Ignite Creation Date:
2025-12-24 @ 7:07 PM
Ignite Modification Date:
2025-12-25 @ 4:41 PM
Study NCT ID:
NCT07205757
Status:
RECRUITING
Last Update Posted:
2025-11-17
First Post:
2025-09-18
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Adding Lidocaine to Custodiol Mixture
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D008012', 'term': 'Lidocaine'}, {'id': 'C039984', 'term': 'Bretschneider cardioplegic solution'}], 'ancestors': [{'id': 'D000083', 'term': 'Acetanilides'}, {'id': 'D000813', 'term': 'Anilides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Patients will be randomized into two equal groups (1:1 allocation) using a computer-generated random number that will be enclosed in a sealed opaque envelope opened by an anesthesiologist, who is responsible for preparing the cardioplegia solution outside the OR and will not be involved in patient management or data collection.\n\nPatients, cardiothoracic surgeons, anesthesiologists, and data collectors will be blinded to group allocation until the end of the study.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This randomized double-blinded clinical trial will be reported following the tenets of the Declaration of Helsinki and the Consolidated Standards of Reporting Trials (CONSORT) 2025-updated statement.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 70}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-10-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2026-06-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-14', 'studyFirstSubmitDate': '2025-09-18', 'studyFirstSubmitQcDate': '2025-09-25', 'lastUpdatePostDateStruct': {'date': '2025-11-17', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-10-03', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2026-04-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'incidence of ventricular fibrillation (VF)', 'timeFrame': 'Perioperative', 'description': 'incidence of VF occurring after Aorta cross-clamp (ACC) removal'}], 'secondaryOutcomes': [{'measure': 'Troponin I (µg/L)', 'timeFrame': 'At immediate postoperatively, 12 and 24 hours postoperative', 'description': 'Troponin I to assess myocardial protection between the two cardioplegia solutions used.'}, {'measure': 'Number of defibrillator shocks', 'timeFrame': 'Perioperative', 'description': 'shocks required to terminate ventricular arrhythmia after ACC removal'}, {'measure': 'Total volume of cardioplegia solution (in ml).', 'timeFrame': 'Perioperative', 'description': 'cardioplegia volume given to the patient'}, {'measure': 'Total cross-clamp time', 'timeFrame': 'from cross clamp until removal of aorta cross clamp up to 6 hours', 'description': 'in minutes'}, {'measure': 'total CPB time', 'timeFrame': 'from starting CPB until weaning from bypass is completed up to 6 hours', 'description': 'in minutes'}, {'measure': 'Number of grafts', 'timeFrame': 'at the end of surgery up to 6 hours', 'description': 'anastomosis coronary grafts'}, {'measure': 'Time taken to cardiac arrest after cardioplegia infusion', 'timeFrame': 'from the start of cardioplegia administration until asystole up to one hour', 'description': 'time to asystole'}, {'measure': 'Left ventricular ejection fraction assessed both preoperative and after 24 hours postoperatively.', 'timeFrame': 'assessed both preoperative and after 24 hours postoperatively.', 'description': 'echo assessment'}, {'measure': 'Preoperative EURO II score', 'timeFrame': 'assessed preoperatively at the start of patient enrollment', 'description': 'EURO II score'}, {'measure': 'Inotropic support.', 'timeFrame': 'assessed after patient is transferred to intensive care up to 6 hours from start of surgery', 'description': 'the need for inotropes on transfer to intensive care'}, {'measure': 'Total time of inotropes or vasopressor requirement in hours', 'timeFrame': 'assessed after patient is weaned from inotropes up to one month', 'description': 'the need for inotropes in intensive care'}, {'measure': 'CK-MB (U/L) .', 'timeFrame': 'at immediate postoperatively, 12 and 24 hours after surgery', 'description': 'CK-MB (U/L) .'}, {'measure': 'Serum lactate level', 'timeFrame': 'at immediate postoperatively, 12 and 24 hours after surgery.', 'description': 'Serum lactate level'}, {'measure': 'Incidence of postoperative Myocardial infarction', 'timeFrame': 'assessed from icu admission until discharge up to one month', 'description': 'Incidence of postoperative Myocardial infarction'}, {'measure': 'Incidence of postoperative Atrial fibrillations', 'timeFrame': 'assessed from icu admission until ICU discharge up to one month', 'description': 'Incidence of postoperative Atrial fibrillations'}, {'measure': 'Time for weaning from mechanical ventilation', 'timeFrame': 'assessed from icu admission until ventilator weaning up to one month', 'description': 'from mechanical ventilation (in hours).'}, {'measure': 'ICU length of stay', 'timeFrame': 'assessed from icu admission until ICU discharge up to one month', 'description': 'in hours'}, {'measure': 'hospital length of stay (in days)', 'timeFrame': 'assessed from icu admission until home discharge up to one month', 'description': 'in days'}, {'measure': 'Mortality rate', 'timeFrame': 'assessed up to one month postoperatively', 'description': 'Mortality rate'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Custodiol', 'lidocaine', 'Bretschneider solution', 'Ventricular arrythmia'], 'conditions': ['CAD', 'Arrhythmia Ventricular']}, 'referencesModule': {'references': [{'pmid': '239002', 'type': 'BACKGROUND', 'citation': 'Bretschneider HJ, Hubner G, Knoll D, Lohr B, Nordbeck H, Spieckermann PG. Myocardial resistance and tolerance to ischemia: physiological and biochemical basis. J Cardiovasc Surg (Torino). 1975 May-Jun;16(3):241-60.'}, {'pmid': '35939196', 'type': 'BACKGROUND', 'citation': 'Barbero C, Pocar M, Marchetto G, Cura Stura E, Calia C, Dalbesio B, Filippini C, Salizzoni S, Boffini M, Rinaldi M, Ricci D. Single-Dose St. Thomas Versus Custodiol(R) Cardioplegia for Right Mini-thoracotomy Mitral Valve Surgery. J Cardiovasc Transl Res. 2023 Feb;16(1):192-198. doi: 10.1007/s12265-022-10296-z. Epub 2022 Aug 8.'}, {'pmid': '25298053', 'type': 'BACKGROUND', 'citation': 'Ferguson ZG, Yarborough DE, Jarvis BL, Sistino JJ. Evidence-based medicine and myocardial protection--where is the evidence? Perfusion. 2015 Jul;30(5):415-22. doi: 10.1177/0267659114551856. Epub 2014 Oct 8.'}, {'pmid': '35225070', 'type': 'BACKGROUND', 'citation': 'Chan J, Oo S, Butt S, Benedetto U, Caputo M, Angelini GD, Vohra HA. Network meta-analysis comparing blood cardioplegia, Del Nido cardioplegia and custodiol cardioplegia in minimally invasive cardiac surgery. Perfusion. 2023 Apr;38(3):464-472. doi: 10.1177/02676591221075522. Epub 2022 Feb 27.'}, {'pmid': '35735807', 'type': 'BACKGROUND', 'citation': 'Ghiragosian C, Harpa M, Stoica A, Sanziana FO, Balau R, Hussein HA, Elena GS, Neagoe RM, Suciu H. Theoretical and Practical Aspects in the Use of Bretschneider Cardioplegia. J Cardiovasc Dev Dis. 2022 Jun 2;9(6):178. doi: 10.3390/jcdd9060178.'}, {'pmid': '37801520', 'type': 'BACKGROUND', 'citation': "Kantathut N, Luangpatom-Aram K, Khajarern S, Leelayana P, Cherntanomwong P. Comparison of Single-Dose Cardioplegia in Valvular Heart Surgery: Lactated Ringer's-Based del Nido vs. Histidine-Tryptophan-Ketoglutarate Cardioplegia Solution. Braz J Cardiovasc Surg. 2023 Oct 6;38(6):e20220447. doi: 10.21470/1678-9741-2022-0447."}, {'pmid': '34922443', 'type': 'BACKGROUND', 'citation': 'Duan L, Hu GH, Wang E, Zhang CL, Huang LJ, Duan YY. Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study. BMC Cardiovasc Disord. 2021 Dec 18;21(1):604. doi: 10.1186/s12872-021-02411-w.'}, {'pmid': '7230856', 'type': 'BACKGROUND', 'citation': "Hearse DJ, O'Brien K, Braimbridge MV. Protection of the myocardium during ischemic arrest. Dose-response curves for procaine and lignocaine in cardioplegic solutions. J Thorac Cardiovasc Surg. 1981 Jun;81(6):873-9."}, {'pmid': '29444545', 'type': 'BACKGROUND', 'citation': 'Siddiqi S, Blackstone EH, Bakaeen FG. Bretschneider and del Nido solutions: Are they safe for coronary artery bypass grafting? If so, how should we use them? J Card Surg. 2018 May;33(5):229-234. doi: 10.1111/jocs.13539. Epub 2018 Feb 14.'}]}, 'descriptionModule': {'briefSummary': 'The Bretschneider solution, also known as Custodiol, has been widely used in open-heart surgery requiring cardiopulmonary bypass (CPB) since its introduction in 1970. Custodiol is widely favored by cardiac surgeons, being administered as a single dose, and is supposed to offer myocardial protection for up to three hours, permitting an uninterrupted surgical time, especially for intricate procedures The literature continues to debate the superiority of custodial and other cardioplegic solutions, such as the Del Nido and St. Thomas solutions, regarding both short-term and long-term outcomes. Clinical trials and daily practice showed that the use of custodial cardioplegic solution is associated with increased incidences of ventricular arrhythmias, and subsequently, the use of a defibrillator after Aortic Cross Clamp (ACC) removal at the end of CPB when compared to other types of cardioplegia solutions .One of the reasons for this difference mentioned in the literature is the lidocaine contained in other types of cardioplegic solutions. Lidocaine acts as a membrane stabilizer by blocking rapid sodium channels in the heart, thus preventing arrhythmias, in addition to its ability to inhibit calcium influx, which is the primary cause of ischemic-reperfusion injury.\n\nBased on these data, the investigators hypothesize that the increased incidence of Ventricular arrhythmias with the use of Custodiol compared to other solutions, such as St Thomas and Del Nido, may be attributed to the absence of lidocaine. Although Custodiol contains tryptophan as a membrane-stabilizing component, it may be beneficial to add lidocaine to the Custodiol mixture to decrease the incidence of VF after cross-clamp removal in adult patients undergoing elective CABG.', 'detailedDescription': "After Ethical Review Board of Fayoum University Hospital (FUH) approval and clinicaltrials.gov registration, all patients scheduled for isolated on-pump Coronary Artery Bypass Grafting (CABG) surgery in FUH starting from August 2025 will be enrolled in the study by signing a written informed consent until the sample size is fulfilled. This randomized double-blinded clinical trial will be reported following the tenets of the Declaration of Helsinki and the Consolidated Standards of Reporting Trials (CONSORT) 2025-updated statement.\n\nPatients will be randomized into two equal groups (1:1 allocation) using a computer-generated random number that will be enclosed in a sealed opaque envelope opened by an anesthesiologist, who is responsible for preparing the cardioplegia solution outside the OR and will not be involved in patient management or data collection.\n\nAccording to each envelope, the Study solution will be either standard Custodiol cardioplegia solution (manufactured by Dr. Franz Köhler Chemie GmbH, Bensheim, Germany), punctured at the injection port with a 10-cc syringe for blinding (Group C), or the modified solution prepared by adding 6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical) to each 1 L bag of Custodiol (Group L), using a 10-cc syringe. According to the patient's weight, one or two 1-L solutions will be prepared (calculated at 20 ml/kg, with a maximum of 2 L), kept at 5-8°C, and handed to the cardiothoracic anesthesia team when ordered. Patients, cardiothoracic surgeons, anesthesiologists, and data collectors will be blinded to group allocation until the end of the study.\n\nAll patients will be preoperatively examined and investigated by complete blood count, coagulation profile, liver and kidney functions, and electrolytes. A chest x-ray, Electrocardiography (ECG), echocardiography, Carotid arterial duplex, and Coronary angiography will be routinely ordered. Patients will receive an intramuscular injection of 10 mg morphine on the morning of the operation Upon arrival at OR, Standard monitoring will be applied, involving a 5-lead ECG and pulse oximetry. Blood pressure will be monitored through a 20-G cannula inserted into either the right or left radial artery under local anesthesia. Atracurium (0.5 mg/kg), midazolam (2-5 mg), fentanyl (2-5 μg/kg), and propofol (1-2 mg/kg) will be used to induce general anesthesia following pre-oxygenation.\n\nAfter tracheal intubation, patients will be mechanically ventilated with an Oxygen and air mixture, maintaining normocapnia confirmed by capnogram and arterial blood gas analysis. A urinary catheter, an esophageal temperature probe, and a right internal jugular triple-lumen central venous catheter will be inserted. Inhalational isoflurane (0.4 to 1 %) and atracurium infusion at 0.5 mg/kg/h will be used to maintain anesthesia and muscle relaxation. A 50-100 µg/kg/min propofol infusion will replace isoflurane inhalation during extracorporeal circulation.\n\nTo achieve an active clotting time of greater than 480 seconds, patients will receive intravenous heparin (300-500 units/kg body weight) prior to the initiation of cardiopulmonary bypass (CPB). An ascending aortic cannula and a two-stage right atrial cannula will be used to implement CPB. Before, during, and following CPB, mean arterial pressure will be adjusted to be higher than 60 mmHg (pump blood flow: 2.4 l/min/m2).\n\nMyocardial protection:\n\nThe antegrade approach will be utilized to deliver the cardioplegic solution through the coronary ostia or the aortic root, as appropriate. The cardioplegic solution will be either the classic Custodiol or the modified Custodiol according to the group allocation of each patient.\n\nA ready-blinded cardioplegia solution will be administered as a single dose of 20 mL/kg over 6-8 minutes at a temperature of 5-8 °C. An additional half dose of the same solution will be prepared and infused if the procedure exceeds 180 minutes after the initial dose is completed.\n\nMean arterial blood pressure will be maintained at 50-70 mmhg during the bypass period.\n\nBy completing distal anastomosis and before the ACC removal, all patients will be rewarmed to a core temperature of 36°C and have an arterial blood gas analysis that should have a normal PH (7.35-7.45), a normal potassium level (3.5 - 5.5) mg/dl, and a hemoglobin level above 10 g/dl, any abnormal value should be corrected before ACC removal. A 1.5 mg/kg lidocaine and 1 gram of Magnesium sulfate will be administered on the cardiopulmonary bypass machine just before the ACC release.\n\nAfter cross clamp removal, internal paddles will be used to defibrillate any ventricular fibrillation VF with 10 joule of energy.\n\nIf VF is resistant after three 10 j shocks, a 150 mg of Amiodarone will be administered and subsequent defibrillator shocks with escalating energy level 10, 20, and 30 joules will be used.\n\nProximal venous graft anastomoses will be carried out after applying a partial aortic cross clamp. Then, the patient will be gradually weaned from cardiopulmonary bypass after rewarming to normal core temperature and applying any needed inotropic or vasopressor support to maintain optimal cardiac output.\n\nProtamine sulfate will be administered after achieving hemodynamic stability to reverse the actions of heparin. The patient will be transferred to the postoperative cardiac surgery intensive care unit after completing hemostasis, drains, epicardial pacing wires, and wound closure.\n\nSample size calculation:\n\nthe sample size was calculated based on a previous study from Kammerer et.al, the incidence of ventricular fibrillation after ACC removal with Custodiol was 45.45 % and the incidence with conventional cardioplegic solution was 9.6 %. the investigators hypothesize that the addition of lidocaine to Custodiol will decrease the incidence of VF after ACC removal to a percentage similar to the conventional cardioplegic solution.\n\nTo account for this proportion difference, a minimal sample size of 31 patients in each group is needed to get a power level of 0.90 and an alpha level of 0.05. The calculated sample size will be increased to 35 in each group to allow for dropouts up to 10%. IBM SPSS software version 31 was used to estimate the required sample size.