CLINDAMYCIN for Cardiac surgery with extracorporeal circulation (ECC)

Inclusion criteria

• {"criterion_text":"- Adult ≥ 18 years\n- Cardiac surgery under EEC\n- 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)\n- Written, informed consent from the patient before the start of the protocol\n- Patient's oral and written comprehension of French\n- Negative pregnancy test and effective contraception (according to CTFG recommendations) during treatment for women of childbearing age\n- Men of childbearing age with effective contraception (as recommended by the CTFG) during treatment\n- Social security affiliation\n- Patient able to understand the objectives of the study and comply with the requirements of the protocol"}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity/allergy to clindamycin, to lincomycin and any other excipient listed in the SmPC\n- Mental state rendering the patient unable of understanding the whole study\n- 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\n- Patient on antibiotics other than cefazolin prior to surgery\n- Patient already on clindamycin at inclusion\n- BMI>35\n- Aortic arch surgery\n- Coronary artery bypass graft surgery\n- Surgery for suspected endocarditis\n- Patients with hepatic insufficiency (prothrombin rate<50% excluding anticoagulant therapy) or Child B and C cirrhosis\n- Chronic renal failure patients with creatinine clearance < 60 mL/min and/or on chronic dialysis\n- Pregnant or breast-feeding women\n- Immunosuppressed patients receiving triple antiviral therapy\n- Women or men of childbearing age without effective contraception\n- Serious, uncontrolled concomitant bacterial infections (e.g. septic shock)\n- Patient deprived of their liberty by judicial or administrative decision (guardianship, curatorship, safeguard of justice)\n- Patient not registered with social security\n- 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\n- Known hypersensitivity/allergy to penicillins/drugs of the beta-lactam family\n- Contraindications to cefazolin or any of the auxiliary treatments"}

Primary endpoints

• {"endpoint_text":"- 1) a) Estimated free plasma clindamycin concentration throughout surgery. It will be estimated at incision, then every hour, and at the end of surgery. If clindamycin is re-injected during surgery (surgery > 4h), the free plasma clindamycin concentration will be estimated: just before re-injection, then at the end of re-injection, then every hour and at the end of surgery.","definition_or_measurement_approach":"Estimated free plasma clindamycin concentration measured at incision, then hourly and at end of surgery. If re-injection occurs (>4h surgery) samples: just before re-injection, end of re-injection, then hourly and at end of surgery."}
• {"endpoint_text":"- 1) b) 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.","definition_or_measurement_approach":"Free plasma concentration derived from measured total plasma clindamycin using an assumed bound fraction of 80–94%. Comparison to ECOFF (MIC) for S. aureus = 0.25 mg/L."}

Secondary endpoints

• {"endpoint_text":"- 1) a) Volume of distribution, clearance, elimination half-life, amount of intraoperative vascular filling (in ml), including blood transfusions: number and type of intraoperative LBP","definition_or_measurement_approach":"Pharmacokinetic parameters (Vd, clearance, t1/2) and intraoperative fluid/transfusion volumes including number and type of labile blood products recorded intraoperatively."}
• {"endpoint_text":"- 1) b) Collection of weight, height (calculation of BMI), collection of usual post-EEC biological data at H+6 and H+24 (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, EEC modalities (duration, type and quantity of priming solution, type of cardioplegia, body temperature), blood transfusion and volume reprocessed by Cell-Saver©","definition_or_measurement_approach":"Clinical and laboratory data collection including BMI, specified blood tests at H+6 and H+24, medication records for CYP3A4/5 modulators, details of extracorporeal circulation modality and transfusion/Cell-Saver volumes."}
• {"endpoint_text":"- 1) c) Tissue determination of clindamycin in pericardial fat and correlation with plasma levels","definition_or_measurement_approach":"Measurement of clindamycin concentration in pericardial fat tissue and correlation analysis with plasma concentrations."}
• {"endpoint_text":"- 2) Record of AEs and SAEs from first injection to discharge from hospital, and any clinical signs indicative of anaphylaxis on medical examination","definition_or_measurement_approach":"Safety monitoring: recording adverse events and serious adverse events from first injection until hospital discharge; specific recording of clinical signs of anaphylaxis."}
• {"endpoint_text":"- 3) 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","definition_or_measurement_approach":"Procedural timing data collection: injection durations, reinjection times/durations, and calculation of time interval between end of clindamycin injection and incision."}
• {"endpoint_text":"- 4) Rate of postoperative mediastinitis from Day0 to 3 months postoperative, defined as a postoperative 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","definition_or_measurement_approach":"Incidence of postoperative mediastinitis from day 0 to 3 months defined by need for repeat surgery and prolonged antibiotics; data collected from patient records and bacterial ecology collected."}
• {"endpoint_text":"- 5) Mortality at 3 months (telephone call)","definition_or_measurement_approach":"Follow-up telephone call at 3 months to assess survival status."}
• {"endpoint_text":"- 6) a) Volume of distribution, clearance, elimination half-life of cefazolin","definition_or_measurement_approach":"Pharmacokinetic parameters (Vd, clearance, t1/2) for cefazolin measured as specified."}
• {"endpoint_text":"- 6) b) Tissue determination of cefazolin in pericardial fat and correlation with plasma levels of cefazolin and clindamycin","definition_or_measurement_approach":"Measurement of cefazolin concentration in pericardial fat and correlation with plasma cefazolin and clindamycin levels."}

France

Earliest CTIS Part Ii Submission Date

06-08-2025

Latest Decision Or Authorization Date

07-01-2026

Processing Time Days

154

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nantes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France