Leukocytes and Cardiovascular Perioperative Events-2

Elective Non-cardiac Surgery Clinical Trial

— LeukoCAPE-2  

Official title:

Assoziationen Von Leukozyten-Sub-Populationen im Blut kardiovaskulärer Risikopatienten Mit Der Inzidenz Perioperativer kardiovaskulärer Ereignisse

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03105427
• Other study ID #: LeukoCAPE02
• Status: Completed
• Phase: N/A
• First received: March 8, 2017
• Last updated: January 29, 2018
• Start date: April 10, 2017
• Est. completion date: January 5, 2018

Study information

• Verified date: January 2018
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The potential use of regulatory T cells as preoperative risk stratification tool is evaluated in order to improve clinical risk stratification and reduce perioperative morbidity and mortality.

Description:

Annually, there are more than 200 million surgeries worldwide. The POISE study revealed 5% of patients undergoing a non-cardiac surgery suffer perioperative myocardial infarcts going along with a perioperative mortality rate of about 11,6%. Possibilities to preoperatively identify patients at risk are limited and prophylactic interventions are not yet established or controversial.

Selected leukocyte subpopulations have been demonstrated to be associated with higher risk for cardiovascular events.

The aim of this study is to evaluate the potential use of regulatory T cells as preoperative risk stratification tool in order to improve clinical risk stratification and reduce perioperative morbidity and mortality. Therefore, high-risk cardiovascular patients scheduled for major non-cardiac surgery will be recruited. Blood will be drawn at predefined time points before surgery and up to three days postoperatively. Leukocytes will be analyzed by flow cytometry. During 30 day follow up adverse cardiovascular events will be recorded. ECGs will be recorded preoperatively and on post-OP day 3. High-sensitive cardiac Troponin T will be measured prior to the operation and on post-OP day one to three. The patient chart will be screened for cardiovascular events up to day 30. A telephone interview will be performed to detect cardiovascular events after discharge until post-OP day 30.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: January 5, 2018
• Est. primary completion date: January 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older

• Coronary heart disease

• Non-cardiac surgery

• Inpatient treatment

• Informed consent

Exclusion Criteria:

• 17 years of age or younger

• Known pregnancy or breastfeeding

• Missing informed consent

• Ambulatory or day-case surgery

• Emergency surgery

• Acute or chronic leukemia

• Current aplasia or leukopenia

• Current GM-CSF treatment

• Carotid artery surgery

• History of splenectomy

• Current intravenous or oral Cortisone treatment

• History of organ transplantation

• Current immunosuppressive medication

• Chemotherapy completed less than 14 days ago

• Entity which is part of the composite endpoint diagnosed within past 28 days

Related Conditions & MeSH terms

• Elective Non-cardiac Surgery

Locations

Country	Name	City	State
Germany	Department of Anaesthesiology, University Hospital Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

References & Publications (10)

Berg KE, Ljungcrantz I, Andersson L, Bryngelsson C, Hedblad B, Fredrikson GN, Nilsson J, Björkbacka H. Elevated CD14++CD16- monocytes predict cardiovascular events. Circ Cardiovasc Genet. 2012 Feb 1;5(1):122-31. doi: 10.1161/CIRCGENETICS.111.960385. Epub 2012 Jan 11. — View Citation

Devereaux PJ, Sessler DI. Cardiac Complications in Patients Undergoing Major Noncardiac Surgery. N Engl J Med. 2015 Dec 3;373(23):2258-69. doi: 10.1056/NEJMra1502824. Review. — View Citation

Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011 Apr 19;154(8):523-8. doi: 10.7326/0003-4819-154-8-201104190-00003. — View Citation

Engelbertsen D, Andersson L, Ljungcrantz I, Wigren M, Hedblad B, Nilsson J, Björkbacka H. T-helper 2 immunity is associated with reduced risk of myocardial infarction and stroke. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):637-44. doi: 10.1161/ATVBAHA.112.300871. Epub 2013 Jan 10. — View Citation

