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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000513-39 | EudraCT Number |
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Future patients might benefit from a combination of linezolid (LIN) and clarithromycin (CLA) in the treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) due to possible synergistic activity as shown in in vitro experiments in different Mycobacteria strains. The investigators observed increased LIN serum levels in three cases after combining LIN and CLA of which the investigators described one in a case report (Bolhuis et al). The investigators suggest to conduct a prospective pharmacokinetic study in MDR- and XDR-TB patients to quantify the above described interaction between LIN and CLA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0mg, 250mg, and 500mg claritromycin | Other | Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Addition of different doses of clarithromycin. | Drug | At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks. At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA). | The AUCs of linezolid will be measured at 3 time points after addition of 3 different clarithromycin dosages. Samples were obtained before doseing and 1h, 2h, 3h, 4h, 8h, and 12h after administration of linezolid (and claritromycin depending on the period). | At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin). |
| Measure | Description | Time Frame |
|---|---|---|
| Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl. | At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline). | |
| Number of Patients With Adverse Events (AEs) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan-Willem C Alffenaar, PhD, PharmD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tuberculosis Center Beatrixoord | Haren | Provincie Groningen | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23520311 | Derived | Bolhuis MS, van Altena R, van Soolingen D, de Lange WC, Uges DR, van der Werf TS, Kosterink JG, Alffenaar JW. Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients. Eur Respir J. 2013 Dec;42(6):1614-21. doi: 10.1183/09031936.00001913. Epub 2013 Mar 21. |
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Not applicatble.
The study was performed at the Tuberculosis Centre Beatrixoord (University of Groningen, University Medical Center Groningen, Haren, The Netherlands).
Dates of recruitment: from december 2011 to november 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0mg, 250mg and 500mg Claritromycin | Patients receive 300mg linezolid twice a day during entire study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Linezolid Without Clarithromycin (1 wk) |
| |||||||||||||
| Linezolid + 250mg Claritromycin (wk 2&3) |
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| Linezolid + 500mg Claritromycin (wk 4&5) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Clarithromycin | Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered. Addition of different doses of clarithromycin. : At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks. At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA). | The AUCs of linezolid will be measured at 3 time points after addition of 3 different clarithromycin dosages. Samples were obtained before doseing and 1h, 2h, 3h, 4h, 8h, and 12h after administration of linezolid (and claritromycin depending on the period). | Posted | Median | Inter-Quartile Range | mg*h/L | At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin). |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0mg Claritromycin | Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered. Addition of different doses of clarithromycin. : At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks. At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. J.W.C. Alffenaar | University of Groningen, University Medical Center Groningen | +31-50-3614070 | 40378 | j.w.c.alffenaar@umcg.nl |
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| ID | Term |
|---|---|
| D018088 | Tuberculosis, Multidrug-Resistant |
| D054908 | Extensively Drug-Resistant Tuberculosis |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| ID | Term |
|---|---|
| D017291 | Clarithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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To assess short-term safety and tolerability when combining linezolid (LIN) with clarithromycin (CLA) by monitoring AEs, i.e. gastro-intestinal effects, hyperlactatemia, haematological abnormalities and neuropathy.
| Up to week 6 |
| Pharmacokinetic Parameters, e.g. Tmax, T1/2, Cmax, Cmin, Cl, of Anti-TB Drugs That Are Co-administered as Part of the Continued Standard Care. | At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin) |
| Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva. | The data will be used to clinically validate the analysis linezolid in saliva as surrogate marker for linezolid in plasma. | At week 3 (after co-administration of 250mg clarithromycin) |
|
|
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 250mg Clarithromycin |
| OG002 | 500mg Clarithromycin |
|
|
| Secondary | Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl. | Not Posted | At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline). |
| Secondary | Number of Patients With Adverse Events (AEs) | To assess short-term safety and tolerability when combining linezolid (LIN) with clarithromycin (CLA) by monitoring AEs, i.e. gastro-intestinal effects, hyperlactatemia, haematological abnormalities and neuropathy. | No serious adverse events | Posted | Number | participants | Up to week 6 |
|
|
|
| Secondary | Pharmacokinetic Parameters, e.g. Tmax, T1/2, Cmax, Cmin, Cl, of Anti-TB Drugs That Are Co-administered as Part of the Continued Standard Care. | Not Posted | At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin) |
| Secondary | Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva. | The data will be used to clinically validate the analysis linezolid in saliva as surrogate marker for linezolid in plasma. | Not Posted | At week 3 (after co-administration of 250mg clarithromycin) |
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | 250mg Clarithromycin | Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered. Addition of different doses of clarithromycin. : At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks. At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks. | 0 | 5 | 0 | 5 |
| EG002 | 500mg Clarithromycin | Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered. Addition of different doses of clarithromycin. : At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks. At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks. | 0 | 5 | 1 | 5 |
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| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| Organic Chemicals |