\n\nStatistical Analysis Statistical analysis will be performed using IBM SPSS software version 31. Descriptive statistics will be used to summarize participant demographics and clinical characteristics. Continuous variables will be reported as means ± standard deviations or medians with interquartile ranges, depending on normality of data assessed using the Shapiro-Wilk test. Categorical variables will be presented as frequencies and percentages. Independent t-tests or Mann-Whitney U tests will be applied to compare continuous variables between the two groups, while chi-square or Fisher's exact tests will be used for categorical variables as appropriate. Survival analysis with Kaplan Meier plot will be used for comparison of time to event variables. P-value less than 0.05 will be considered statistically significant."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients scheduled for elective Coronary artery bypass grafting surgery\n\nExclusion Criteria:\n\n* Emergency or Redo surgery.\n* Baseline rhythm other than sinus rhythm\n* Any degree of heart block, bundle branch block or hemiblock\n* Known allergy to lidocaine.\n* Chronic kidney disease.\n* Hepatic impairment.\n* Severe psychiatric illness.'}, 'identificationModule': {'nctId': 'NCT07205757', 'briefTitle': 'Adding Lidocaine to Custodiol Mixture', 'organization': {'class': 'OTHER', 'fullName': 'Fayoum University Hospital'}, 'officialTitle': 'Adding Lidocaine to Custodiol® Cardioplegia to Decrease Post-bypass Ventricular Arrhythmias in Adult Patients Undergoing Coronary Artery Bypass Grafting (CABG) Surgery; A Prospective Randomized Double-Blinded Clinical Trial.', 'orgStudyIdInfo': {'id': 'R 751'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Custodiol group', 'description': 'standard Custodiol cardioplegia solution (manufactured by Dr. Franz Köhler Chemie GmbH, Bensheim, Germany), punctured at the injection port with a 10-cc syringe for blinding', 'interventionNames': ['Drug: Custodiol Solution']}, {'type': 'EXPERIMENTAL', 'label': 'Lidocaine and Custodiol group', 'description': 'the modified solution prepared by adding 6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical) to each 1 L bag of Custodiol (Group L), using a 10-cc syringe.', 'interventionNames': ['Drug: Lidocaine Hydrochloride', 'Drug: Custodiol Solution']}], 'interventions': [{'name': 'Lidocaine Hydrochloride', 'type': 'DRUG', 'otherNames': ['Xylocaine'], 'description': '6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical)', 'armGroupLabels': ['Lidocaine and Custodiol group']}, {'name': 'Custodiol Solution', 'type': 'DRUG', 'otherNames': ['Bretschneider solution', 'HTK solution'], 'description': 'cardioplegia solution will be administered as a single dose of 20 mL/kg over 6-8 minutes at a temperature of 5-8 °C. An additional half dose of the same solution will be prepared and infused if the procedure exceeds 180 minutes after the initial dose is completed.', 'armGroupLabels': ['Custodiol group', 'Lidocaine and Custodiol group']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Al Fayyum', 'status': 'RECRUITING', 'country': 'Egypt', 'contacts': [{'name': 'Mohamed H Ragab, MD', 'role': 'CONTACT', 'email': 'mhr02@fayoum.edu.eg', 'phone': '01090050298', 'phoneExt': '+20'}, {'name': 'Mahdy A Abdelhady, MD', 'role': 'CONTACT', 'email': 'maa45@fayoum.edu.eg', 'phone': '01203632563', 'phoneExt': '+20'}], 'facility': 'Fayoum University Hospital', 'geoPoint': {'lat': 29.30995, 'lon': 30.8418}}], 'centralContacts': [{'name': 'Mohamed H Ragab, MD', 'role': 'CONTACT', 'email': 'mhr02@fayoum.edu.eg', 'phone': '01090050298', 'phoneExt': '+20'}, {'name': 'Mahdy A Abdelhady, MD', 'role': 'CONTACT', 'email': 'maa45@fayoum.edu.eg', 'phone': '01203632563', 'phoneExt': '+20'}], 'overallOfficials': [{'name': 'Mohamed H Ragab, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Lecturer of Anesthesiology'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fayoum University Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Lecturer of Anesthesiology', 'investigatorFullName': 'Mohamed Hasan Ragab', 'investigatorAffiliation': 'Fayoum University Hospital'}}}}