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Coronary Artery Bypass SurgeryPhase 2MACBCNCT02303704

Myocardial Protection With Multiport Antegrade Cold Blood Cardioplegia

A Phase 2 study testing multiport antegrade cardioplegia and Aortic root antegrade cardioplegia in people with Coronary Artery Bypass Surgery, run by Chaudhry Pervaiz Elahi Institute of Cardiology.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In spite improvements in methods of myocardial protection, peri-operative myocardial damage is still the commonest cause of early morbidity and mortality after technically successful CABG Surgery. What is the optimum method of myocardial protection is still debatable. Read more about this study

Who is it for?
Any age
Conditions the study is for
Coronary Artery Bypass Surgery
What is being tested?
multiport antegrade cardioplegia and Aortic root antegrade cardioplegia
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
448 participants
Where
No sites listed yet
Study dates
Apr 2013to Aug 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • All patients undergoing isolated conventional CABG were included in the study

Who cannot join

  • The redo CABG surgery. Those who required 2 or less than 2 grafts. Patients who had major postoperative neurological complications like stroke. 2nd arterial graft along with LIMA. Patients who need CABG within a week of STEMI or NSTEMI. Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis

About this study

Official title: Myocardial Protection With Multiport Antegrade Cold Blood Cardioplegia and Continuous Controlled Warm Shot Through Vein Grafts During Proximal Ends Anastomosis in Conventional CABG

In spite improvements in methods of myocardial protection, peri-operative myocardial damage is still the commonest cause of early morbidity and mortality after technically successful CABG Surgery. What is the optimum method of myocardial protection is still debatable.

The investigators conducted this study to see effects of multiport antegrade cold blood cardioplegia on myocardial protection, along with continuous controlled warm blood perfusion through veins graft during proximal ends anastomosis in conventional CABG surgery in patients having multi-vessel disease.

Read the detailed description

A prospective randomized controlled study was conducted between April-2013 and June-2014, in the Department of Cardiac Surgery, Chaudary Pervaiz Elahi Institute of cardiology (CPEIC) Multan, Pakistan. The CPEIC is a tertiary cardiac care center and is presently performing over 600 coronary artery bypass surgery annually. The study was conducted in strict compliance of the rules established by the revised Helsinki convention and had approval from the ethical committee of the institute.

Patients undergoing isolated conventional CABG were included in the study except; The redo CABG, those who required 2 or less than 2 grafts, patients who had major postoperative neurological complications like stroke, 2nd arterial graft along with LIMA, patients who need CABG within a week of STEMI or NSTEMI and Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis.

The patients were randomized into two groups by using draw randomization technique. The investigators made 112 sets, each set containing four patients. The staff nurse on duty was requested to pick up the two folded papers from four containing hidden identity of the patients. The patients chosen by draw were included in the study group, others in the control group.

Group I: Patients who received multiport antegrade cardioplegia and continuous controlled warm blood perfusion through vein grafts (Study Group) and Group II: Patients who underwent routine conventional CABG with antegrade aortic root cardioplegia without warm blood perfusion (Control Group).

All operations were carried out by two consultant surgeons at the investigators institution, who are certified cardiac surgeons with sufficient experience. Patients were premedicated with oral dose of 3mg bromazepam the night before surgery. Anaesthesia was induced with intra-venous morphine (0.1mg/kg), midazolam (0.05-0.1 mg /kg), and propofol (1.0-2.5 mg/kg titrated according to the response. They were given atracuronium (1mg/kg) before endotracheal intubation. The anaesthesia was maintained with sevoflorane/isoflurane.

In all patients the standard cardiopulmonary bypass (CPB) was established with an ascending aortic arterial cannula and a two stage single venous cannula in the right atrium. The CPB circuit was primed with crystalloid Ringer's solution. Heparin was administered in a dose of 400 U/Kg. The body temperature was lowered to 30-32°C. The local cooling was achieved with ice cold saline. Cold blood cardioplegia was used in each group. The first dose of cardioplegia was 10-15 ml/kg and further doses were given as 5-7ml/kg repeated after each graft or after 20 minutes. Cold blood cardioplegia was given by using cardioplegia delivery system including heat exchanger in both groups. A cardioplegia delivery cannula with a separate vent line (DLP Medtronic, Grand Rapids, MI, USA) was inserted into the ascending aorta. The pump flow rate was kept between 2.0 and 2.4 L/min/m2 to maintain a mean arterial pressure of 55 - 70 mmHg. In both groups, myocardial protection was achieved by an initial antegrade infusion of cold (4 °C) blood cardioplegic potassium solution followed by intermittent antegrade cold blood cardioplegia at the completion of each distal anastomosis via a cardioplegia delivery cannula from the aortic root. Whereas in Group I, a multiple perfusion set was used to deliver cardioplegia simultaneously in aortic root and vein grafts. After the distal anastomosis of each vein graft had been completed, the proximal ends were connected to the free branch of the multi- perfusion set. In this way, simultaneous intermittent antegrade graft cardioplegia was administered in addition to aortic root cardioplegia (named as multiport antegrade cardioplegia).

