Vancomycin Concentration Analysis in Post-Cardiac Surgery Patients

NCT07087301 | Completed

• 1 other identifier: 2023-Ethics79
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

The benefits of antimicrobial prophylaxis for cardiac surgery have been clearly demonstrated in placebo-controlled studies. Prophylactic intravenous antibiotics are therefore administered, with agent selection directed against the most common skin-colonising and gram-negative bacteria. Controversy persists regarding the optimal antimicrobial choice and duration of administration for cardiac surgery. In settings with a high incidence of methicillin-resistant Staphylococcus aureus (MRSA), administration of cefazolin or vancomycin for prophylaxis is considered reasonable (Class IIB recommendation, Level of Evidence C). Vancomycin, a glycopeptide antibiotic, is widely used to treat serious gram-positive infections, including those caused by MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE). Extensive pharmacokinetic/pharmacodynamic (PK/PD) studies reveal marked variability in population PK parameters across patient groups; clearance variability may reach 45 % and volume of distribution variability 48 %. Oral vancomycin absorption is poor (≈5 % bioavailability), yet luminal concentrations remain sufficiently high for efficacy against Clostridioides difficile-associated pseudomembranous colitis. Inter-individual PK variability is substantial; two- or three-compartment models are typically employed. Protein binding ranges from 30 % to 50 %. Approximately 90 % of the dose is eliminated unchanged via the kidneys; biliary elimination is minimal. The elimination half-life is 4-7 h in individuals with normal renal function and is prolonged in patients \>65 years or with renal impairment. Obesity, age, renal function, concomitant medications, disease state, and peri-operative interventions can all influence vancomycin clearance and apparent volume of distribution, potentially yielding sub- or supra-therapeutic serum concentrations. To characterise current therapeutic drug monitoring (TDM) practices for vancomycin in cardiac-surgery patients undergoing cardiopulmonary bypass, this retrospective study combined multimodal data to develop a prognostic model predicting high- or low-risk vancomycin serum levels post-operatively. Model performance was evaluated to provide an evidence base for individualised dosing strategies aimed at optimising efficacy and minimising adverse effects. Pharmacokinetic datasets from post-cardiac-surgery patients receiving cardiopulmonary bypass were analysed to identify determinants of vancomycin blood concentrations. Integration of baseline characteristics and medication records supports early intervention guidance for individualised vancomycin dosing and optimisation of anti-infective therapy.

Conditions

Cardiac Surgery Requiring Cardiopulmonary Bypass

Outcome Measures

Primary Outcomes (1)

• Vancomycin trough concentration

  Pre-dose vancomycin serum concentration at steady state

  Day 3 pre-dose

Secondary Outcomes (2)

• Cardiopulmonary Bypass Duration

  Intra-operative (from initiation to termination of bypass)

• Creatinine Clearance

  Baseline

Study Arms (1)

nephrotoxicity risk group

nephrotoxicity risk group (≥20 mg/L vs \<20 mg/L, n=350). A dual-model framework was established based on vancomycin's therapeutic window (10-20 mg/L): the first model (for nephrotoxicity risk prediction) defined high concentration as ≥20 mg/L and control as \<20 mg/L to identify risk factors for vancomycin accumulation.

Other: subtherapeutic concentration risk group; Drug: subtherapeutic concentration risk group

Interventions

subtherapeutic concentration risk group OTHER

The second model (for subtherapeutic concentration risk prediction) defined low concentration as trough \<10 mg/L and target as 10-20 mg/L to analyze predictors of target concentration attainment.

nephrotoxicity risk group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients requiring cardiac surgery for conditions such as valvular heart disease who received postoperative vancomycin for infections.

You may qualify if:

• Undergoing cardiac surgery with cardiopulmonary bypass
• Received intravenous vancomycin postoperatively for infection prophylaxis or treatment

You may not qualify if:

• Age \<18 years
• Missing data on weight, height, or serum creatinine during vancomycin therapy
• No vancomycin trough plasma concentration recorded

Sponsors & Collaborators

• Pengqiang Du: lead

Study Sites (1)

Fuwai Central China Cardiovascular Hospital

Zhengzhou, Henan, 450046, China

Location

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Chief Pharmacist

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: July 25, 2025
• Study Start: January 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 25, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)