Bedside Bone Biopsy Versus Conventional Bone Biopsy for Management of Diabetic Foot Osteomyelitis: an Open-label Controlled Randomized Non-inferiority Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 320
- Locations
- 1
- Primary Endpoint
- the remission of DFO
Study Overview
Brief Summary
During their lifetime, 15 to 25% of patients with diabetes mellitus will develop a Diabetic Foot Ulcer (DFU) related to neuropathy and/or peripheral arterial disease. DFU is the leading cause of non-traumatic lower-extremity amputation worldwide. Diabetic foot osteomyelitis (DFO), which complicates up to 60% of DFU, is a major trigger of amputation in over 80% of persons with diabetes resulting in subsequent loss of quality of life. It has been shown that medical treatment of DFO may prevent amputations with early diagnosis of osteomyelitis and appropriate use of antibiotics. Empirical antimicrobial treatment is not recommended for DFO as for other chronic infections. Surgically or radiologically acquired bone sample for culture is the reference standard recommended by the International Working Group of Diabetic Foot (IWGDF) to diagnose DFO and to determine the causative bacteria and their susceptibility. However, defining appropriate antimicrobial therapy directed to the causative bacteria in DFO is challenging since it requires bone biopsy (BB) procedures which are underused in clinical practice for various reasons: lack of availability, cost, and delay. Some clinicians also find bone biopsy cumbersome or too invasive.
To overcome these barriers, we have set up for a few years a bedside blind BB procedure performed by diabetologists at the bedside in the clinical ward. Since then, this method has been used in more than 200 patients with DFO in the diabetology departments of Lariboisiere Hospital and Bichat Hospital (Paris). We have recently published our observational data of 79 patients showing that bedside BB is a simple, safe and efficient procedure for the diagnosis of DFO with a similar rate of complete healing at 12 months compared to conventional surgical or radiological bone biopsies. In order to extend and confirm these preliminary and observational results, the aim of this study is to compare the efficiency and safety of bedside BB versus conventional bone biopsy in a randomized controlled trial (RCT) of patients with DFO. Our hypothesis is that bedside BB is non-inferior to conventional bone biopsy in DFO and can be used as a simpler alternative procedure to document DFO
Detailed Description
During their lifetime, 15 to 25% of patients with diabetes mellitus will develop a Diabetic Foot Ulcer (DFU) related to neuropathy and/or peripheral arterial disease1. DFU is the leading cause of non-traumatic lower-extremity amputation worldwide. DFO, which complicates up to 60% of DFU, is a major trigger of amputation in over 80% of persons with diabetes resulting in subsequent loss of quality of life2. It has been shown that medical treatment of DFO may prevent amputations with early diagnosis of osteomyelitis and appropriate use of antibiotics3. Empirical antimicrobial treatment is not recommended for DFO as for other chronic infections. Surgically or radiologically acquired bone sample for culture is the reference standard recommended by the International Working Group of Diabetic Foot (IWGDF) to diagnose DFO and to determine the causative bacteria and their susceptibility4. However, defining appropriate antimicrobial therapy directed to the causative bacteria in DFO is challenging since it requires bone biopsy (BB) procedures which are underused in clinical practice for various reasons including lack of availability, cost, and delay. Some clinicians also find bone biopsy cumbersome or too invasive.
To overcome these barriers, we have set up for a few years a bedside blind BB procedure performed by a physician at the bedside in the clinical ward. Since then, this method has been used in more than 200 patients with DFO in the diabetology departments of Lariboisiere Hospital and Bichat Hospital (Paris). We have recently published our observational data of 79 patients showing that bedside BB is a simple, safe and efficient procedure for the diagnosis of DFO with a similar rate of complete DFU healing at 12 months compared to conventional surgical or radiological bone biopsies6. In order to extend and confirm these preliminary and observational results, the aim of this study is to compare the efficiency and safety of bedside versus conventional BB in a randomized controlled trial (RCT) of patients with DFO. Our hypothesis is that bedside BB is non inferior to conventional BB in DFO outcomes and can be used as a simpler alternative procedure to document DFO.
The main objective is to demonstrate non-inferiority of beside blind bone biopsy compared to conventional bone biopsy (surgical or radiological) on DFO remission without surgery at 1 year.
The secondary objectives of this study are to:
- compare clinical efficacy between groups of bone biopsy
- compare microbiological culture results between groups
- compare the safety of both procedures
- compare DFO remission according to results of BB (negative or positive)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients eligible for inclusion in this study must fulfill all of the following criteria:
- •Aged >18 years
- •Diabetes mellitus
- •At least one of the following signs of osteomyelitis according to IWGDF 2019 guidelines:
- •A positive probe to bone test and abnormalities on plain X-ray suggestive for osteomyelitis Signs of osteomyelitis on CT-scan and/or MRI and/or white blood cell SPECT/CT and/or FDG-PET/CT-scan
- •- Absence of antibacterial therapy within 14 days before inclusion
Exclusion Criteria
- •Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
- •Urgent need for surgery
- •Critical limb ischemia which cannot be corrected by revascularization procedure
- •Subjects that (are likely to) undergo surgical or percutaneous revascularization are not excluded
- •Antibiotic treatment in the last 15 days before bone biopsy
- •Osteomyelitis in the area of the Charcot foot destructive process
- •Unlikely to live at least 1 year
- •Not being able to give informed consent and willing to comply with the research protocol
- •Pregnant or breastfeeding women
- •Absence of affiliation to French social insurance
- •State medical aid (AME)
- •Deprivation of liberty, being under a legal protective measure
Arms & Interventions
Bedside blind bone biopsy procedure
Bedside blind bone biopsy procedure performed by a physician of the participating center through healthy skin with bone trocar following local and light systemic anesthesia. Samples will be analyzed for microbiology and histopathology
Intervention: Bedside blind bone biopsy procedure (Procedure)
Standard bone biopsy procedure
Standard BB procedure (surgical or radiological) performed according to the local standard of care of each participating center and done through healthy skin and under locoregional anesthesia. Samples will be analyzed for microbiology and histopathology
Intervention: Bedside blind bone biopsy procedure (Procedure)
Outcomes
Primary Outcomes
the remission of DFO
Time Frame: 12 months
The remission of DFO at 12 months and is defined by a composite criterion as: * an epithelialized ulcer for 28 consecutive days * and absence of local inflammation and/or stabilization or improvement of radiologic abnormalities * and no need for surgery of the foot to treat DFO during follow-up
Secondary Outcomes
- Microbiological results(12 months)
- Clinical efficacy(12 months)
- Remission rate of DFO(12 months)
- costs: Average costs of the biopsies(1 month)
- Occurrence of adverse events during the study(12 months)
- Average 1 year QALY(12 months)
- costs: Average total 1-year costs(12 months)
- Incremental cost effectiveness ratio(12 months)