LIMA and great saphenous vein were used as conduits. LIMA was anastomosed to LAD and other coronary vessels received greater saphenous vein grafts as conduits.

Just before the removal of the aortic cross-clamp, warm blood shot (normo-kalemic) was started through multi-perfusion set attached to cardioplegia cannula in the aortic root and vein grafts in Group I. As contraction of heart started the multiport limb attached to cardioplegia cannula was off and cross clamp was removed .The warm perfusion through the vein grafts was continued at controlled pressures of about 50-70 mmHg, flow rate of 10-30ml/min/graft and temperature of 35-37 oC. Proximal anastmosis was performed in both groups using partial occluding clamp.

The necessity of inotropic support and the choice of inotropic drugs to be administered during weaning from cardiopulmonary bypass (CPB) were determined by a cardiac anaesthetist team, who were blinded and independent with respect to the study.

The CK-MB levels were determined at five points of time i.e. before operation, immediately after shifting to ICU, at 12, 24 hours and 36 hours after shifting of patient to ICU. The reagent used for determining the serum CK-MB levels was the product of Merck (Merck, France) and the designated reference value for detection of myocardial damage were >25 units/liter for CK-MB.

448 patient characteristics were prospectively entered in the investigators electronic database (CASCADE DATABASES, Lahore, Pakistan). The study specific data not included in the database were separately entered in a Microsoft Excel spreadsheet (MS Excel, version 2007, Microsoft Co USA). The statistical analysis was carried out using SPSS (SPSS version 20, SPSS Inc, Chicago, IL). The preoperative, operative and postoperative characteristics were summarized using means and standard deviation for the numeric variables. The groups were compared using Student's t-test for numeric variables and Chi-square test for categorical variables.

The significance of differences between the groups was expressed as p-value and a value of <0.05 was considered significant.

Being tested
multiport antegrade cardioplegia, Aortic root antegrade cardioplegia
Keywords
Multiperfusion set, Myocardial protection, Coronary Artery Bypass Grafting

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • multiport antegrade cardioplegiaProcedure or surgery

    Also called multiperfusion set

    Cold blood cardioplegia was used for myocardial protection and just before the removal of the aortic cross-clamp, warm blood shot (normo-kalemic) was started through multi-perfusion set attached to cardioplegia cannula in the aortic root and vein grafts.As contraction of heart started the multiport limb attached to cardioplegia cannula was off and cross clamp was removed .The warm perfusion through the vein grafts was continued at controlled pressures of about 50-70 mmHg, flow rate of 10-30ml/min/graft and temperature of 35-37 oC

  • Aortic root antegrade cardioplegiaProcedure or surgery

    only cold blood cardioplegia was used for myocardial protection without hotshot.

Study groups in NCT02303704
Study groupRoleWhat they receive
multiport antegrade cardioplegiaActive comparatorPatients who received multiport antegrade cardioplegia and continuous controlled warm blood perfusion through vein grafts.
Receives: Procedure: multiport antegrade cardioplegia
Aortic root antegrade cardioplegiaActive comparatorPatients who underwent routine conventional CABG with antegrade aortic root cardioplegia without warm blood perfusion
Receives: Procedure: Aortic root antegrade cardioplegia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Post-op CK-MB Levels

    CK-MB is a marker of Myocardial Damage.

    Measured: 36 hours after surgery.

Secondary outcomes (5)
  1. Pharmacologic Inotropic Support (Adrenaline)

    The need, dose and duration of adrenaline infusion to maintain hemodynamic stability after surgery were noted.

    Measured: Upto 1 week after sugery

  2. Pharmacological Inotropic Support (Nor-adrenaline)

    The need, dose and duration of Nor-adrenaline infusion to maintain hemodynamic stability after surgery.

    Measured: Upto 1 week after sugery

  3. Pharamacological Inotropic Support (Dobutamine)

    The Need, Dose and duration of Dobutamine to maintain hemodynamic stability after surgery.

    Measured: Upto 1 week after sugery

  4. Intra-aortic Balloon Pump Counter-pulsation (IABPC) Support

    The need of IABPC (mechanical support) before surgery or during weaning from Cardiopulmonary bypass and in ICU to assist in maintaining hemodynamics of the patient.

    Measured: 24 hours before surgery and upto 1 week of surgical procedure.

  5. Operative Mortality

    Deaths due to surgical complication during or after surgery.

    Measured: Within 30 days after surgical Procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2014 (estimated)
  2. Study startApr 2013
  3. Primary completionJun 2014
  4. Study completionAug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
448 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02303704
Sponsor's protocol ID
multanic
Acronym
MACBC
Status last verified
Feb 2021
First submitted
19 Nov 2014
Last updated
9 Feb 2021
Data monitoring committee
No

Publications

  • Mack MJ, Brown PP, Kugelmass AD, Battaglia SL, Tarkington LG, Simon AW, Culler SD, Becker ER. Current status and outcomes of coronary revascularization 1999 to 2002: 148,396 surgical and percutaneous procedures. Ann Thorac Surg. 2004 Mar;77(3):761-6; discussion 766-8. doi: 10.1016/j.athoracsur.2003.06.019.

    PubMed 14992867
  • Onorati F, De Feo M, Mastroroberto P, Cristodoro L, Pezzo F, Renzulli A, Cotrufo M. Determinants and prognosis of myocardial damage after coronary artery bypass grafting. Ann Thorac Surg. 2005 Mar;79(3):837-45. doi: 10.1016/j.athoracsur.2004.07.060.

    PubMed 15734390
  • Steuer J, Horte LG, Lindahl B, Stahle E. Impact of perioperative myocardial injury on early and long-term outcome after coronary artery bypass grafting. Eur Heart J. 2002 Aug;23(15):1219-27. doi: 10.1053/euhj.2002.3171.

    PubMed 12127924
  • Soltesz EG, Laurence RG, De Grand AM, Cohn LH, Mihaljevic T, Frangioni JV. Image-guided quantification of cardioplegia delivery during cardiac surgery. Heart Surg Forum. 2007;10(5):E381-6. doi: 10.1532/HSF98.20071099.

    PubMed 17855203
  • Sanjay OP, Srikrishna SV, Prashanth P, Kajrekar P, Vincent V. Antegrade versus antegrade with retrograde delivery of cardioplegic solution in myocardial revascularisation. A clinical study in patients with triple vessel coronary artery disease. Ann Card Anaesth. 2003 Jul;6(2):143-8.

    PubMed 17827576
  • Teoh KH, Christakis GT, Weisel RD, Fremes SE, Mickle DA, Romaschin AD, Harding RS, Ivanov J, Madonik MM, Ross IM, et al. Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia. J Thorac Cardiovasc Surg. 1986 Jun;91(6):888-95.

    PubMed 3520161
  • Onorati F, Renzulli A, De Feo M, Santarpino G, Gregorio R, Biondi A, Cerasuolo F, Cotrufo M. Does antegrade blood cardioplegia alone provide adequate myocardial protection in patients with left main stem disease? J Thorac Cardiovasc Surg. 2003 Nov;126(5):1345-51. doi: 10.1016/s0022-5223(03)00736-0.

    PubMed 14666005
  • Tian G, Xiang B, Dai G, Sun J, Lindsay WG, Deslauriers R. Simultaneous antegrade/retrograde cardioplegia protects myocardium distal to a coronary occlusion: a study in isolated pig hearts. Magn Reson Med. 2001 Oct;46(4):773-80. doi: 10.1002/mrm.1256.

    PubMed 11590654
  • Allen BS, Winkelmann JW, Hanafy H, Hartz RS, Bolling KS, Ham J, Feinstein S. Retrograde cardioplegia does not adequately perfuse the right ventricle. J Thorac Cardiovasc Surg. 1995 Jun;109(6):1116-24; discussion 1124-6. doi: 10.1016/S0022-5223(95)70195-8.

    PubMed 7776676
  • Ardehali A, Gates RN, Laks H, Drinkwater DC Jr, Rudis E, Sorensen TJ, Chang P, Aharon A. The regional capillary distribution of retrograde blood cardioplegia in explanted human hearts. J Thorac Cardiovasc Surg. 1995 May;109(5):935-9; discussion 939-40. doi: 10.1016/S0022-5223(95)70319-5.

    PubMed 7739255
  • Carrier M, Gregoire J, Khalil A, Thai P, Latour JG, Pelletier LC. Myocardial distribution of retrograde cardioplegic solution assessed by myocardial thallium 201 uptake. J Thorac Cardiovasc Surg. 1994 Dec;108(6):1115-8.

    PubMed 7983880
  • Sabzi F, Zokaei A. Factors predicting coronary sinus rupture following cannula insertion for retrograde cardioplegia. Clin Med Insights Cardiol. 2012;6:1-6. doi: 10.4137/CMC.S7861. Epub 2011 Dec 6.

    PubMed 22259260
  • Panos AL, Ali IS, Birnbaum PL, Barrozo CA, al-Nowaiser O, Salerno TA. Coronary sinus injuries during retrograde continuous normothermic blood cardioplegia. Ann Thorac Surg. 1992 Dec;54(6):1137-8. doi: 10.1016/0003-4975(92)90082-f.

    PubMed 1449299
  • Radmehr H, Soleimani A, Tatari H, Salehi M. Does combined antegrade-retrograde cardioplegia have any superiority over antegrade cardioplegia? Heart Lung Circ. 2008 Dec;17(6):475-7. doi: 10.1016/j.hlc.2008.04.009. Epub 2008 Jul 26.

    PubMed 18676202
  • Guyton RA, Thourani VH, Puskas JD, Shanewise JS, Steele MA, Palmer-Steele CL, Vinten-Johansen J. Perfusion-assisted direct coronary artery bypass: selective graft perfusion in off-pump cases. Ann Thorac Surg. 2000 Jan;69(1):171-5. doi: 10.1016/s0003-4975(99)01386-7.

    PubMed 10654508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing multiport antegrade cardioplegia and Aortic root antegrade cardioplegia in people with Coronary Artery Bypass Surgery, run by Chaudhry Pervaiz Elahi Institute of Cardiology.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post-op CK-MB Levels (time frame: 36 hours after surgery.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02303704, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.

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