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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-521555-23-00 | EU Trial (CTIS) Number |
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Antibiotic prophylaxis is essential for all types of cardiac surgery under Extracorporeal Circulation (ECC), in order to reduce the incidence of surgical site infection (SSI). However, many patients are allergic to beta-lactam antibiotics. All the more, vancomycin antibiotic recommended as replacement is not without adverse effects and frequently administered in an inappropriate manner in terms of pre-intervention timing, linked to its complex use on peripheral venous lines complicated by venotoxicity. Non-compliance with the correct use of antibiotic prophylaxis in surgery is responsible for nosocomial infections, which have an impact on both the patient and the healthcare establishment in terms of costs, particularly in cardiac surgery.
Drug pharmacokinetics are more complex under bypass surgery (high volume of distribution), and studies are needed to determine the correct administration and diffusion of drugs.
In this respect, clindamycin is an antibiotic already used in antibiotic prophylaxis for other surgeries (thoracic, orthopedic...) in cases of allergy to beta-lactam antibiotics, but to date there are no studies examining the pharmacokinetics of this molecule in the context of cardiac surgery under ECC.
The aim of this protocol is to demonstrate the feasibility of using clindamycin in patients undergoing ECC surgery, by verifying that the plasma concentration of clindamycin exceeds the minimum inhibition concentration (MIC) of the main bacteria involved in mediastinitis throughout the surgical procedure.
ECC is indispensable for cardiac surgery, but this assistance modifies the pharmacological properties of drugs, with a particular increase in the volume of distribution of antibiotics such as clindamycin. All these factors lead to an increase in the dosage of certain drugs and more frequent injections.
Robust data on percutaneous clindamycin treatment would therefore enable to improve the management of this type of patient, with real impact.
There are currently no pharmacological studies justifying the use of clindamycin to combat nosocomial infections in cardiac surgery, despite the fact that its anti-bacterial spectrum is identical to that of the antibiotics currently used in patients (methicillin-sensitive Staphylococcus aureus (MSSA)).
Clindamycin is simpler to use and does not induce venotoxicity. The fact that the patient is undergoing bypass surgery means that pharmacokinetic studies can be carried out with several blood samples taken from the arterial pressure catheter routinely inserted in all surgical patients, in order to limit the volume of blood taken and avoid any discomfort for the patient. This would make it possible to check the plasma stability of this antibiotic over several periods, with reinjections if necessary (if surgery > 4h).
The hypotheses are that clindamycin (i) is simple to use, (ii) has correct and stable diffusion kinetics in patients undergoing scheduled cardiac surgery with ECC (iii) is well tolerated by patients (iv) has an estimated free plasma concentration above the epidemiological threshold Minimal Inhibition Concentration (MIC) of Staphylococcus aureus and therefore provides sufficient protection against SSI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clindamycin | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clindamycin | Drug | Clindamycin used in the study corresponds to commercial forms of injectable clindamycin : KBI 600 mg/4 mL injectable solution, ampoule.
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| Measure | Description | Time Frame |
|---|---|---|
| Plasma clindamycin concentrations | To demonstrate the feasibility of using clindamycin in patients undergoing ECC and to assure that plasma clindamycin concentrations remain above the minimum inhibition concentration (MIC) of the main bacteria involved in mediastinitis, estimated free plasma clindamycin concentration will be verify throughout surgery. The free plasma concentration of clindamycin is estimated by measuring the total plasma concentration of clindamycin, based on a bound fraction of 80 to 94%.The epidemiological threshold MIC for S. aureus (ECOFF = 0.25 mg/L for clindamycin) was chosen for comparison with clindamycin concentrations, given that this bacterium is the main one implicated in mediastinitis. | H0 (at incision), then every hour, and at the end of surgery (defined as sternal closure) |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the pharmacokinetic parameters of clindamycin under ECC | Volume of distribution, clearance, elimination half-life, quantity of intra-operative vascular filling (in ml) including blood transfusions: number and type of intra-operative LBS (labile blood products) | At H0 (at incision), then every hour, and at the end of surgery (defined as sternal closure) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julien CADIET, MD | Contact | +33(0)2.44.76.86.86 | +33 | julien.cadiet@chu-nantes.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Nantes | Recruiting | Nantes | France | 44000 | France |
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| ID | Term |
|---|---|
| D002981 | Clindamycin |
| ID | Term |
|---|---|
| D008034 | Lincomycin |
| D055231 | Lincosamides |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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Phase 2 interventional study, single-center, prospective and uncontrolled study conducted at Nantes University Hospital in the CTCV (Thoracic and Cardiovascular Surgery) anesthesia and intensive care unit.
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| Determine the factors of variability in clindamycin pharmacokinetics for patients under ECC surgery | Collection of weight, height (calculation of BMI), collection of usual post-CEC biological data (creatinemia with calculation of GFR, ASAT/ALAT, total and conjugated bilirubinemia, PAL, γ-GT, protidemia with addition of α-1 acid glycoprotein at induction), qualitative record of CYP3A4/5 inducer/inhibitor drugs, CEC modalities (duration, type and quantity of priming solution, type of cardioplegia, body temperature), blood transfusion and volume reprocessed by Cell-Saver©. | Post-ECC at H+6 and H+24 |
| Determining the diffusion of clindamycin in pericardial fatty tissue | Tissue determination of clindamycin in pericardial fat and correlation with plasma levels (biocollection, ancillary study | At the start of the operation (sternotomy) and when the pericardium is closed |
| Description of adverse events according to NCI CTCAE V5 criteria | Recording of AEs and SAEs, collection of all clinical signs indicative of anaphylaxis on medical examination | From first injection of clindamycin to end of hospitalization |
| Adherence to Good Clinical Practice clindamycin injection protocol | Recording of clindamycin injection duration, time of reinjections and duration of reinjections, calculation of delta between time of end of clindamycin injection and start of surgical incision | From first injection of clindamycin to the end of surgery (defined as sternal closure) |
| Rate of post-operative mediastinitis (up to 3 months post-operatively) | Rate of post-operative mediastinitis defined as a post-operative nosocomial cardiac surgery infection at the surgical site (mediastinum) requiring repeat surgery (drainage lavage) and prolonged antibiotic therapy. Collection of data from the patient's file, as the patient was systematically referred to the Nantes University Hospital. Collection of bacterial ecology | From inclusion to 3 months post-operatively (M3) |
| Post-op morbidity and mortality | Mortality at 3 months (telephone call) | At 3 months (M3) post-operative (follow-up) |
| D006571 |
| Heterocyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |