Adenosine as an Adjunct to Blood Cardioplegia

Cardiomyopathies Clinical Trial

Official title:

The Effect of Adenosine on Myocardial Protection in Intermittent Warm Blood Cardioplegia: A Randomized Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02681913
• Other study ID #: 1437
• Secondary ID: 2015-001923-22
• Status: Recruiting
• Phase: Phase 2
• First received: February 3, 2016
• Last updated: April 19, 2017
• Start date: February 2016
• Est. completion date: December 2018

Study information

• Verified date: April 2017
• Source: Amphia Hospital
• Contact: Jeffrey Engelhart, PharmD
• Phone: 0031765954391
• Email: JEngelhart[@]amphia.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Myocardial protection is a major issue in cardiac surgery, since inadequate protection increases the risk of postoperative cardiac dysfunction. The main principle of myocardial protection in cardiac surgery is to preserve myocardial function by preventing ischemia with blood cardioplegia . Previous studies have shown that adenosine as an adjunct to blood cardioplegia can be safely used in cardiac surgery. In the Amphia Hospital, adenosine is already used as standard care as an initial cardioplegic bolus in minimally invasive port access operations. Whether, adenosine as an adjunct to intermittent warm blood cardioplegia, has an added value remains unclear. Therefore the investigators would like to investigate the effect of the addition of adenosine to standard intermittent warm blood cardioplegia in patients scheduled for minimally invasive, port access operations (mitral valve surgery).

Half of the participants will receive standard intermittent warm blood cardioplegia, while the other half will receive intermittent warm blood cardioplegia enriched with adenosine.

Description:

Myocardial protection is a major issue in cardiac surgery, since inadequate protection increases the risk of postoperative cardiac dysfunction. The main principle of myocardial protection in cardiac surgery is to preserve myocardial function by preventing ischemia with blood cardioplegia . Previous studies have shown that adenosine as an adjunct to blood cardioplegia can be safely used in cardiac surgery. In the Amphia Hospital, adenosine is already used as standard care as an initial cardioplegic bolus in minimally invasive port access operations. Whether, adenosine as an adjunct to intermittent warm blood cardioplegia, has an added value remains unclear. Therefore the investigators would like to investigate whether the addition of adenosine to standard intermittent warm blood cardioplegia reduces the 6-hours post-operative cardiac troponin T (cTnT) in patients scheduled for minimally invasive, port access operations (mitral valve surgery).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Elective cardiac surgical patients

• minimally invasive, port access surgery (mitral valve surgery)

Exclusion Criteria:

• All non-minimally invasive, port access surgery

• Theophylline or dipyridamole use up to 24 hours prior to surgery

• Products that contain caffeine of theobromine up to 12 hours prior to surgery (coffee, chocolate, energizing drinks (e.g. Red Bull), tea, soda (coke), etc)

Related Conditions & MeSH terms

• Cardiomyopathies
• Pathologic Processes
• Pathological Processes

Intervention

Drug:
• Adenosine
This group receives intermittent warm blood cardioplegia enriched with adenosine

Locations

Country	Name	City	State
Netherlands	Amphia Hospital	Breda	Noord-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Amphia Hospital

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

Ahlsson A, Sobrosa C, Kaijser L, Jansson E, Bomfim V. Adenosine in cold blood cardioplegia--a placebo-controlled study. Interact Cardiovasc Thorac Surg. 2012 Jan;14(1):48-55. doi: 10.1093/icvts/ivr027. Epub 2011 Nov 15. — View Citation

Chauhan S, Wasir HS, Bhan A, Rao BH, Saxena N, Venugopal P. Adenosine for cardioplegic induction: a comparison with St Thomas solution. J Cardiothorac Vasc Anesth. 2000 Feb;14(1):21-4. — View Citation

Cohen G, Borger MA, Weisel RD, Rao V. Intraoperative myocardial protection: current trends and future perspectives. Ann Thorac Surg. 1999 Nov;68(5):1995-2001. Review. — View Citation

Cohen G, Feder-Elituv R, Iazetta J, Bunting P, Mallidi H, Bozinovski J, Deemar C, Christakis GT, Cohen EA, Wong BI, McLean RD, Myers M, Morgan CD, Mazer CD, Smith TS, Goldman BS, Naylor CD, Fremes SE. Phase 2 studies of adenosine cardioplegia. Circulation. 1998 Nov 10;98(19 Suppl):II225-33. — View Citation

