Bone and Joint Infection
Conditions
Keywords
bone and joint infection, osteomyelitis, tedizolid
Brief summary
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.
Detailed description
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.
Interventions
DRUGTedizolid
200mg oral tedizolid one pill per day
Sponsors
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Treatment of bone and joint infection in which therapy for Gram positive organisms is documented or suspected, as determined by the treating physician and treatment of at least 4 weeks is planned. Bone and joint infection and trauma-associated bone and joint infection will defined clinically using radiologic (e.g., MRI) and/or surgical (e.g., intra-operative findings) definitions. All subjects must have confirmation (diagnosis mentioned in chart) by the patient's primary physician and consultants that the patients has or likely has bone and joint infection and requires prolonged antibiotic therapy. * Aged between 18 years and 85 years. * Plans to treat bone and joint infection in outpatient setting. * No limited planned course of antibiotics (i.e., no indefinite treatment plans for chronic suppression). Co-administration of other antibiotics that target other causative or potentially causative organisms (e.g., fluoroquinolones) is acceptable. * Able to come to the research clinic for study follow-up visits for the study period.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | 4-12 Weeks | Safety, was measured by weekly complete blood counts (CBC), and comprehensive metabolic panels (CMP) were performed. |
| Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | 4-12 Weeks | Tolerability was measured by interview. We asked participants weekly about new symptoms that could suggest new onset of peripheral or optic neuropathy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. | 16-24 Weeks | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug: 200mg Oral Tedizolid 200mg oral tablet of tedizolid to be taken once daily
Tedizolid: 200mg oral tedizolid one pill per day | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Drug: 200mg Oral Tedizolid |
|---|---|
| Age, Continuous | 46 years |
| Age, Customized Mean | 44 years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Black/African American | 10 Participants |
| Race/Ethnicity, Customized Decline to State | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 23 Participants |
| Race/Ethnicity, Customized Native American/Native Indian | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 35 Participants |
| Type of Bone or Joint Infection External-fixator associated | 1 participants |
| Type of Bone or Joint Infection Hardware-associated infection | 17 participants |
| Type of Bone or Joint Infection Osteomyelitis, non-hardware associated | 13 participants |
| Type of Bone or Joint Infection Prosthetic joint infection | 5 participants |
| Type of Bone or Joint Infection Septic arthritis | 1 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 44 |
| other Total, other adverse events | 2 / 44 |
| serious Total, serious adverse events | 0 / 44 |
Outcome results
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.
Time frame: 4-12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | High ALP | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | High leukocytes | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Low leukocytes | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Low hemoglobin | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Low plateltes | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | High AST | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | High ALT | 0 participants |
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.
Time frame: 4-12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drug: 200mg Oral Tedizolid | Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Reported peripheral neuropathy | 0 participants |
| Drug: 200mg Oral Tedizolid | Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated | Reported optic neuropathy | 0 participants |
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).
Time frame: 16-24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug: 200mg Oral Tedizolid | 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. | 13 participants |