Gillmann HJ, Meinders A, Grohennig A, Larmann J, Bünte C, Calmer S, Sahlmann B, Rustum S, Aper T, Lichtinghagen R, Koch A, Teebken OE, Theilmeier G. Perioperative levels and changes of high-sensitivity troponin T are associated with cardiovascular events in vascular surgery patients. Crit Care Med. 2014 Jun;42(6):1498-506. doi: 10.1097/CCM.0000000000000249. — View Citation

Kotfis K, Biernawska J, Zegan-Baranska M, Zukowski M. Peripheral Blood Lymphocyte Subsets (CD4+, CD8+ T Cells, NK Cells) in Patients with Cardiovascular and Neurological Complications after Carotid Endarterectomy. Int J Mol Sci. 2015 May 4;16(5):10077-94. doi: 10.3390/ijms160510077. — View Citation

Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P, Große-Dunker G, Heisel I, Hornof F, Jeken J, Rebling NM, Ulrich C, Scheller B, Böhm M, Fliser D, Heine GH. CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol. 2012 Oct 16;60(16):1512-20. doi: 10.1016/j.jacc.2012.07.019. Epub 2012 Sep 19. — View Citation

Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D, Ulrich C, Fliser D, Heine GH. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J. 2011 Jan;32(1):84-92. doi: 10.1093/eurheartj/ehq371. Epub 2010 Oct 12. — View Citation

Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AA. Size and distribution of the global volume of surgery in 2012. Bull World Health Organ. 2016 Mar 1;94(3):201-209F. doi: 10.2471/BLT.15.159293. — View Citation

Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008 Jul 12;372(9633):139-44. doi: 10.1016/S0140-6736(08)60878-8. Epub 2008 Jun 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiovascular Events	Number of participants with Cardiovascular Events defined as occurrence of Cardiac Death and/or Myocardial Ischemia and/or Myocardial Infarction and/or Myocardial Injury After Non-cardiac Surgery (MINS) and/or Embolic Stroke and/or Thrombotic Stroke recorded until postoperative day 30. Definitions according to European Perioperative Clinical Outcome-(EPCO) definitions detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Secondary	Peripheral vascular occlusion	Diagnosed by a radiologist based on the results of duplex ultrasonography, angiography or CT-angiography.	30 days postoperative
Secondary	New onset atrial fibrillation	Number of participants with new electrocardiographic detection of atrial fibrillation in postoperative ECG and/or documented in patient charts	30 days postoperative
Secondary	Acute kidney injury	Number of participants with acute kidney injury according to KDIGO guidelines	30 days postoperative
Secondary	Congestive heart failure	Number of participants with congestive heart failure according to European Perioperative Clinical Outcome (EPCO) definitions	30 days postoperative
Secondary	Cardiac death	Number of participants with cardiac Death defined as death because of new myocardial infarction or ischemia, or atrial or ventricular arrhythmias, or cardiogenic pulmonary edema, or pulmonary embolism detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Secondary	Myocardial Ischemia	Number of participants with myocardial ischemia defined as new electrocardiographic detection of myocardial ischemia in ECG and/or documented in patient charts which will be screened up to 30 postoperative days and/or detected during telephone interview after 30 postoperative days	30 days postoperative
Secondary	Myocardial Infarction	Number of participants with Myocardial Infarction defined as an increase in serum cardiac biomarker values in combination with symptoms of ischemia or new/presumed new significant ST segment or T wave ECG changes or new left bundle branch block or development of pathological Q waves on ECG. Definition according to European Perioperative Clinical Outcome-(EPCO) definitions detected at postoperative visits, postoperative blood analyses, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Secondary	Myocardial Injury after Non-cardiac Surgery (MINS)	Number of participants with MINS defined as raise in postoperative hs-cTNT (high sensitivity cardiac troponin T) jugded due to myocardial ischemia detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Secondary	Stroke	Number of participants with embolic or thrombotic stroke defined cerebral event with persistent residual motor, sensory or cognitive dysfunction detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative