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Adenosine as an Adjunct to Blood Cardioplegia

Primary Purpose

Pathological Processes, Cardiomyopathies

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Adenosine
Sponsored by
Amphia Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pathological Processes focused on measuring Cardioplegia, Cardiac Surgery, Adenosine, Therapeutic Uses, Intermittent warm blood cardioplegia, Minimally Invasive Surgery, minimally invasive mitral valve plasty (mini-MPL), minimally invasive mitral valve replacement (mini-MVR)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Amphia HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

standard cardioplegia

adenosine enriched cardioplegia

Arm Description

Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 500 ml normal saline (0.9% NaCl) infusion bag. Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives standard intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: n/a

Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 1000 mg = 500 ml adenosine infusion bag (2 mg/ml). Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives adenosine enriched, intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: Drug: Adenosine

Outcomes

Primary Outcome Measures

6-hour cardiac Troponin T (cTnT) release
The primary end point is 6-hour cTnT release

Secondary Outcome Measures

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).
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
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.
Vasoconstrictor usage
Vasoconstrictor usage yes/no
Incidence of new onset Atrial fibrillation (AF)
Incidence of new onset AF
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)
Mean arterial pressure (MAP)
Haemodynamic monitoring
postoperative left ventricular ejection fraction (LVEF)
3-D transesophageal echocardiography (TEE) postoperative left ventricular ejection fraction (LVEF) after skin closure
Wall Motion Score Index (WMSI)
3-D transesophageal echocardiography (TEE) Wall Motion Score Index (WMSI) after skin closure
Heart rate (HR)
Haemodynamic monitoring. Heart rate will be measured in beats per minute (bpm).
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)
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)

Full Information

First Posted
February 3, 2016
Last Updated
April 19, 2017
Sponsor
Amphia Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02681913
Brief Title
Adenosine as an Adjunct to Blood Cardioplegia
Official Title
The Effect of Adenosine on Myocardial Protection in Intermittent Warm Blood Cardioplegia: A Randomized Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amphia Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pathological Processes, Cardiomyopathies
Keywords
Cardioplegia, Cardiac Surgery, Adenosine, Therapeutic Uses, Intermittent warm blood cardioplegia, Minimally Invasive Surgery, minimally invasive mitral valve plasty (mini-MPL), minimally invasive mitral valve replacement (mini-MVR)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard cardioplegia
Arm Type
No Intervention
Arm Description
Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 500 ml normal saline (0.9% NaCl) infusion bag. Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives standard intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: n/a
Arm Title
adenosine enriched cardioplegia
Arm Type
Experimental
Arm Description
Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 1000 mg = 500 ml adenosine infusion bag (2 mg/ml). Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives adenosine enriched, intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: Drug: Adenosine
Intervention Type
Drug
Intervention Name(s)
Adenosine
Other Intervention Name(s)
Adenocor
Intervention Description
This group receives intermittent warm blood cardioplegia enriched with adenosine
Primary Outcome Measure Information:
Title
6-hour cardiac Troponin T (cTnT) release
Description
The primary end point is 6-hour cTnT release
Time Frame
6 hours post-operative
Secondary Outcome Measure Information:
Title
18-hour cardiac Troponin T (cTnT) area under the curve (AUC) release
Description
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).
Time Frame
cardiac Troponin T (cTnT) AUC will be assessed at different time points, the latest up to 18 hours after ICU arrival
Title
Incidence of myocardial injury on 12-lead ECG
Description
Incidence of myocardial injury on 12-lead ECG New-onset Left bundle branch block (LBBB) New-onset Q wave
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Vasoactive-inotropic score
Description
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.
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Vasoconstrictor usage
Description
Vasoconstrictor usage yes/no
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Incidence of new onset Atrial fibrillation (AF)
Description
Incidence of new onset AF
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Routine blood samples
Description
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)
Time Frame
Routine blood samples will be assessed at different time points, the latest up to 6 hours after ICU arrival
Title
Mean arterial pressure (MAP)
Description
Haemodynamic monitoring
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
postoperative left ventricular ejection fraction (LVEF)
Description
3-D transesophageal echocardiography (TEE) postoperative left ventricular ejection fraction (LVEF) after skin closure
Time Frame
postoperative after skin closure, an expected average of 3 hours after starting surgery
Title
Wall Motion Score Index (WMSI)
Description
3-D transesophageal echocardiography (TEE) Wall Motion Score Index (WMSI) after skin closure
Time Frame
postoperative after skin closure, an expected average of 3 hours after starting surgery
Title
Heart rate (HR)
Description
Haemodynamic monitoring. Heart rate will be measured in beats per minute (bpm).
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Cardiac index (CI)
Description
Cardiac index (CI) is a haemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA)
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days
Title
Systemic vascular resistance index (SVRI)
Description
SVRI = 80 x (MAP - RAP)/CI MAP = Mean Arterial Pressure (mmHg) RAP = Right Arterial Pressure (mmHg) CI = Cardiac Index (L/min/m2)
Time Frame
participants will be followed for the duration of ICU stay, an expected average of 2 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jeffrey Engelhart, PharmD
Phone
0031765954391
Email
JEngelhart@amphia.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Thierry Scohy, MD
Phone
003176595570
Email
TScohy@amphia.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Engelhart, PharmD
Organizational Affiliation
Amphia Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amphia Hospital
City
Breda
State/Province
Noord-Brabant
ZIP/Postal Code
4818CK
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeffrey Engelhart, PharmD
Phone
0031765954391
Email
jengelhart@amphia.nl
First Name & Middle Initial & Last Name & Degree
Thierry Scohy, MD
Phone
0031765955570
Email
tscohy@amphia.nl

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22108937
Citation
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.
Results Reference
background
PubMed Identifier
9852907
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.
Results Reference
background
PubMed Identifier
10585118
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. doi: 10.1016/s0003-4975(99)01026-7.
Results Reference
background
PubMed Identifier
10698387
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. doi: 10.1016/s1053-0770(00)90050-8.
Results Reference
background
PubMed Identifier
10235522
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. doi: 10.1097/00000658-199905000-00006.
Results Reference
background
PubMed Identifier
22795715
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.
Results Reference
background
PubMed Identifier
22964356
Citation
Jakobsen O, Naesheim T, Aas KN, Sorlie 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.
Results Reference
background
PubMed Identifier
19683936
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.
Results Reference
background

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Adenosine as an Adjunct to Blood Cardioplegia

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