Anti-inflammatory Effect of Therapeutic Hypothermia in Out-hospital Cardiac Arrest Patients With Cardiogenic Shock

Cardiac Arrest Clinical Trial

Official title:

Anti-inflammatory Effect of Therapeutic Hypothermia in Out-hospital Cardiac Arrest Patients With Cardiogenic Shock Via Interleukin-6 Trans-signaling

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02633358
• Other study ID #: CMUH104-REC3-058
• Status: Completed
• Phase: N/A
• Start date: November 1, 2015
• Est. completion date: August 18, 2018

Study information

• Verified date: July 2019
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: August 18, 2018
• Est. primary completion date: August 18, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Hypothermia
• Shock, Cardiogenic

Intervention

Device:
• Therapeutic hypothermia group
Therapeutic hypothermia

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (6)

Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Åneman A, Horn J, Devaux Y, Erlinge D, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Nielsen N, Hassager C; TTM-Trial Investigators. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C. Resuscitation. 2016 Jan;98:1-8. doi: 10.1016/j.resuscitation.2015.10.009. Epub 2015 Oct 23. — View 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. — View 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. Erratum in: Intensive Care Med. 2015 Jun;41(6):1177. — View Citation

Forkmann M, Kolschmann S, Holzhauser L, Ibrahim K, Guenther M, Christoph M, Fuhrmann JT, Boscheri A, Schmeißer 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. — View 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. — View Citation

Schmitt KR, Tong G, Berger F. Mechanisms of hypothermia-induced cell protection in the brain. Mol Cell Pediatr. 2014 Dec;1(1):7. doi: 10.1186/s40348-014-0007-x. Epub 2014 Dec 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Interleukin-6 - the Plasma Level of Participants	IL-6 level change	between 6 and 24 hours after enrollment.
Other	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	between 6 and 24 hours after enrollment
Other	Soluble Interleukin-6 Receptor - the Plasma Level of Participants	Check the soluble Interleukin-6 plasma level at 6 hours and 24 hours after enrollment	between 6 and 24 hours after enrollment
Primary	Survival Rate - Number of Participants Alive	Survival rate according to the number of participants alive in the 90 days after enrollment.	90 days after enrollment
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.	90 days after enrollment