Adding Lidocaine to Custodiol Mixture

NCT ID: NCT07205757

Last Updated: 2025-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-03

Study Completion Date

2026-06-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Based 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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

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.

According 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.

All 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.

After 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.

To 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).

Myocardial protection:

The 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.

A 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.

Mean arterial blood pressure will be maintained at 50-70 mmhg during the bypass period.

By 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.

After cross clamp removal, internal paddles will be used to defibrillate any ventricular fibrillation VF with 10 joule of energy.

If 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.

Proximal 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.

Protamine 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.

Sample size calculation:

the 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.

To 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.

Statistical 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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

CAD Arrhythmia Ventricular

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Patients, cardiothoracic surgeons, anesthesiologists, and data collectors will be blinded to group allocation until the end of the study.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Custodiol group

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 Type ACTIVE_COMPARATOR

Custodiol Solution

Intervention Type DRUG

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.

Lidocaine and Custodiol group

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.

Group Type EXPERIMENTAL

Lidocaine Hydrochloride

Intervention Type DRUG

6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical)

Custodiol Solution

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Lidocaine Hydrochloride

6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical)

Intervention Type DRUG

Custodiol Solution

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Xylocaine Bretschneider solution HTK solution

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* patients scheduled for elective Coronary artery bypass grafting surgery

Exclusion Criteria

* Emergency or Redo surgery.
* Baseline rhythm other than sinus rhythm
* Any degree of heart block, bundle branch block or hemiblock
* Known allergy to lidocaine.
* Chronic kidney disease.
* Hepatic impairment.
* Severe psychiatric illness.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Fayoum University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mohamed Hasan Ragab

Lecturer of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mohamed H Ragab, MD

Role: PRINCIPAL_INVESTIGATOR

Lecturer of Anesthesiology

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Fayoum University Hospital

Al Fayyum, , Egypt

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Egypt

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Mohamed H Ragab, MD

Role: CONTACT

01090050298 ext. +20

Mahdy A Abdelhady, MD

Role: CONTACT

01203632563 ext. +20

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Mohamed H Ragab, MD

Role: primary

01090050298 ext. +20

Mahdy A Abdelhady, MD

Role: backup

01203632563 ext. +20

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 239002 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35939196 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25298053 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35225070 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35735807 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37801520 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34922443 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7230856 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29444545 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R 751

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Etomidate Versus Propofol in CABG Surgery
NCT06068764 RECRUITING PHASE4
Neuroaxial Prophylaxis for CABG
NCT04244435 UNKNOWN EARLY_PHASE1