use in cardiac surgery patients to achieve and maintain normothermia during surgery and in recovery and to induce, maintain, and reverse mild hypothermia in neurosurgery patients during surgery and in recovery. The IVTM™ System and Quattro® Catheter are not, however, currently FDA-approved to achieve therapeutic hypothermia in cardiogenic shock patients. TH is achieved by circulating normal saline in a closed system through the catheter. The temperature is measured and adjustments are made by the thermal regulation system to automatically maintain target temperature. The target temperature is achieved within 2-3 hours of initiation of TH. Rewarming is accomplished using the same balloon catheter system and heat exchange occurs without infusion of any saline or fluids. Standard medical therapy for all patients will be based on the current recommendations for management of cardiogenic shock. This includes inotropic therapy for cardiac support, vasopressor therapy to achieve target blood pressure, diuretics for volume removal, and mechanical circulatory support as clinically indicated. Laboratory, echocardiographic, and hemodynamic parameters will be obtained for patients prior to randomization, after 18-24 hours post-randomization, and after 48-96 hours post-randomization. Core temperature will be measured via either thermal tip at the end of a transurethral urinary catheter or endotracheal temperature probe in intubated patients.
Interventions
DEVICEIVTM™ System
TH will be initiated and maintained for 24 hours using the IVTM™ System and the Quattro® Catheter. After 24 hours of maintained TH, patients will be rewarmed to normal body temperature using the same Quattro® Catheter.
DEVICEQuattro® Catheter
TH will be initiated and maintained for 24 hours using the IVTM™ System and the Quattro® Catheter. After 24 hours of maintained TH, patients will be rewarmed to normal body temperature using the same Quattro® Catheter.
Sponsors
ZOLL Circulation, Inc., USA
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Cardiogenic shock 1. Systolic blood pressure \<90mmHg for at least 30 minutes 2. Cardiac Index \< 2.2 L/min/m2 3. Pulmonary capillary wedge pressure (PCWP) ≥ 15mmHg 4. Need for central venous access, vasopressors, inotropes and/or mechanical circulatory support (i.e. intra-aortic balloon pump, Impella®, ECMO) to maintain systolic blood pressure ≥ 90mmHg 2. Etiology of shock 1. Acute coronary syndromes (STEMI, NSTEMI, or UA) 2. Ischemic or non-ischemic cardiomyopathy 3. Myocarditis 4. Hypertrophic cardiomyopathy 5. Stress-induced cardiomyopathy 6. Peripartum cardiomyopathy 7. Cardiogenic shock in a patient with heart failure with preserved ejection fraction 3. Age ≥ 18 years AND ≤ 89 years 4. Admission to the University of Chicago Coronary Care Unit
Exclusion criteria
1. Baseline heart rate \< 60 beats per minute 2. Baseline temperatures \< 35°C 3. Recent cardiotomy 4. History of cardiac transplantation 5. Current pregnancy 6. Contraindication to 9.3 French femoral venous access for placement of intravascular cooling catheter 7. Hospice designation (either currently in hospice or previously enrolled within the past 30 days)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Episodes of Arrhythmia | up to 96 hours | requiring intervention (medical therapy or therapy with temporary pacemaker) |
| Number of Participants With Bleeding | up to 96 hours | requiring transfusions as a direct result of the cooling catheter insertion or secondary to resulting coagulopathy |
| Number of Participants With Bloodstream Infection/Suspected Sepsis | up to 96 hours | confirmed with 2 positive blood cultures or sequential organ failure assessment (SOFA) score \>2 |
| Number of Participants With Hypokalemia | up to 96 hours | potassium levels below 3.0mEq/L, not secondary to other identifiable causes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction | up to 18-24 hours | percent ejection fraction on echocardiogram at 18-24 hours after randomization |
| All-cause Mortality | up to 96 hours, 30 days, and 90 days | All-cause mortality at 90 days was primary outcome/time point of choice. |
| Changes in Cardiac Index | up to 96 hours | Difference between groups in cardiac index and output |
| Cumulative Dopamine Dose | 96 hours | Cumulative weight adjusted dopamine dose |
| Cumulative Dobutamine Dose | 96 hours | Cumulative dose of weight adjusted dobutamine dobutamine |
| Changes in Systemic Vascular Resistance (SVR) | up to 96 hours | Mean SVR in population |
| Cardiac Power Index | up to 96 hours | Measured 48-96 hours after randomization |
| Cumulative Milrinone Dose | up to 96 hours | cumulative weight adjusted dosing of milrinone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Patients will receive only standard of care treatment for cardiogenic shock. | 10 |
| Therapeutic Hypothermia Patients will be cooled to between 32°C and 34°C using the IVTM™ System and the Quattro® Catheter in addition to receiving standard of care treatment for cardiogenic shock.
