Effect of the Addition of Adenosine on Myocardial Protection During Cardiopulmonary Bypass

NCT07426237 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 7.975.821
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether the addition of adenosine to standard cardioplegia improves myocardial protection in adult patients undergoing on-pump cardiac surgery. The study population includes adult patients of both sexes undergoing elective cardiac procedures requiring cardiopulmonary bypass and cardioplegic arrest. The main questions this trial aims to answer are: Does the addition of adenosine to cardioplegia affect myocardial protection as assessed by transesophageal echocardiography (TEE)? What is the effect of adenosine on biochemical markers of myocardial injury, such as postoperative high-sensitivity troponin levels? What is the effect of adenosine on perioperative hemodynamic support requirements, as quantified by the Vasoactive-Inotropic Score (VIS)? Researchers will compare patients receiving adenosine-supplemented cardioplegia with those receiving standard cardioplegia (placebo) to assess differences in echocardiographic indicators of myocardial protection, biomarker release, and need for vasoactive/inotropic support. Participants will: Receive either adenosine-supplemented cardioplegia (adenosine 1.2 mmol/L; 24 mg) or placebo according to randomization. Undergo standard perioperative monitoring during cardiac surgery. Undergo intraoperative transesophageal echocardiography (TEE) to evaluate myocardial protection by comparing pre- and post-cardiopulmonary bypass (CPB) measurements. Have postoperative laboratory testing for high-sensitivity troponin at baseline, 2h, 12h, and 24h after clamp release. Have hemodynamic support requirements recorded and VIS calculated at the end of surgery and at 12h and 24h postoperatively. Be followed for perioperative clinical outcomes including arrhythmias, need for cardioversion or mechanical circulatory support, ICU/hospital length of stay, myocardial infarction, and mortality.

Conditions

Myocardial Protection

Keywords

myocardial protection; cardioplegia; del Nido

Outcome Measures

Primary Outcomes (3)

• High-sensitivity troponin

  baseline (upon entry to the operating room) and at 2, 12, and 24 hours after aortic cross-clamp release

• Vasoactive-Inotropic Score (VIS)

  The VIS will be calculated based on the administration of vasoactive drugs using the formula described by Gaies: VIS = (dopamine µg/kg/min) + (dobutamine µg/kg/min) + (epinephrine µg/kg/min × 100) + (norepinephrine µg/kg/min × 100) + (milrinone µg/kg/min × 10) + (vasopressin units/kg/min × 10,000).

  Immediately after completion of surgery and at 12 and 24 hours after aortic cross-clamp release

• TEE assessment of myocardial protection

  by transesophageal echocardiography (TEE)

  The first measurement will be done at the day of the surgery in the operating room befere skin incision and the second one will be done whitin 1 hour after separation from cardiopulmonary bypass

Secondary Outcomes (14)

• Arrhythmias requiring cardioversion or defibrillation

  Perioperative

• Need for temporary pacing

  Periprocedural

• New-onset atrial fibrillation

  Day 1

• Use of mechanical circulatory support

  Perioperative period (during hospitalization after surgery)

• Mortality

  Perioperative period (during hospitalization after surgery)

Study Arms (2)

Adenosine

ACTIVE COMPARATOR

Drug: Adenoseine

Sterile Distilled Water

PLACEBO COMPARATOR

Drug: Placebo (sterile distilled water)

Interventions

Adenoseine DRUG

Participants randomized to the adenosine group will receive a single bolus of adenosine 1.2 mmol/L (24 mg) administered directly into the aortic root immediately after aortic cross-clamping and immediately before infusion of standard del Nido cardioplegia. The solution will be prepared by the perfusionist under sterile conditions.

Adenosine

Placebo (sterile distilled water) DRUG

Participants randomized to the placebo group will receive a single bolus of sterile distilled water, matched in volume and appearance to the adenosine solution, administered into the aortic root immediately after aortic cross-clamping and immediately prior to infusion of standard del Nido cardioplegia. The solution will be prepared by the perfusionist under sterile conditions to ensure identical volume and appearance to the placebo solution. Perioperative and postoperative management will be identical to the intervention group.

Sterile Distilled Water

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients aged 18 years or older undergoing elective isolated valve replacement or coronary artery bypass grafting with cardiopulmonary bypass at Hospital Nossa Senhora da Conceição, Porto Alegre

You may not qualify if:

• Previous cardiac surgery;
• Chronic kidney disease (serum creatinine greater than 2.0 mg/dL);
• Severe psychiatric illness;
• Urgent or emergency surgery;
• Multiple cardiac procedures.

Sponsors & Collaborators

• Hospital Nossa Senhora da Conceicao: lead

Study Sites (1)

Hospital Nossa Senhora da Conceição

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Related Publications (14)

• Allen BS. Myocardial protection: a forgotten modality. Eur J Cardiothorac Surg. 2020 Feb 1;57(2):263-270. doi: 10.1093/ejcts/ezz215.

