Multicenter before-and-after comparative study on the safety of therapeutic drug monitoring for linezolid-induced thrombocytopenia

JRCT ID: jRCTs031240652

Registered date:31/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Gram-positive bacterial infections
• Date of first enrollment: 31/01/2025
• Target sample size: 60
• Study type: Interventional
• Intervention(s): Linezolid tablets/injections are initiated as standard treatment based on the physician's decision (typically 1200 mg/day). In cases where oral administration is not feasible due to gastrointestinal absorption or other factors, linezolid will be administered via injection. In patients who have provided consent, the principal, responsible, or sub-investigators will conduct joint consultations. Linezolid dosage is adjusted based on therapeutic drug monitoring to maintain serum linezolid concentrations within the range of 2-8 micro gram /mL (the maximum daily dose is 1200 mg). With the initiation of linezolid defined as day 0, initial therapeutic drug monitoring is conducted on day 1, and the second measurement is taken on days 2-4 (if blood tests cannot be performed on day 1 due to the timing of trial enrollment, the first measurement will be taken on days 2 to 4). Subsequently, therapeutic drug monitoring is conducted approximately once a week as needed (if the dosage is adjusted, serum concentrations will be reassessed on day 3+-1 after the change). Serum from routine blood tests (250 micro liter per measurement) is used for measuring linezolid concentrations. For blood concentration measurements, samples should be collected within 30 minutes before the next linezolid dose (the timing of sample collection will be coordinated with the relevant clinical department). The LM1010 high-performance liquid chromatograph is used for measurement, and analysis is performed using simulation software (Pycsim). The predicted serum concentration on day 3+-1 after the dosage adjustment, expected to be at steady state, is simulated based on the measured trough value. The linezolid dosage is then assessed based on the simulation results. Each dose should not exceed 600 mg, and the total daily dose should not exceed 1200 mg. Dose adjustments should be made in increments of 150 mg (2.5 mg/kg for pediatric patients). If multiple dosing regimens maintain the trough concentration within the range of 2-8 micro gram /mL, the regimen with the lowest estimated trough concentration should be selected. Based on the simulation results, the principal, responsible, or sub-investigators will assess the linezolid dosage, and the final dosage will be determined in consultation with the attending or primary physician of the patient. Subsequently, the principal, responsible, or sub-investigators will prescribe linezolid. The duration of linezolid treatment should be determined based on the standard treatment period for the targeted infection and the patient's condition. Research assistants will not be involved in determining the dosage or other tasks related to the study's evaluation criteria.

Outcome(s)

• Primary Outcome: Time to onset of thrombocytopenia after linezolid initiation

Secondary Outcome

1. Time to onset of severe thrombocytopenia after linezolid initiation
2. Incidence rate of severe thrombocytopenia during the linezolid treatment period
3. Incidence rate of thrombocytopenia on days 3, 7+-1, 14+-2, and 28+-2 from linezolid initiation
4. Incidence rate of severe thrombocytopenia on days 3, 7+-1, 14+-2, and 28+-2 from linezolid initiation
5. Mortality rate at 30 days from linezolid initiation
6. Treatment success rate at 30 days from linezolid initiation
7. Discontinuation rate of linezolid due to adverse events
8. Duration of linezolid administration
9. Serum concentration of linezolid
10. Daily dose and cost of linezolid administration
11. Immature platelet count and reticulocyte count on days 3, 7+-1, 14+-2, and 28+-2 from linezolid initiation

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

Intervention Group
1. Patients receiving inpatient or outpatient care at Tsukuba University Hospital, Hitachi General Hospital, or Tsukuba Medical Center Hospital
2. Patients scheduled to receive linezolid for 7 days or more
3. Patients who underwent blood tests between 3 days prior to and the day of linezolid initiation
4. Patients with platelet count or more 75000/micro liter at linezolid initiation
5. Patients within 3 days after linezolid initiation
6. Patients who provided written informed concent either personally or through a proxy (limited to relatives)

Control Group
1. Patients who received linezolid for 7 days or more at Tsukuba University Hospital, Hitachi General Hospital, or Tsukuba Medical Center Hospital between January 2015 and May 2023
2. Patients who underwent blood tests between 3 days prior to and the day of linezolid initiation
3. Patients with platelet count or more 75000/micro liter at linezolid initiation

Exclude criteria

1) Patients deemed inappropriate for this study by the investigators
2) Patients who refused enrollment in the opt-out study (control group)

Related Information

• Primary Sponsor: Suzuki Hiromichi
• Source(s) of Monetary Support: Hitachi High-Tech Science corporation,Research funding of the department of infectious diseases, tsukuba university hospital