IVTM™ System: TH will be initiated and maintained for 24 hours using the IVTM™ System and the Quattro® Catheter. After 24 hours of maintained TH, patients will be rewarmed to normal body temperature using the same Quattro® Catheter.
Quattro® Catheter: TH will be initiated and maintained for 24 hours using the IVTM™ System and the Quattro® Catheter. After 24 hours of maintained TH, patients will be rewarmed to normal body temperature using the same Quattro® Catheter. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | Control Group | Therapeutic Hypothermia |
|---|---|---|---|
| ACEi | 7 Participants | 5 Participants | 2 Participants |
| ACS | 5 Participants | 4 Participants | 1 Participants |
| Acute on Chronic ICM/NICM | 15 Participants | 7 Participants | 8 Participants |
| Admission NT-proBNP | 20858.1 pg/mL STANDARD_DEVIATION 19189.6 | 15056 pg/mL STANDARD_DEVIATION 11751.4 | 29561.3 pg/mL STANDARD_DEVIATION 26575.1 |
| Age, Continuous Age | 62.9 years STANDARD_DEVIATION 10.3 | 63.6 years STANDARD_DEVIATION 10.3 | 62.2 years STANDARD_DEVIATION 10.8 |
| Antiarrhythmic | 2 Participants | 1 Participants | 1 Participants |
| Anti-platelet agent | 6 Participants | 3 Participants | 3 Participants |
| ARB | 4 Participants | 1 Participants | 3 Participants |
| ASA | 16 Participants | 7 Participants | 9 Participants |
| Atrial fibrillation | 5 Participants | 3 Participants | 2 Participants |
| Baseline Creatinine | 2.2 mg/dL | 2.1 mg/dL | 2.7 mg/dL |
| Beta-blockers | 16 Participants | 9 Participants | 7 Participants |
| BMI (kg/mg) | 30.7 kg/m^2 STANDARD_DEVIATION 6 | 31.3 kg/m^2 STANDARD_DEVIATION 6.8 | 30.1 kg/m^2 STANDARD_DEVIATION 5.4 |
| CAD | 11 Participants | 5 Participants | 6 Participants |
| CVA | 5 Participants | 2 Participants | 3 Participants |
| Diuretic | 14 Participants | 7 Participants | 7 Participants |
| DM | 13 Participants | 7 Participants | 6 Participants |
| Ejection Fraction on initial TTE | 32.3 percentage of ejection fraction STANDARD_DEVIATION 17.4 | 30.3 percentage of ejection fraction STANDARD_DEVIATION 14.4 | 34 percentage of ejection fraction STANDARD_DEVIATION 20 |
| HTN | 20 Participants | 10 Participants | 10 Participants |
| IABP | 9 Participants | 6 Participants | 3 Participants |
| Inotropic support prior to enrollment | 2 Participants | 2 Participants | 0 Participants |
| Mechanical Circulatory Support prior to enrollment | 9 Participants | 6 Participants | 3 Participants |
| Mechanical Ventilation | 10 Participants | 7 Participants | 3 Participants |
| Neprilysin Inhibitor | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 14 Participants | 7 Participants | 7 Participants |
| Statin | 15 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 4 / 10 |
| other Total, other adverse events | 0 / 10 | 8 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 |
Outcome results
Primary
Number of Participants With Bleeding
requiring transfusions as a direct result of the cooling catheter insertion or secondary to resulting coagulopathy
Time frame: up to 96 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With Bleeding | 0 Participants |
| Therapeutic Hypothermia | Number of Participants With Bleeding | 2 Participants |
p-value: 0.47Fisher Exact
Primary
Number of Participants With Bloodstream Infection/Suspected Sepsis
confirmed with 2 positive blood cultures or sequential organ failure assessment (SOFA) score \>2
Time frame: up to 96 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With Bloodstream Infection/Suspected Sepsis | 0 Participants |
