NCT03126890

Brief Summary

Linezolid is the second line agent in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative option against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. However, Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may prone to experience anemia, thrombocytopenia, and leukopenia. Long-term use may also result in lactic acidosis, peripheral neuropathy and optic neuropathy due to mitochondrial toxicity. Thus, this study will analysis the medical charts in National Taiwan University Hospital (NTUH) from 2011 to 2016 to get the population demographics who use linezolid and analysis the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Simultaneously, the investigators also use therapeutic drug monitoring (TDM) to prospectively evaluate the association of linezolid blood concentration and clinical efficacy and safety. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,000

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Nov 2016

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2016

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

November 30, 2016

Completed
5 months until next milestone

First Posted

Study publicly available on registry

April 25, 2017

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

February 10, 2022

Status Verified

February 1, 2022

Enrollment Period

7.2 years

First QC Date

November 30, 2016

Last Update Submit

February 8, 2022

Conditions

MyelosuppressionLactic AcidosisPeripheral Neuropathy

Keywords

Pharmacokinetics,adverse eventsLinezolidTherapeutic drug monitoringMyelosuppressionLactic acidosisPeripheral neuropathy

Outcome Measures

Primary Outcomes (6)

  • Clinical efficacy

    Clinical efficacy definition: Cure: biological eradication or clinical improvement. (Biological eradication: Eradication of bacterial culture prior to study drug) (Clinical improvement: White blood cell (WBC), C reactive protein (CRP) back to normal range (WBC: 3500 - 9000/mm3; CRP: \< 1 mg/dL) or without sepsis symptom (body temperature, pulse, heart rate returned to normal)) Intermittent cure: same bacteria culture positive (with same minimum inhibitory concentration (MIC) data) within 2 weeks after linezolid treatment ends. Failure: persistent bacteria culture after linezolid treatment or unresolved clinical sign and symptoms. Indeterminate outcome: loss of follow up or discontinue linezolid due to adverse drug reaction

    Observation periods: entire linezolid treatment course until 30 days after the completion of treatment, loss of follow up, death or December 2020 (up to 4 years).

  • Safety - thrombocytopenia

    Definition of thrombocytopenia: platelet count \< 100,000/mm3 and platelet count of \< 75% of the baseline counts.

    Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).

  • Safety - anemia

    Definition of anemia: Hemoglobin (Hb) \< 10 g/dL and Hb level of \< 75% of the baseline level.

    Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).

  • Safety - leukopenia

    Definition of leukopenia: WBC count \< 3000/mm3 and WBC count of \< 50% of baseline count.

    Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).

  • Safety - lactic acidosis

    Definition of lactic acidosis: 1. Definite lactic acidosis: lactic acid \> 4 mmol/L and blood potential of hydrogen (pH) value \< 7.35 2. Probable lactic acidosis: lactic acid \> 4 mmol/L without or not achieved pH value data

    Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).

  • Safety - peripheral neuropathy

    Definition of peripheral neuropathy (PN): 1. Definite PN: with nerve conduction velocity test (+) 2. Probable PN: patient reported symptoms

    Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).

Study Arms (2)

Linezolid TDM (prospective)

Adult patients received linezolid at NTUH. This prospective cohort study will draw blood from every patient to measure the linezolid blood concentration. After blood concentration analysis by high pressure liquid chromatography (HPLC), the investigator will report the concentration to clinicians and dose adjustment is judged by clinician (not the investigators).

Linezolid observation (retrospective)

Adult patients received linezolid at NTUH.

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with oral or intravenous linezolid

You may not qualify if:

  • Retrospective study 1. Patients without baseline complete blood count (CBC) data (RBC or Hb, WBC, platelet) before linezolid treatment. Prospective study
  • \. Patients with severe disease status (assess by clinicians) might die within 2 days or treatment duration less than 2 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Taiwan University Hospital

Taipei, Test2, test3, Taiwan

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood for drug concentration monitoring

MeSH Terms

Conditions

Acidosis, LacticPeripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

AcidosisAcid-Base ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesNeuromuscular DiseasesNervous System Diseases

Study Officials

  • Shu-Wen Lin

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Shu-Wen Lin, Pharm.D

CONTACT

886-2-33668782shuwenlin@ntu.edu.tw

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2016

First Posted

April 25, 2017

Study Start

November 1, 2016

Primary Completion

December 31, 2023

Study Completion

December 31, 2023

Last Updated

February 10, 2022

Record last verified: 2022-02

Locations

TW(1)