Osteomyelitis; Vertebra
Conditions
Brief summary
Background The current Danish National Guideline for treatment of pyogenic vertebral osteomyelitis (PVO) recommends 6 weeks antibiotic (AB) treatment, with a 2-week intravenous (IV) AB lead-in followed by 4 weeks oral AB for uncomplicated PVO, and 12 weeks AB treatment with a 2-4-week IV AB lead-in followed by 8 weeks oral AB for complicated PVO. The primary objective of the current study is to investigate whether shortening the duration of IV AB to one week for both complicated and uncomplicated PVO is non-inferior to the current Danish National Guideline.
Interventions
OTHEREarly shift til oral antibiotic treatment for osteomyelitis
To investigate whether early transition to oral AB treatment after one week of IV treatment is non-inferior to the current national guideline of continued IV AB treatment for two to four weeks followed by oral AB treatment for PVO.
Sponsors
Rigshospitalet, Denmark
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Diagnosed with PVO by a physician based on clinical symptoms and findings consistent with PVO in combination with diagnostic imaging (MRI, PET/CT or PET/MRI) 3. The physician responsible for the patient decides to treat the patient for PVO 4. At time of randomization CRP has decreased to \< 75% of peak value or to \< 20 mg/l 5. At the time of randomization patient has received maximum 7 days of appropriate IV AB for PVO -
Exclusion criteria
1. Previous episodes of PVO within the past 24 months 2. Spinal implants inserted prior to current episode of PVO 3. Hypersensitivity to an AB intended for use in the patient and no alternative drugs available. 4. Oral ABs not possible due to suspicion of reduced absorption 5. Oral Abs not possible due to verified or expected bacterial susceptibility or due to expected toxicity of available regimen 6. Identification of fungus, mold, TB, Brucella, Actinomyces, Nocardia and P. aeruginosa as etiology 7. Severe immunocompromise defined as primary immunodeficiencies, uncontrolled HIV/AIDS, organ transplant recipients, hematological malignancies, patients undergoing biological therapy or chemotherapy and patients treated with prednisolone \>=20 mg daily \>14 days 8. Verified or expected reduced compliance (for example iv drug use) 9. Pregnancy 10. Breastfeeding 11. Women of childbearing potential, who at the time of inclusion are not using and/or who will not use an effective anticonception method during the treatment period. 12. Patients not capable of providing informed consent at time of screening for inclusion 13. Diagnosed or suspected concomitant or unrelated infections necessitating IV AB therapy beyond 7 days of duration at the time of randomization -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome | Six months after completion of oral antibiotic treatment | All-cause mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcome 2 | Six months after completion of oral antibiotic treatment | Median duration of hospital admission(s) from the time of shift to oral AB treatment to six months after completion of oral AB treatment (Admission defined as overnight stay at the department) |
| Secondary outcome 3 | Six months after completion of oral antibiotic treatment | Number of readmissions from the time of shift to oral AB treatment to six months after completion of oral AB treatment |
| Secondary outcome 4 | Six months after completion of oral antibiotic treatment | Proportion of patients receiving additional oral AB therapy beyond the duration defined in the protocol |
| Secondary outcome 5 | Six months after completion of oral antibiotic treatment | Proportion of patients having early termination of allocated treatment strategy due to adverse events, patient preference, or any other reason |
| Secondary outcome 6 | Six months after completion of oral antibiotic treatment | Proportion of patients experiencing complications associated with IV treatment (e.g., catheter infections, phlebitis, bleeding, venous thrombosis, need for replacement of catheter) from the time of initiation of IV treatment for PVO to six months after completion of oral AB treatment |
| Secondary outcome 7 | Six months after completion of oral antibiotic treatment | Proportion of patients experiencing severe adverse events from ABs from the time of initiation of IV treatment for PVO to six months after completion of oral AB treatment |
| Secondary outcome 1 | Six months after completion of oral antibiotic treatment | Occurrence of each component of the composite primary endpoint from the time of shift to oral AB treatment to six months after completion of oral AB treatment. |
| Secondary outcome 9 | Six months after completion of oral antibiotic treatment | Proportion of patients diagnosed with Clostridioides difficile associated diarrhea from the time of initiation of IV treatment for PVO to six months after completion of oral AB treatment |
| Secondary outcome 10 | Six months after completion of oral antibiotic treatment | Quality of life scores (EQ-5D) at the following timepoints: Randomization, 1 week after the end of AB therapy, 1 month after the end of AB therapy, 6 months after the end of oral AB therapy, and 12 months after the end of oral AB therapy |
| Secondary outcome 11 | Six months after completion of oral antibiotic treatment | Resource allocation/cost assessment determined by a combination of EQ5D, DALYs, Days of hospital admission and antibiotic prescribing costs |
| Secondary outcome 12 | Six months after completion of oral antibiotic treatment | CRP, WBC, alkaline phosphatase and procalcitonin at randomization as well as CRP, WBC, alkaline phosphatase weekly during treatment and at week 4, 12 and 24 after completion of oral AB treatment. |
| Secondary outcome 13 | Six months after completion of oral antibiotic treatment | Presence of microbial cell-free DNA in blood samples at the time of randomization and 6 months after the end of oral AB therapy |
| Secondary outcome 8 | Six months after completion of oral antibiotic treatment | Proportion of patients experiencing adverse events from ABs from the time of initiation of IV treatment for PVO to six months after completion of oral AB treatment |
Countries
Denmark
Contacts
Primary ContactAnne-Mette Lebech, MD
Outcome results
None listed