| Therapeutic Hypothermia | Number of Participants With Bloodstream Infection/Suspected Sepsis | 0 Participants |
p-value: 1Fisher Exact
Primary
Number of Participants With Episodes of Arrhythmia
requiring intervention (medical therapy or therapy with temporary pacemaker)
Time frame: up to 96 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With Episodes of Arrhythmia | 0 Participants |
| Therapeutic Hypothermia | Number of Participants With Episodes of Arrhythmia | 1 Participants |
p-value: 1Fisher Exact
Primary
Number of Participants With Hypokalemia
potassium levels below 3.0mEq/L, not secondary to other identifiable causes
Time frame: up to 96 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With Hypokalemia | 0 Participants |
| Therapeutic Hypothermia | Number of Participants With Hypokalemia | 0 Participants |
p-value: 1Fisher Exact
Secondary
All-cause Mortality
All-cause mortality at 90 days was primary outcome/time point of choice.
Time frame: up to 96 hours, 30 days, and 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | All-cause Mortality | 3 Participants |
| Therapeutic Hypothermia | All-cause Mortality | 4 Participants |
p-value: 0.75Kaplan Meier
Secondary
Cardiac Power Index
Measured 48-96 hours after randomization
Time frame: up to 96 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Cardiac Power Index | 0.61 W/m^2 |
| Therapeutic Hypothermia | Cardiac Power Index | 0.53 W/m^2 |
p-value: 0.029Mixed Models Analysis
Secondary
Changes in Cardiac Index
Difference between groups in cardiac index and output
Time frame: up to 96 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Changes in Cardiac Index | 2.6 Liter/minute/m^2 |
| Therapeutic Hypothermia | Changes in Cardiac Index | 3.6 Liter/minute/m^2 |
p-value: 0.029Mixed Models Analysis
Secondary
Changes in Systemic Vascular Resistance (SVR)
Mean SVR in population
Time frame: up to 96 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Changes in Systemic Vascular Resistance (SVR) | 965 mm Hg*min/mL |
| Therapeutic Hypothermia | Changes in Systemic Vascular Resistance (SVR) | 702 mm Hg*min/mL |
p-value: 0.091Mixed Models Analysis
Secondary
Cumulative Dobutamine Dose
Cumulative dose of weight adjusted dobutamine dobutamine
Time frame: 96 hours
Population: All trial participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Cumulative Dobutamine Dose | 0 mg/kg |
| Therapeutic Hypothermia | Cumulative Dobutamine Dose | 0 mg/kg |
p-value: 0.43t-test, 2 sided
Secondary
Cumulative Dopamine Dose
Cumulative weight adjusted dopamine dose
Time frame: 96 hours
Population: All patients in study were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Cumulative Dopamine Dose | 0 mg/kg |
| Therapeutic Hypothermia | Cumulative Dopamine Dose | 7.27 mg/kg |
p-value: 0.052t-test, 2 sided
Secondary
Cumulative Milrinone Dose
cumulative weight adjusted dosing of milrinone
Time frame: up to 96 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Cumulative Milrinone Dose | 0.28 mg/kg |
| Therapeutic Hypothermia | Cumulative Milrinone Dose | 0.36 mg/kg |
p-value: 0.7t-test, 2 sided
Secondary
Left Ventricular Ejection Fraction
percent ejection fraction on echocardiogram at 18-24 hours after randomization
Time frame: up to 18-24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Left Ventricular Ejection Fraction | 40.1 percent |
| Therapeutic Hypothermia | Left Ventricular Ejection Fraction | 28.1 percent |
p-value: 0.516Fisher Exact