Clinical trial NCT03009045: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections (OTTER)
Official title: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bone and Joint Infection
Keywords: bone and joint infection
osteomyelitis
tedizolid
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
First posted: 2017-01-04
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria. Cytopenias are defined as:

  1. Hemoglobin (Hgb) \< 8.0g/dL
  2. WBC \< 4,000 k/cumm
  3. Platelets \< 150,000 k/cumm
* 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.

Primary outcomes:
measure: Quantify the Tolerability of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated
timeFrame: 4-12 Weeks
measure: Quantify the Safety of Tedizolid for Bone and Joint Infections, Both Hardware and Non-hardware Associated
timeFrame: 4-12 Weeks
Secondary outcomes:
Other outcomes:
measure: 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.
timeFrame: 16-24 Weeks
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Torrance
country: United States
facility: Los Angeles BioMedical Research Institute (LA BioMed)
state: California
Study officials:
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: Loren G Miller, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: