Clindamycin as an alternative to vancomycin in patients undergoing aortic cardiac surgery with extracorporeal circulation (ECC): a prospective single-center pharmacokinetic study _ CLINDAPASS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

21 Apr 2026 → ongoing

Decision date (initial)

2025-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AOI recherche clinique 2024 CHU Nantes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Prophylaxis

Demonstrate the feasibility of using clindamycin in patients undergoing EEC surgery by verifying that plasma clindamycin concentrations remain above the minimum inhibition concentration (MIC) of the main bacteria involved in mediastinitis throughout the surgical procedure

Secondary objectives 9

1. 1) a) To determine the pharmacokinetic parameters of clindamycin under EEC
2. 1) b) To Determine the factors of variability in clindamycin pharmacokinetics for patients undergoing bypass surgery
3. 1) c) To determine the diffusion of clindamycin in pericardial fatty tissue
4. 2) Description of adverse events according to NCI CTCAE V5 criteria
5. 3) Adherence to clindamycin injection protocol according to good clinical practice
6. 4) Rate of post-operative mediastinitis (up to 3 months post-operatively)
7. 5) Post-operative morbidity and mortality (up to 3 months post-operatively)
8. 6) a) To determine the pharmacokinetic parameters of cefazolin under EEC
9. 6) b) To determine the diffusion of cefazolin in pericardial fatty tissue

Conditions and MedDRA coding

Patients undergoing cardiac surgery with extracorporeal circulation (ECC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adult ≥ 18 years
2. Cardiac surgery under EEC
3. 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)
4. Written, informed consent from the patient before the start of the protocol
5. Patient's oral and written comprehension of French
6. Negative pregnancy test and effective contraception (according to CTFG recommendations) during treatment for women of childbearing age
7. Men of childbearing age with effective contraception (as recommended by the CTFG) during treatment
8. Social security affiliation
9. Patient able to understand the objectives of the study and comply with the requirements of the protocol

Exclusion criteria 20

1. Known hypersensitivity/allergy to clindamycin, to lincomycin and any other excipient listed in the SmPC
2. Pregnant or breast-feeding women
3. Women or men of childbearing age without effective contraception
4. Serious, uncontrolled concomitant bacterial infections (e.g. septic shock)
5. Patient deprived of their liberty by judicial or administrative decision (guardianship, curatorship, safeguard of justice)
6. Patient not registered with social security
7. 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
8. Known hypersensitivity/allergy to penicillins/drugs of the beta-lactam family
9. Contraindications to cefazolin or any of the auxiliary treatments
10. Mental state rendering the patient unable of understanding the whole study
11. 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
12. Patient on antibiotics other than cefazolin prior to surgery
13. Patient already on clindamycin at inclusion
14. BMI>35
15. Aortic arch surgery
16. Coronary artery bypass graft surgery
17. Surgery for suspected endocarditis
18. Patients with hepatic insufficiency (prothrombin rate<50% excluding anticoagulant therapy) or Child B and C cirrhosis
19. Chronic renal failure patients with creatinine clearance < 60 mL/min and/or on chronic dialysis
20. Immunosuppressed patients receiving triple antiviral therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. 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.

Secondary endpoints 9

1. 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
2. 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©
3. 1) c) Tissue determination of clindamycin in pericardial fat and correlation with plasma levels
4. 2) Record of AEs and SAEs from first injection to discharge from hospital, and any clinical signs indicative of anaphylaxis on medical examination
5. 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
6. 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
7. 5) Mortality at 3 months (telephone call)
8. 6) a) Volume of distribution, clearance, elimination half-life of cefazolin
9. 6) b) Tissue determination of cefazolin in pericardial fat and correlation with plasma levels of cefazolin and clindamycin

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Julien CADIET

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Dr Julien CADIET

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications