Cardiac Arrest
Conditions
Keywords
Acute myocardial infarction, cardiogenic shock
Brief summary
Acute myocardial infarction complicated with cardiogenic shock trigger IL-6, the strong inflammatory response, result in multiple organ failure, even death. While therapeutic hypothermia,to expect the possibility of anti-inflammatory effect via IL-6 bi-phasic effect and IL-10 , to improve the multiple organ failure, to increase survival rate and well cerebral performance.
Detailed description
Despite emergency coronary revascularization coupled with medical stabilization, intra-aortic balloon pump have significantly improved survival in patients with cardiogenic shock complicating acute myocardial infarction, mortality still remains excessively high, being actually about 30-50%. Future research should focus on new therapeutic strategies, aimed to further decrease mortality rate of these patients or improve possible hospitalization and prognosis. Heart pumping failure result in cardiogenic shock. Increased LA filling pressure result in acute pulmonary edema, hypoxemic respiratory failure, even congestive kidney and congestive liver. Decreased stroke volume result in hypoperfusion obviously direct induce acute renal failure, disturbance consciousness and lactate accumulation, even, shock liver. Multiple organ failure is the major mortality in the patients suffered from cardiogenic shock after acute myocardial infarction. Cardiogenic shock remains the leading cause of death in patients hospitalized for myocardial infarction . Systemic inflammation , especially endovascular Interleukin-6, triggered by Tumor necrosis factor-alfa and Interleukin-1 beta result in inappropriate vasodilatation is observed in many patients with cardiogenic shock and may contribute to an excess mortality rate. In recent study, interleukin-6 represented a reliable independent early prognostic marker of 30-day mortality. Therapeutic hypothermia (34℃) increase stroke volume, reduce muscle oxygen consumption and enhance anti-inflammatory action . The mechanism of anti-inflammatory effect for therapeutic hypothermia in cardiogenic shock is still unclear, need to further study in clinical trial. Furthermore, this study will provide new strategy to increase survival rate in cardiogenic shock.
Interventions
DEVICETherapeutic hypothermia group
Therapeutic hypothermia
Sponsors
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18-100 years * Cardiogenic sock including initial lactate level \>18 mg/dL, necessary of vasopressor to keep mean artery pressure \>65mmHg after adequate fluid supply, and signs of reduced cardiac output including disturbance consciousness, cold limbs, decreased urine output, acute pulmonary congestion and so on.
Exclusion criteria
* Patient or family refuse * Metastatic cancer * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate - Number of Participants Alive | 90 days after enrollment | Survival rate according to the number of participants alive in the 90 days after enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurologic Outcome - Number of Participants | 90 days after enrollment | Neurological outcome according to Cerebral performance Category scales: scales 1-2 in favor of favorable neurological outcome; scales 3-5 in favor of poor neurological outcome including severe cerebral disability, coma or vegetative state, brain death. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Interleukin-6 - the Plasma Level of Participants | between 6 and 24 hours after enrollment. | IL-6 level change |
| Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants | between 6 and 24 hours after enrollment | Interleukin-6/soluble Interleukin-6 receptor complex plasma level hint the pro-inflammatory pathway via Interleukin-6 trans-signaling |
| Soluble Interleukin-6 Receptor - the Plasma Level of Participants | between 6 and 24 hours after enrollment | Check the soluble Interleukin-6 plasma level at 6 hours and 24 hours after enrollment |
Countries
Taiwan
Participant flow
Recruitment details
Recruitment period: 2015 Jan. to 2018 Apr. Types of location: Cardiac intensive care units, China Medical University Hospital, Taichung, Taiwan
Participants by arm
| Arm | Count |
|---|---|
| Therapeutic Hypothermia Anti-inflammatory effect of therapeutic hypothermia. The hypothesis is anti-inflammatory effect triggered by IL-6 trans-signaling
Therapeutic hypothermia: Therapeutic hypothermia | 87 |
| Non-Hypothermia Control group for non-hypothermia. Anti-inflammatory effect of therapeutic hypothermia. The hypothesis is anti-inflammatory effect triggered by IL-6 trans-signaling | 54 |
| Total | 141 |
Baseline characteristics
| Characteristic | Therapeutic Hypothermia | Non-Hypothermia | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 24 Participants | 61 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 30 Participants | 80 Participants |
| Race/Ethnicity, Customized Chinese in Taiwan | 86 participants | 54 participants | 140 participants |
| Race/Ethnicity, Customized Japanese | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Taiwan | 87 participants | 54 participants | 141 participants |
| Sex: Female, Male Female | 17 Participants | 12 Participants | 29 Participants |
| Sex: Female, Male Male | 70 Participants | 42 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 87 | 34 / 54 |
| other Total, other adverse events | 0 / 87 | 0 / 54 |
| serious Total, serious adverse events | 57 / 87 | 44 / 54 |
Outcome results
Primary
Survival Rate - Number of Participants Alive
Survival rate according to the number of participants alive in the 90 days after enrollment.