  PMID: 31364690 RESULT

• Singh A, Huang X, Dai L, Wyler D, Alfirevic A, Blackstone EH, Pettersson GB, Duncan AE. Right ventricular function is reduced during cardiac surgery independent of procedural characteristics, reoperative status, or pericardiotomy. J Thorac Cardiovasc Surg. 2020 Apr;159(4):1430-1438.e4. doi: 10.1016/j.jtcvs.2019.04.035. Epub 2019 Apr 26.

  PMID: 31133354 RESULT

• Lira KB, Delvaux RS, Spadini FA, Hauschild LH, Ceron RO, Anschau F, Kopittke L, Rode J, Rey RAW, Wittke EI, Rombaldi AR, Cambruzzi E, Lopes ERC, Almeida AS. Myocardial protection: comparing histological effects of single-dose cardioplegic solutions-study protocol for a secondary analysis of the CARDIOPLEGIA trial. J Thorac Dis. 2024 Feb 29;16(2):1480-1487. doi: 10.21037/jtd-23-1442. Epub 2024 Feb 20.

  PMID: 38505015 RESULT

• Almeida AS, Ceron RO, Anschau F, Kopittke L, Lira KB, Delvaux RS, Rode J, Rey RAW, Wittke EI, Rombaldi AR. Comparison between Custodiol, del Nido and modified del Nido in the myocardial protection - Cardioplegia Trial: a study protocol for a randomised, double-blind clinical trial. BMJ Open. 2021 Sep 6;11(9):e047942. doi: 10.1136/bmjopen-2020-047942.

  PMID: 34489276 RESULT

• Ammar A, Mahmoud K, Elkersh A, Kasemy Z. A Randomized Controlled Trial of Intra-Aortic Adenosine Infusion Before Release of the Aortic Cross-Clamp During Coronary Artery Bypass Surgery. J Cardiothorac Vasc Anesth. 2018 Dec;32(6):2520-2527. doi: 10.1053/j.jvca.2017.10.041. Epub 2017 Dec 8.

  PMID: 29225152 RESULT

• Abdelwahab AA, Sabry M, Elshora HA, Arafat AA. Effect of Fast Cardioplegic Arrest Induced by Adenosine on Cardiac Troponin Levels After Heart Valve Surgery. Heart Lung Circ. 2019 Nov;28(11):1714-1719. doi: 10.1016/j.hlc.2018.08.017. Epub 2018 Sep 12.

  PMID: 30253969 RESULT

• 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.

  PMID: 22964356 RESULT

• 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.

  PMID: 10235522 RESULT

• Wei M, Kuukasjarvi P, Laurikka J, Honkonen EL, Kaukinen S, Laine S, Tarkka M. Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting. Chest. 2001 Sep;120(3):860-5. doi: 10.1378/chest.120.3.860.

  PMID: 11555521 RESULT

• Jakobsen O, Muller S, Aarsaether E, Steensrud T, Sorlie DG. Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection. Eur J Cardiothorac Surg. 2007 Sep;32(3):493-500. doi: 10.1016/j.ejcts.2007.05.020. Epub 2007 Jul 5.

  PMID: 17613242 RESULT

• Francica A, Tonelli F, Rossetti C, Tropea I, Luciani GB, Faggian G, Dobson GP, Onorati F. Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery. J Clin Med. 2021 Sep 29;10(19):4485. doi: 10.3390/jcm10194485.

  PMID: 34640503 RESULT

• Vinten-Johansen J, Zhao ZQ, Corvera JS, Morris CD, Budde JM, Thourani VH, Guyton RA. Adenosine in myocardial protection in on-pump and off-pump cardiac surgery. Ann Thorac Surg. 2003 Feb;75(2):S691-9. doi: 10.1016/s0003-4975(02)04694-5.

  PMID: 12607714 RESULT

• Jovanovic A, Lopez JR, Alekseev AE, Shen WK, Terzic A. Adenosine prevents K+-induced Ca2+ loading: insight into cardioprotection during cardioplegia. Ann Thorac Surg. 1998 Feb;65(2):586-91. doi: 10.1016/s0003-4975(97)01240-x.

  PMID: 9485282 RESULT

• Dobson GP, Letson HL. Adenosine, lidocaine, and Mg2+ (ALM): From cardiac surgery to combat casualty care--Teaching old drugs new tricks. J Trauma Acute Care Surg. 2016 Jan;80(1):135-45. doi: 10.1097/TA.0000000000000881.

  PMID: 26683400 RESULT

Central Study Contacts

Felipe Abatti Spadini, MD, MSc

CONTACT

+5554981181291; felipespadini@gmail.com

Andre Schimdt, PhD

CONTACT

+555133572000; apschmidt@hcpa.edu.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: February 23, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)