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The problem of interest is that doctors are looking for new antibiotic treatments for bone and joint infections. Treatment for bone and joint infection is not standardized, which allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called S. aureus is the most common cause of bone and joint infection. Methicillin resistant S. aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is increasingly common in U.S. and non-U.S. medical centers. This problem will be studied by investigating whether an antibiotic called tedizolid is tolerable, safe and effective to treat bone and joint infections.
The problem of interest is that doctors are looking for new antibiotic treatments for bone and joint infections. Treatment for bone and joint infection is not standardized, which allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called S. aureus is the most common cause of bone and joint infection. Methicillin resistant S. aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is increasingly common in U.S. and non-U.S. medical centers. Trauma-associated bone and joint infection is also a common problem. Victims of major trauma often suffer bone fractures, which require temporary or permanent use of metal or other synthetic devices such as external-fixation pins, plates, and screws. These synthetic devices can also get infected and cause bone and joint infections.
This problem will be studied by investigating whether an antibiotic called tedizolid is tolerable, safe and effective to treat bone and joint infections. Tedizolid is a new FDA-approved antibiotic, and can be given through the bloodstream via an IV or orally in the form of a pill. Tedizolid has less side effects compared to linezolid and is effective against types of bacteria like S. aureus. Other research also suggests that the side effects associated with long-term therapy of older types of antibiotics may not be found with tedizolid.
This study will advance scientific knowledge of antibiotic treatments for bone and joint infections. Given the large and increasing burden of disease of bone and joint infection and the increasing acceptability of oral antibiotics for its management, tedizolid holds promise as a good option for patients with bone and joint infection. Harbor-UCLA Medical Center is a large medical center in the County of Los Angeles, the most populous County in the United States. The Infectious Disease consult service sees many bone and joint infections. Use of prolonged antibiotics is common in this setting. The investigators believe tedizolid addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for bone and joint infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug: 200mg oral Tedizolid | Experimental | 200mg oral tablet of tedizolid to be taken once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tedizolid | Drug | 200mg oral tedizolid one pill per day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Tolerability was measured by interview. We asked participants weekly about new symptoms that could suggest new onset of peripheral or optic neuropathy. | 4-12 Weeks |
| Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Safety, was measured by weekly complete blood counts (CBC), and comprehensive metabolic panels (CMP) were performed. | 4-12 Weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Outcome of "Cure" as Defined as no Need for Further Antibiotics Beyond the Originally Planned Duration Determined by the Participant's Primary/Treating Physician. | Study Hypothesis: Tedizolid is effective for the treatment of bone and joint infection. Specifically, cure will be defined as no need for further antibiotics beyond the originally planned duration (i.e., 6 weeks for non-device associated bone and joint infection or until hardware removal for subjects with implants). Unplanned surgical procedures prompted by inadequate infection control will be categorized as treatment failure. We will also measure long-term cure by performing a phone survey 3 months after completion of antibiotics. Recurrence of signs or symptoms of bone and joint infection will be considered not a long-term treatment cure (i.e., failure). |
Inclusion Criteria:
Exclusion Criteria:
Planned prolonged hospitalization (> 1 week).
Pregnancy (all female subjects of childbearing age will be given a pregnancy test prior to enrollment) or breast feeding. If a women is of childbearing potential, she must consistently use an acceptable method of contraception (IUD, injectable contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception as defined above from baseline through the course of antibiotics (4-12 weeks).
Comorbidities that, in the opinion of the investigator, are uncontrolled (e.g., diabetes, hypertension, psychiatric disease).
Peripheral or optic neuropathy.
Underlying hematologic cytopenias (e.g., baseline thrombocytopenia, or severe anemia, or leukopenia) as determined by the following limits from a baseline CBC/CMP obtained within the past 14 days. Note that if a CBC has not been performed within the past 14 days, a CBC will be performed on the day of enrollment prior to any study drug being administered to ensure the patient does not meet exclusion criteria. Cytopenias are defined as:
Severe hepatic dysfunction as defined by liver function tests (ALT, ALP, AST, total bilirubin) > 3.0 times the upper limit of normal. as determined by the following limits from a baseline CMP obtained within the past 7 days. If a CMP has not been performed within the past 7 days, baseline levels may be used from a CMP performed within the past 2 months as long as another CMP is performed on the day of enrollment and the subject's levels are within the following limits.
Hypersensitivity to tedizolid or other oxazolidinone-class antibiotics or similar compounds.
Ongoing antibiotic-associated colitis.
A diet high in tyramine-containing foods such as pickled or fermented meats and cheeses, wine, or avocados per investigator discretion.
Concurrent use of sodium picosulfate (brand names: Sodipic Picofast, Laxoberal, Laxoberon, Purg-Odan, Picolax, Guttalax, Namilax, Pico-Salax and Prepopik).
Previous participation in the study.
Use of tedizolid for any condition in the past 3 months.
Any other medical, psychological, or social condition that, in the opinion of the Investigator, would prevent the patient from fully participating in the study or would represent a concern for study compliance or constitute a safety concern to the patient.
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| Name | Affiliation | Role |
|---|---|---|
| Loren G Miller, MD MPH | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harbor-UCLA Medical Center | Torrance | California | 90502 | United States | ||
| Los Angeles BioMedical Research Institute (LA BioMed) |
After publication of trial results, data will be shared with investigators upon request to the Principal Investigator and after signing a Data Use Agreement.
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| ID | Title | Description |
|---|---|---|
| FG000 | Drug: 200mg Oral Tedizolid | 200mg oral tablet of tedizolid to be taken once daily Tedizolid: 200mg oral tedizolid one pill per day |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not different from assignment in participant flow
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| ID | Title | Description |
|---|---|---|
| BG000 | Drug: 200mg Oral Tedizolid | 200mg oral tablet of tedizolid to be taken once daily Tedizolid: 200mg oral tedizolid one pill per day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Tolerability was measured by interview. We asked participants weekly about new symptoms that could suggest new onset of peripheral or optic neuropathy. | Posted | Number | participants | 4-12 Weeks |
|
|
16 weeks to 24 weeks
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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 | Drug: 200mg Oral Tedizolid | 200mg oral tablet of tedizolid to be taken once daily Tedizolid: 200mg oral tedizolid one pill per day |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment | Self-limited non-life threatening maculopapular rash |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Loren G. Miller | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | 310-222-5623 | lgmiller@ucla.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 11, 2018 | Feb 24, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010019 | Osteomyelitis |
| ID | Term |
|---|---|
| D001850 | Bone Diseases, Infectious |
| D007239 | Infections |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C546016 | tedizolid |
| C515040 | tedizolid phosphate |
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| 16-24 Weeks |
| Torrance |
| California |
| 90502 |
| United States |
| years |
|
| Age, Customized | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Type of Bone or Joint Infection | Number | participants |
|
|
| Primary | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Safety, was measured by weekly complete blood counts (CBC), and comprehensive metabolic panels (CMP) were performed. | Posted | Number | participants | 4-12 Weeks |
|
|
|
| Other Pre-specified | Number of Participants With an Outcome of "Cure" as Defined as no Need for Further Antibiotics Beyond the Originally Planned Duration Determined by the Participant's Primary/Treating Physician. | Study Hypothesis: Tedizolid is effective for the treatment of bone and joint infection. Specifically, cure will be defined as no need for further antibiotics beyond the originally planned duration (i.e., 6 weeks for non-device associated bone and joint infection or until hardware removal for subjects with implants). Unplanned surgical procedures prompted by inadequate infection control will be categorized as treatment failure. We will also measure long-term cure by performing a phone survey 3 months after completion of antibiotics. Recurrence of signs or symptoms of bone and joint infection will be considered not a long-term treatment cure (i.e., failure). | Posted | Number | participants | 16-24 Weeks |
|
|
|
| 0 |
| 44 |
| 0 |
| 44 |
| 2 |
| 44 |
|
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| Low plateltes |
|
| High AST |
|
| High ALT |
|
| High ALP |
|