Time frame: 90 days after enrollment
Population: Randomized divided to two groups including therapeutic hypothermia group and non-hypothermia group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Therapeutic Hypothermia | Survival Rate - Number of Participants Alive | Survival | 55 Participants |
| Therapeutic Hypothermia | Survival Rate - Number of Participants Alive | Non-survival | 32 Participants |
| Non-hypothermia | Survival Rate - Number of Participants Alive | Survival | 20 Participants |
| Non-hypothermia | Survival Rate - Number of Participants Alive | Non-survival | 34 Participants |
Comparison: Therapeutic hypothermia group compare with control groupp-value: <0.00195% CI: [0.41, 0.82]Chi-squared
Secondary
Neurologic Outcome - Number of Participants
Neurological outcome according to Cerebral performance Category scales: scales 1-2 in favor of favorable neurological outcome; scales 3-5 in favor of poor neurological outcome including severe cerebral disability, coma or vegetative state, brain death.
Time frame: 90 days after enrollment
Population: Randomized divided to two groups including therapeutic hypothermia group and non-hypothermia group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Therapeutic Hypothermia | Neurologic Outcome - Number of Participants | Poor neurologic outcome | 57 Participants |
| Therapeutic Hypothermia | Neurologic Outcome - Number of Participants | Favorable neurologic outcome | 30 Participants |
| Non-hypothermia | Neurologic Outcome - Number of Participants | Poor neurologic outcome | 44 Participants |
| Non-hypothermia | Neurologic Outcome - Number of Participants | Favorable neurologic outcome | 10 Participants |
Comparison: Therapeutic hypothermia group compare with control groupp-value: 0.0495% CI: [0.66, 0.98]Chi-squared
Other Pre-specified
Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants
Interleukin-6/soluble Interleukin-6 receptor complex plasma level hint the pro-inflammatory pathway via Interleukin-6 trans-signaling
Time frame: between 6 and 24 hours after enrollment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Hypothermia | Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants | 6 hours after enrollment | 169.1 pg/mL | Standard Error 7.6 |
| Therapeutic Hypothermia | Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants | 24 hours after enrollment | 207.8 pg/mL | Standard Error 14.6 |
| Non-hypothermia | Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants | 6 hours after enrollment | 188.1 pg/mL | Standard Error 14.2 |
| Non-hypothermia | Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants | 24 hours after enrollment | 319.7 pg/mL | Standard Error 24.5 |
p-value: <0.05t-test, 2 sided
Other Pre-specified
Interleukin-6 - the Plasma Level of Participants
IL-6 level change
Time frame: between 6 and 24 hours after enrollment.
Population: Randomized divided to two groups including therapeutic hypothermia and non-hypothermia group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Hypothermia | Interleukin-6 - the Plasma Level of Participants | 6 hours after enrollment | 2064.1 pg/mL | Standard Error 178.2 |
| Therapeutic Hypothermia | Interleukin-6 - the Plasma Level of Participants | 24 hours after enrollment | 914.5 pg/mL | Standard Error 187.8 |
| Non-hypothermia | Interleukin-6 - the Plasma Level of Participants | 6 hours after enrollment | 2392.4 pg/mL | Standard Error 181.3 |
| Non-hypothermia | Interleukin-6 - the Plasma Level of Participants | 24 hours after enrollment | 5125.0 pg/mL | Standard Error 592 |
p-value: <0.05t-test, 2 sided
Other Pre-specified
Soluble Interleukin-6 Receptor - the Plasma Level of Participants
Check the soluble Interleukin-6 plasma level at 6 hours and 24 hours after enrollment
Time frame: between 6 and 24 hours after enrollment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Hypothermia | Soluble Interleukin-6 Receptor - the Plasma Level of Participants | 6 hours after enrollment | 40.6 ng/mL | Standard Error 1.6 |
| Therapeutic Hypothermia | Soluble Interleukin-6 Receptor - the Plasma Level of Participants | 24 hours after enrollment | 37.9 ng/mL | Standard Error 1.3 |
| Non-hypothermia | Soluble Interleukin-6 Receptor - the Plasma Level of Participants | 6 hours after enrollment | 37.9 ng/mL | Standard Error 1.6 |
| Non-hypothermia | Soluble Interleukin-6 Receptor - the Plasma Level of Participants | 24 hours after enrollment | 35.7 ng/mL | Standard Error 1.5 |
p-value: <0.05t-test, 2 sided