Conservative Versus Surgical Treatment of Native Vertebral Osteomyelitis

NCT04436328 | Unknown

• 1 other identifier: Spine infection treatment
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The optimal treatment of uncomplicated native vertebral osteomyelitis (NVO) is unknown. While some authors recommend surgical treatment (consisting of spinal debridement, decompression and instrumentation using hardware implantation of hardware), others recommend conservative treatment (with antimicrobial therapy alone). In the proposed randomized controlled multicentric trial, we plan to compare the outcome of conservative vs, surgical treatment of NVO regarding (i) infection outcome (i.e. infection-free proportion of subjects), (ii) functional outcome (pain intensity, spine scores, general mobility, quality of life evaluation), and (iii) socioeconomic impact (direct and indirect costs due to NVO). A total of 350 subjects will be screened, 300 subjects will be randomized 1:1 into 2 arms: experimental (surgical treatment) and control (conservative treatment). Subjects in both groups will receive pathogen-directed antimicrobial therapy for 6 weeks. Excluded will be patients with acute neurologic impairment, extensive bone destruction, epidural/intraspinal abscess and with spinal hardware. The clinical impact of this study is enormous since it will generate evidence for rational treatment guidelines. We hypothesize that the conservative treatment of uncomplicated NVO is non-inferior to surgical therapy regarding infection outcome. If the conservative treatment of NVO demonstrate non-inferiority, patients may benefit from avoiding unnecessary surgical intervention.

Conditions

Vertebral Osteomyelitis; Spondylodiscitis; Surgical Procedure, Unspecified

Keywords

Native vertebral osteomyelitis; Treatment; Spinal implant; Antibiotic therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of infection-free subjects

  Treatment success: Infection-free status defined as (i) absence of clinical signs of native vertebral osteomyelitis (fever, local signs at surgical site), (ii) normal laboratory findings (serum C-reactive protein), (iii) absence of radiological signs of active native vertebral osteomyelitis (progressive bone destruction, implant loosening or migration), and (iv) absence of unplanned surgical interventions or additional antimicrobial treatment. Confirmed failure: Persistence or relapse of infection due to the same pathogen. Possible failure: Subjects not fulfilling the criteria for treatment success but have no diagnosis of persistence or relapse of native vertebral osteomyelitis

  12 months after treatment initiation

Secondary Outcomes (5)

• Functional outcome regarding pain intensity

  12 months after treatment initiation

• Functional outcome regarding mobility according to Nurick scale

  12 months after treatment initiation

• Functional outcome regarding mobility according Oswestry Disability Index

  12 months after treatment initiation

• Functional outcome regarding quality of life using EuroQOL score

  12 months after treatment initiation

• Functional outcome regarding quality of life using SF-36 questionnaire

  12 months after treatment initiation

Study Arms (2)

Surgical treatment

EXPERIMENTAL

Surgical treatment of native vertebral osteomyelitis followed by antimicrobial therapy

Procedure: Surgical treatment

Antimicrobial treatment

ACTIVE COMPARATOR

No surgical intervention, antimicrobial therapy only

Other: Antimicrobial treatment

Interventions

Surgical treatment PROCEDURE

Surgical treatment of native vertebral osteomyelitis consisting of debridement, spinal decompression and instrumentation using hardware. Additional standard antimicrobial therapy, according to the pathogen and its antimicrobial susceptibility (intravenous route during first 2 weeks, followed by oral route for additional 4 weeks).

Surgical treatment

Antimicrobial treatment OTHER

No surgical intervention, antimicrobial therapy only, bed rest or temporary external immobilization of affected spinal segment with orthopedic orthesis. Antimicrobial therapy will be administrated according to the pathogen type and antimicrobial susceptibility, with initial intravenous administration for 2 weeks, followed by oral antibiotics for 4 weeks to complete 6 weeks of total therapy.

Antimicrobial treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged ≥18 years with NVO, diagnosed by microbiology (positive blood culture or vertebral tissue culture) or histopathology.
• Subjects are willing to participate in the study (signed informed consent) and comply with planned follow-up assessments at 3, 6 and 12 months).

You may not qualify if:

• Infection due to Mycobacterium spp. or Brucella spp.
• Infection associated with spinal hardware
• Acute neurologic impairment
• Extensive defect of vertebral body (\>2 cm)
• Extensive epidural abscess (\>1 cm) or intraspinal abscess (any size)
• Spinal instability/deformity requiring immediate stabilisation

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Publications (7)

• Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, Hendershot EF, Holtom PD, Huddleston PM 3rd, Petermann GW, Osmon DR. Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015 Sep 15;61(6):859-63. doi: 10.1093/cid/civ633.

  PMID: 26316526 RESULT

• Bernard L, Dinh A, Ghout I, Simo D, Zeller V, Issartel B, Le Moing V, Belmatoug N, Lesprit P, Bru JP, Therby A, Bouhour D, Denes E, Debard A, Chirouze C, Fevre K, Dupon M, Aegerter P, Mulleman D; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet. 2015 Mar 7;385(9971):875-82. doi: 10.1016/S0140-6736(14)61233-2. Epub 2014 Nov 5.

  PMID: 25468170 RESULT

• Shiban E, Janssen I, Wostrack M, Krieg SM, Ringel F, Meyer B, Stoffel M. A retrospective study of 113 consecutive cases of surgically treated spondylodiscitis patients. A single-center experience. Acta Neurochir (Wien). 2014 Jun;156(6):1189-96. doi: 10.1007/s00701-014-2058-0. Epub 2014 Mar 27.

  PMID: 24671549 RESULT

• Murillo O, Grau I, Lora-Tamayo J, Gomez-Junyent J, Ribera A, Tubau F, Ariza J, Pallares R. The changing epidemiology of bacteraemic osteoarticular infections in the early 21st century. Clin Microbiol Infect. 2015 Mar;21(3):254.e1-8. doi: 10.1016/j.cmi.2014.09.007. Epub 2014 Oct 12.

  PMID: 25618436 RESULT

• Rutges JP, Kempen DH, van Dijk M, Oner FC. Outcome of conservative and surgical treatment of pyogenic spondylodiscitis: a systematic literature review. Eur Spine J. 2016 Apr;25(4):983-99. doi: 10.1007/s00586-015-4318-y. Epub 2015 Nov 19.

  PMID: 26585975 RESULT

• Valancius K, Hansen ES, Hoy K, Helmig P, Niedermann B, Bunger C. Failure modes in conservative and surgical management of infectious spondylodiscitis. Eur Spine J. 2013 Aug;22(8):1837-44. doi: 10.1007/s00586-012-2614-3. Epub 2012 Dec 18.

  PMID: 23247861 RESULT

• Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med. 2010 Mar 18;362(11):1022-9. doi: 10.1056/NEJMcp0910753. No abstract available.

  PMID: 20237348 RESULT

MeSH Terms

Conditions

Discitis

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Spondylitis; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of septic surgery

Model Details: Prospective, randomized (1:1), controlled, multicentre explorative trial

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 18, 2020
• Study Start: July 1, 2020
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2022
• Last Updated: June 18, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)