MyelosuppressionNCT03126890
Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment Response and Adverse Reactions
An observational study of Myelosuppression and Lactic Acidosis, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Myelosuppression, Lactic Acidosis, Peripheral Neuropathy
- How many people
- 1,000 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Nov 2016to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with oral or intravenous linezolid
Who may be able to join
None listed.
Who cannot join
- Retrospective study 1. Patients without baseline complete blood count (CBC) data (RBC or Hb, WBC, platelet) before linezolid treatment. Prospective study
- 1. Patients with severe disease status (assess by clinicians) might die within 2 days or treatment duration less than 2 days
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, Test2, test3
Shu-Wen Lin, 02 - 33668782, shuwenlin@ntu.edu.tw
About this study
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.
Read the detailed description
The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP) has caused significant medical issue. With limited antimicrobial agents available, it has been an increasing challenge in infection control and disease treatment. Linezolid is the second line antibiotics in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. Linezolid has almost 100% of bioavailability. It has excellent tissue penetration. It metabolized via non-enzymatic oxidation. Two major metabolites, aminoethoxyacetic acid (chemical name) and hydroxyethyl glycine (chemical name), are final forms before excreted through kidneys. Even though the manufacturer does not recommend dosing adjustment for patients with renal or hepatic dysfunction, recent studies demonstrated accumulation of linezolid and 2 metabolites in the body. Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may present higher plasma linezolid concentration. Patients may experience anemia, thrombocytopenia, and leukopenia under long-term use of linezolid. However, there is lack of study on lactic acidosis, peripheral neuropathy, and optic neuropathy due to mitochondrial toxicity.
This study has two parts. This study will analysis the medical charts in NTUH from 2011 to 2016 to get the population demographics who use linezolid and the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Then, followed by a prospective study which aim is to monitor the plasma peak and trough concentration of linezolid (total and free drug) and 2 metabolites by different sample collecting method (plasma, dry blood spot; DBS). If clinical necessity, the investigators may also monitor tissue fluid concentration. Clinical response and toxicity were monitored by liquid chromatography (LC) analysis. The investigators plan to evaluate the association between plasma concentration and toxicity including bone marrow suppression, peripheral neuropathy, and lactic acidosis. It is important to determine if dose adjustment in patients with renal and/or hepatic dysfunction is required. Simultaneously, the investigators want to develop DBS method which can ease patients' uncomfortable sense and simplify the drug monitor process. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.
- Conditions
- Myelosuppression, Lactic Acidosis, Peripheral Neuropathy
- Keywords
- Pharmacokinetics,adverse events, Linezolid, Therapeutic drug monitoring, Myelosuppression, Lactic acidosis, Peripheral neuropathy
- Medical subject headings
- Acidosis, Lactic, Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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:
- Definite lactic acidosis: lactic acid > 4 mmol/L and blood potential of hydrogen (pH) value < 7.35
- Probable lactic acidosis: lactic acid > 4 mmol/L without or not achieved pH value data
Measured: 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):
- Definite PN: with nerve conduction velocity test (+)
- Probable PN: patient reported symptoms
Measured: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2017
- Study start1 Nov 2016
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelosuppressionStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shu-Wen Lin, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03126890
- Sponsor's protocol ID
- 201610008RINB
- Status last verified
- Feb 2022
- First submitted
- 30 Nov 2016
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment Response and Adverse Reactions
- ClinicalTrials.gov ID
- NCT03126890
- Acronym / sponsor ID
- 201610008RINB
- Conditions
- Myelosuppression, Lactic Acidosis, Peripheral Neuropathy
- Keywords
- Pharmacokinetics,adverse events, Linezolid, Therapeutic drug monitoring, Myelosuppression, Lactic acidosis, Peripheral neuropathy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 25 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP) has caused significant medical issue. With limited antimicrobial agents available, it has been an increasing challenge in infection control and disease treatment. Linezolid is the second line antibiotics in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. Linezolid has almost 100% of bioavailability. It has excellent tissue penetration. It metabolized via non-enzymatic oxidation. Two major metabolites, aminoethoxyacetic acid (chemical name) and hydroxyethyl glycine (chemical name), are final forms before excreted through kidneys. Even though the manufacturer does not recommend dosing adjustment for patients with renal or hepatic dysfunction, recent studies demonstrated accumulation of linezolid and 2 metabolites in the body. Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may present higher plasma linezolid concentration. Patients may experience anemia, thrombocytopenia, and leukopenia under long-term use of linezolid. However, there is lack of study on lactic acidosis, peripheral neuropathy, and optic neuropathy due to mitochondrial toxicity.
This study has two parts. This study will analysis the medical charts in NTUH from 2011 to 2016 to get the population demographics who use linezolid and the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Then, followed by a prospective study which aim is to monitor the plasma peak and trough concentration of linezolid (total and free drug) and 2 metabolites by different sample collecting method (plasma, dry blood spot; DBS). If clinical necessity, the investigators may also monitor tissue fluid concentration. Clinical response and toxicity were monitored by liquid chromatography (LC) analysis. The investigators plan to evaluate the association between plasma concentration and toxicity including bone marrow suppression, peripheral neuropathy, and lactic acidosis. It is important to determine if dose adjustment in patients with renal and/or hepatic dysfunction is required. Simultaneously, the investigators want to develop DBS method which can ease patients' uncomfortable sense and simplify the drug monitor process. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with oral or intravenous linezolid
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- Retrospective study 1. Patients without baseline complete blood count (CBC) data (RBC or Hb, WBC, platelet) before linezolid treatment. Prospective study
- 1. Patients with severe disease status (assess by clinicians) might die within 2 days or treatment duration less than 2 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Clinical efficacy
Time frame: 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).
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
Safety - thrombocytopenia
Time frame: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
Definition of thrombocytopenia: platelet count < 100,000/mm3 and platelet count of < 75% of the baseline counts.
Safety - anemia
Time frame: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
Definition of anemia: Hemoglobin (Hb) < 10 g/dL and Hb level of < 75% of the baseline level.
Safety - leukopenia
Time frame: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
Definition of leukopenia: WBC count < 3000/mm3 and WBC count of < 50% of baseline count.
Safety - lactic acidosis
Time frame: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
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
Safety - peripheral neuropathy
Time frame: Observation periods: entire linezolid treatment course until resolution of side effect, loss of follow up, death or December 2020 (up to 4 years).
Definition of peripheral neuropathy (PN): 1. Definite PN: with nerve conduction velocity test (+) 2. Probable PN: patient reported symptoms
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shu-Wen Lin principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myelosuppression and Lactic Acidosis, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shu-Wen Lin, Pharm.D (886-2-33668782, shuwenlin@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy (time frame: 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).). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.