Clinical trial NCT02633358: Anti-inflammatory Effect of Therapeutic Hypothermia in Out-hospital Cardiac Arrest Patients With Cardiogenic Shock
Official title: Anti-inflammatory Effect of Therapeutic Hypothermia in Out-hospital Cardiac Arrest Patients With Cardiogenic Shock Via Interleukin-6 Trans-signaling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Arrest
Keywords: Acute myocardial infarction, cardiogenic shock
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2015-12-17
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival Rate - Number of Participants Alive
timeFrame: 90 days after enrollment
Secondary outcomes:
measure: Neurologic Outcome - Number of Participants
timeFrame: 90 days after enrollment
Other outcomes:
measure: Interleukin-6 - the Plasma Level of Participants
timeFrame: between 6 and 24 hours after enrollment.
measure: Interleukin-6/Soluble Interleukin-6 Receptor Complex - the Plasma Level of Participants
timeFrame: between 6 and 24 hours after enrollment
measure: Soluble Interleukin-6 Receptor - the Plasma Level of Participants
timeFrame: between 6 and 24 hours after enrollment
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: Chnia Medical University Hospital
name: Da-Long Chen, Master
role: STUDY_DIRECTOR
References:
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citation: Forkmann M, Kolschmann S, Holzhauser L, Ibrahim K, Guenther M, Christoph M, Fuhrmann JT, Boscheri A, Schmeibetaer A, Strasser RH, Wunderlich C. Target temperature management of 33 degrees C exerts beneficial haemodynamic effects after out-of-hospital cardiac arrest. Acta Cardiol. 2015 Aug;70(4):451-9. doi: 10.1080/ac.70.4.3096893.
citation: Nobile L, Lamanna I, Fontana V, Donadello K, Dell'anna AM, Creteur J, Vincent JL, Pappalardo F, Taccone FS. Greater temperature variability is not associated with a worse neurological outcome after cardiac arrest. Resuscitation. 2015 Nov;96:268-74. doi: 10.1016/j.resuscitation.2015.09.004. Epub 2015 Sep 16.
citation: Bro-Jeppesen J, Kjaergaard J, Wanscher M, Nielsen N, Friberg H, Bjerre M, Hassager C. Systemic Inflammatory Response and Potential Prognostic Implications After Out-of-Hospital Cardiac Arrest: A Substudy of the Target Temperature Management Trial. Crit Care Med. 2015 Jun;43(6):1223-32. doi: 10.1097/CCM.0000000000000937.
citation: Dankiewicz J, Nielsen N, Annborn M, Cronberg T, Erlinge D, Gasche Y, Hassager C, Kjaergaard J, Pellis T, Friberg H. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography: a post hoc analysis from the TTM trial. Intensive Care Med. 2015 May;41(5):856-64. doi: 10.1007/s00134-015-3735-z. Epub 2015 Mar 24.