Clindamycin as an Alternative to Vancomycin in Patients Undergoing Aortic Cardiac Surgery With Extracorporeal Circulation (ECC)

Official title

Clindamycin as an Alternative to Vancomycin in Patients Undergoing Aortic Cardiac Surgery With Extracorporeal Circulation (ECC): a Prospective Single-center Pharmacokinetic Study

Overview

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.

Detailed description

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.

Interventions

• Drug Clindamycin
  Clindamycin used in the study corresponds to commercial forms of injectable clindamycin : KBI 600 mg/4 mL injectable solution, ampoule. * 1 ampoule contains 600 mg Clindamycin phosphate (expressed as Clindamycin base). * Excipients: edetate disodium, benzyl alcohol, sodium hydroxide, water for injection. * Dosage form: injectable solution 10minutes after injecting the first bolus of cefuroxime, clindamycin is reconstituted in 50 mL of 0.9% NaCl, then 900 mg of clindamycin is administered as a s

Primary outcome measures

• Plasma clindamycin concentrations [Time frame: H0 (at incision), then every hour, and at the end of surgery (defined as sternal closure)]

Secondary outcome measures (7)

• Determine the pharmacokinetic parameters of clindamycin under ECC [Time frame: At H0 (at incision), then every hour, and at the end of surgery (defined as sternal closure)]
• Determine the factors of variability in clindamycin pharmacokinetics for patients under ECC surgery [Time frame: Post-ECC at H+6 and H+24]
• Determining the diffusion of clindamycin in pericardial fatty tissue [Time frame: At the start of the operation (sternotomy) and when the pericardium is closed]
• Description of adverse events according to NCI CTCAE V5 criteria [Time frame: From first injection of clindamycin to end of hospitalization]
• Adherence to Good Clinical Practice clindamycin injection protocol [Time frame: 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) [Time frame: From inclusion to 3 months post-operatively (M3)]
• Post-op morbidity and mortality [Time frame: At 3 months (M3) post-operative (follow-up)]

Eligibility criteria

Inclusion criteria

• Adult ≥ 18 years of age,
• Cardiac surgery under ECC
• Surgery scheduled in the morning (added to the schedule at least 24 hours before the operation and starting at 8 a.m. in order to send blood tests during working hours).
• Written, informed consent from the patient before the start of the protocol.
• The patient must understand spoken and written French
• Negative pregnancy test and effective contraception (according to CTFG recommendations) during treatment for women of childbearing age
• Men of reproductive age using effective contraception (according to CTFG recommendations) during treatment
• Social security affiliation
• Patient able to understand the objectives of the study and comply with the requirements of the protocol

Exclusion criteria

• Known hypersensitivity/allergy to clindamycin, lincomycin, and any other excipient listed in the SmPC
• Known hypersensitivity/allergy to penicillins/drugs of the beta-lactam family
• Patient on antibiotics other than cefazolin prior to surgery
• Patient already on clindamycin at inclusion,
• BMI>35
• Aortic arch surgery
• Coronary artery bypass graft surgery
• Surgery for suspected endocarditis
• Patients with chronic renal failure with creatinine clearance < 60 mL/min and/or undergoing chronic dialysis
• Patients with hepatic insufficiency (prothrombin rate<50% excluding anticoagulant therapy) or Child B and C cirrhosis
• Immunosuppressed patients receiving triple antiviral therapy
• Pregnant or breast-feeding women
• Women or men of childbearing age without effective contraception
• Serious, uncontrolled concomitant bacterial infections (e.g. septic shock)
• Patients deprived of their liberty by judicial or administrative decision (guardianship, curatorship, safeguard of justice)
• Patient not registered with social security
• Participation in any other therapeutic study with an exclusion period still in effect at the time of inclusion, or planned participation in another therapeutic study while taking clindamycin
• Contraindications to cefazolin or any of the ancillary treatments
• Mental state rendering the patient incapable of understanding the entire study
• Patient being the investigator or any other member of the research team or being a relative of the investigator directly involved in the trial, including assistant physicians, pharmacists, nurses, and study coordinators

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

France · 1 center

• CHU Nantes — Nantes

Identifiers

NCT: NCT07267013 · RC24_0549 · 2025-521555-23-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