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Bedside Bone Biopsy in Diabetic Foot Osteomyelitis (BOLBOC)

Primary Purpose

Subjects With Diabetes and DFU With a Suspicion of DFO

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Bedside blind bone biopsy procedure
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Subjects With Diabetes and DFU With a Suspicion of DFO focused on measuring Bedside bone biopsy, conventional bone biopsy, diabetes, Diabetic Foot Ulcer (DFU), diabetic foot osteomyelitis (DFO)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 Diabetic charcot foot 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

Sites / Locations

  • Bichat - Claude Bernard Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bedside blind bone biopsy procedure

Standard bone biopsy procedure

Arm Description

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

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

Outcomes

Primary Outcome Measures

the remission of DFO
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 Outcome Measures

Clinical efficacy
Remission of DFO at 6 months
Clinical efficacy
Need for surgery for initial DFU during follow-up
Clinical efficacy
Recurrence of DFU during follow-up
Clinical efficacy
Death during follow-up
Clinical efficacy
Number of hospitalizations
Clinical efficacy
length of hospitalizations
Clinical efficacy
Length of stay of the initial hospitalization (in days)
Microbiological results
Number of microorganisms per biopsy
Microbiological results
Number of resistant microorganisms per biopsy
Microbiological results
Total duration of the antibacterial therapy (mean in days)
Occurrence of adverse events during the study
Remission rate of DFO
Remission rate of DFO at 12 months according to microbiological results of BB (positive or negative)
costs: Average costs of the biopsies
costs: Average total 1-year costs
Average 1 year QALY
Incremental cost effectiveness ratio
defined as the difference in average total costs/ average total QALY

Full Information

First Posted
September 27, 2023
Last Updated
September 28, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT06066801
Brief Title
Bedside Bone Biopsy in Diabetic Foot Osteomyelitis
Acronym
BOLBOC
Official Title
Bedside Bone Biopsy Versus Conventional Bone Biopsy for Management of Diabetic Foot Osteomyelitis: an Open-label Controlled Randomized Non-inferiority Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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) The health economic of this study are to: to estimate total costs for the intervention and total medical costs in each groups to estimate total quality adjusted life years (QALYs) based upon EQ5D5L scores to calculate the point estimate of the incremental cost utility ratio and estimate the probability of decremental cost effectiveness for the beside blind bone biopsy compared to conventional biopsy. In this study, we will include subjects with diabetes and DFU with a suspicion of DFO. DFO is a complication of a large amount of DFU and is a major trigger of lower limb amputations. As we will include participants before bacteriological confirmation of DFO through bone biopsy, we will use the clinical and radiological criteria for DFO according to IWGDF 2019 guidelines4. These criteria include having at least one of the following signs: 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 18Fluor-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT- scan

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subjects With Diabetes and DFU With a Suspicion of DFO
Keywords
Bedside bone biopsy, conventional bone biopsy, diabetes, Diabetic Foot Ulcer (DFU), diabetic foot osteomyelitis (DFO)

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bedside blind bone biopsy procedure
Arm Type
Experimental
Arm Description
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
Arm Title
Standard bone biopsy procedure
Arm Type
Active Comparator
Arm Description
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 Type
Procedure
Intervention Name(s)
Bedside blind bone biopsy procedure
Intervention Description
It was performed in the patient's room under aseptic conditions. Pain relievers were given orally within the hour preceding the procedure. Superficial anesthesia was performed firstly subcutaneously and then on the periosteum, Inhaled anesthesia was started concomitantly. Following a short incision with a scalpel, the trocar inside a cannula was inserted through healthy skin at a minimum distance of 2 cm from the ulcer edge, close to the bone, preferentially on dorsal foot side. When the trocar was firmly inserted into the bone, it was pulled out from the cannula. Biopsy needle was then slipped into the cannula and twisted into the bone clockwise. Biopsy needle was then pulled out and the bone was pushed out with the ejector pin into a sterile surgical drape and divided in two parts.
Primary Outcome Measure Information:
Title
the remission of DFO
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Clinical efficacy
Description
Remission of DFO at 6 months
Time Frame
12 months
Title
Clinical efficacy
Description
Need for surgery for initial DFU during follow-up
Time Frame
12 months
Title
Clinical efficacy
Description
Recurrence of DFU during follow-up
Time Frame
12 months
Title
Clinical efficacy
Description
Death during follow-up
Time Frame
12 months
Title
Clinical efficacy
Description
Number of hospitalizations
Time Frame
12 months
Title
Clinical efficacy
Description
length of hospitalizations
Time Frame
12 months
Title
Clinical efficacy
Description
Length of stay of the initial hospitalization (in days)
Time Frame
12 months
Title
Microbiological results
Description
Number of microorganisms per biopsy
Time Frame
12 months
Title
Microbiological results
Description
Number of resistant microorganisms per biopsy
Time Frame
12 months
Title
Microbiological results
Description
Total duration of the antibacterial therapy (mean in days)
Time Frame
12 months
Title
Occurrence of adverse events during the study
Time Frame
12 months
Title
Remission rate of DFO
Description
Remission rate of DFO at 12 months according to microbiological results of BB (positive or negative)
Time Frame
12 months
Title
costs: Average costs of the biopsies
Time Frame
1 month
Title
costs: Average total 1-year costs
Time Frame
12 months
Title
Average 1 year QALY
Time Frame
12 months
Title
Incremental cost effectiveness ratio
Description
defined as the difference in average total costs/ average total QALY
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 Diabetic charcot foot 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Louis Potier, MD, PhD
Phone
01 40 25 88 03
Email
louis.potier@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis Potier, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bichat - Claude Bernard Hospital
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Louis Potier, MD, PhD
Phone
01 40 25 88 03
Email
louis.potier@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Bedside Bone Biopsy in Diabetic Foot Osteomyelitis

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