Jakobsen Ø, Næsheim T, Aas KN, Sørlie D, Steensrud T. Adenosine instead of supranormal potassium in cardioplegia: it is safe, efficient, and reduces the incidence of postoperative atrial fibrillation. A randomized clinical trial. J Thorac Cardiovasc Surg. 2013 Mar;145(3):812-8. doi: 10.1016/j.jtcvs.2012.07.058. Epub 2012 Sep 7. — View Citation

Liu R, Xing J, Miao N, Li W, Liu W, Lai YQ, Luo Y, Ji B. The myocardial protective effect of adenosine as an adjunct to intermittent blood cardioplegia during open heart surgery. Eur J Cardiothorac Surg. 2009 Dec;36(6):1018-23. doi: 10.1016/j.ejcts.2009.06.033. Epub 2009 Aug 15. — View Citation

Mentzer RM Jr, Birjiniuk V, Khuri S, Lowe JE, Rahko PS, Weisel RD, Wellons HA, Barker ML, Lasley RD. Adenosine myocardial protection: preliminary results of a phase II clinical trial. Ann Surg. 1999 May;229(5):643-9; discussion 649-50. — View Citation

Onorati F, Santini F, Dandale R, Ucci G, Pechlivanidis K, Menon T, Chiominto B, Mazzucco A, Faggian G. "Polarizing" microplegia improves cardiac cycle efficiency after CABG for unstable angina. Int J Cardiol. 2013 Sep 10;167(6):2739-46. doi: 10.1016/j.ijcard.2012.06.099. Epub 2012 Jul 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-hour cardiac Troponin T (cTnT) release	The primary end point is 6-hour cTnT release	6 hours post-operative
Secondary	18-hour cardiac Troponin T (cTnT) area under the curve (AUC) release	18-hour postoperative AUC release of cardiac troponin T Routine blood samples pre-operatively from peripheral blood (T0); post-operatively, from peripheral blood, at arrival at ICU (T1) and 6 hours after arrival at ICU (T2), and 18 hours after arrival at ICU (T3).	cardiac Troponin T (cTnT) AUC will be assessed at different time points, the latest up to 18 hours after ICU arrival
Secondary	Incidence of myocardial injury on 12-lead ECG	Incidence of myocardial injury on 12-lead ECG; New-onset Left bundle branch block (LBBB); New-onset Q wave	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Vasoactive-inotropic score	The hourly doses of the following inotropic and vasoactive medications are recorded for the first 18 h after post-operative admission to the ICU: dopamine, dobutamine, epinephrine, norepinephrine, milrinone and vasopressin.	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Vasoconstrictor usage	Vasoconstrictor usage yes/no	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Incidence of new onset Atrial fibrillation (AF)	Incidence of new onset AF	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Routine blood samples	The amount of creatine kinase MB (CK-MB) and Creatinine at different time intervals. preoperatively from peripheral blood (T0); post-operatively, from peripheral blood, at arrival at ICU (T1) and 6 hours after arrival at ICU (T2)	Routine blood samples will be assessed at different time points, the latest up to 6 hours after ICU arrival
Secondary	Mean arterial pressure (MAP)	Haemodynamic monitoring	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	postoperative left ventricular ejection fraction (LVEF)	3-D transesophageal echocardiography (TEE) postoperative left ventricular ejection fraction (LVEF) after skin closure	postoperative after skin closure, an expected average of 3 hours after starting surgery
Secondary	Wall Motion Score Index (WMSI)	3-D transesophageal echocardiography (TEE) Wall Motion Score Index (WMSI) after skin closure	postoperative after skin closure, an expected average of 3 hours after starting surgery
Secondary	Heart rate (HR)	Haemodynamic monitoring. Heart rate will be measured in beats per minute (bpm).	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Cardiac index (CI)	Cardiac index (CI) is a haemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA)	participants will be followed for the duration of ICU stay, an expected average of 2 days
Secondary	Systemic vascular resistance index (SVRI)	SVRI = 80 x (MAP - RAP)/CI MAP = Mean Arterial Pressure (mmHg) RAP = Right Arterial Pressure (mmHg) CI = Cardiac Index (L/min/m2)	participants will be followed for the duration of ICU stay, an expected average of 2 days