SAVE- Oral Antibiotics for Treatment of Vertebral Osteomyelitis

Recruiting

• Conditions: Osteomyelitis; Vertebra
• Interventions: Other: Early shift til oral antibiotic treatment for osteomyelitis

• Registration Number: NCT06250023
• Lead Sponsor: Rigshospitalet, Denmark

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-29
• Study First Submitted QC: 2024-01-31
• Study Start: 2024-02-01
• Study First Posted: 2024-02-08
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-22
• Primary Completion: 2026-04
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 530

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 -

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Early shift	Early shift til oral antibiotic treatment for osteomyelitis	Early shift to oral ABs (intervention) * Uncomplicated PVO: 1 week IV ABs followed by 5 weeks of oral ABs. * Complicated PVO: 1 week IV ABs followed by 11 weeks of oral ABs.

Primary Outcome Measures

Name	Time	Method
Primary outcome	Six months after completion of oral antibiotic treatment	Renewed course of intravenous antibiotic given for more than 7 days for treatment of pyogenic vertebral osteomyelitis

Secondary Outcome Measures

Name	Time	Method
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 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 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 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 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
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.

Trial Locations

Locations (1)

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark; 🇩🇰 Copenhagen, Denmark