Table 2 Trial registration data set

Primary registry and trial identifying number

Netherlands Trial Register NL 7582

Date of registration in primary registry

2019-03-05

Secondary identifying numbers

Dutch Diabetes Research Foundation (Diabetes Fonds) number 2017.82.014

Source(s) of monetary or material support

Dutch Diabetes Research Foundation

Primary sponsor

Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands

Address:

De Boelelaan 1117,

1081 HV, Amsterdam

+31 20 4444444

Secondary sponsor(s)

Contact for public queries

Meryl Gramberg, m.gramberg@amsterdamumc.nl

Edgar Peters, e.peters@amsterdamumc.nl

Contact for scientific queries

Meryl Gramberg, m.gramberg@amsterdamumc.nl

Edgar Peters, e.peters@amsterdamumc.nl

Public title

Using a BonE BiOPsy to Determine the Causative Agent in Persons with Diabetes and Foot Osteomyelitis (BeBoP).

Scientific title

Using a BonE BiOPsy to Determine the Causative Agent in Persons with Diabetes and Foot Osteomyelitis (BeBoP): Study Protocol for a Multicentre, Randomised Controlled Trial.

Countries of recruitment

The Netherlands

Health condition(s) or problem(s) studied

Foot osteomyelitis in persons with diabetes, bone biopsy, ulcer bed biopsy

Intervention(s)

Culture-directed antibacterial therapy based on percutaneous bone biopsy culture results (intervention group)

Culture-directed antibacterial therapy based on ulcer bed biopsy culture results (comparison group)

Key inclusion and exclusion criteria

Sexes eligible for study: all; Accepts healthy volunteers: no

Eligibility criteria are:

• ≥ 18 years

• Being able to give informed consent and willing to comply with the research protocol

• Type 1 or type 2 DM

• Moderate or severe foot infection extending to the anatomical plane of fascia, muscle, tendon or bone (International Working Group on the Diabetic Foot (IWGDF) infection grade 3 or 4 with osteomyelitis) [8].

• Subjects will have at least one of the following signs of osteomyelitis: a positive probe to bone test [8], abnormalities on plain X-ray suggestive for osteomyelitis [14], erythrocyte sedimentation rate (ESR) ≥70 mm/h (without another explanation for the elevated ESR), signs of osteomyelitis on MRI and/or FDG-PET/CT- scan [14], or positive microbiological, molecular culture results, or histology of a recent percutaneous bone biopsy performed before inclusion.

Exclusion criteria:

1. Likely to undergo complete surgical bone debridement or amputation. Subjects that (are likely to) undergo surgery within 72 h after enrolment for other reasons, e.g. abscesses, compartment syndrome, partial bone resection, are not excluded.

2. Presence of critical limb ischemia which cannot be corrected. Subjects that (are likely to) undergo surgical or percutaneous revascularisation are not excluded.

3. Severely immunocompromised (as judged by the treating physician, e.g. neutropenia due to chemotherapy, HIV infection with CD4-count of < 200/μl)

4. Pregnant or lactating

5. Unable to give informed consent

6. Unlikely to live at least 1 year

7. Unable or unwilling to follow protocol requirements (with exception of rectal swabs)

8. Received systemic antimicrobial therapy within 1 week before enrolment

Study type

Interventional

Allocation: randomised intervention model. Physician, researcher and subjects are blinded for the culture results of the not-assigned treatment strategy.

Primary purpose: diagnostic trial

Date of first enrolment

February 2019

Target sample size

80

Recruitment status

Recruiting

Primary outcome(s)

Remission of osteomyelitis at 12 months, whereby remission of osteomyelitis is defined as: an epithelialised ulcer for 28 consecutive days and absence of local inflammation and/ or stabilisation or improvement of radiologic abnormalities.

Key secondary outcomes

Time to remission, signs of inflammation or ulceration at the primary location of infection at 6 and 12 months, microbiological and molecular profiles of culture outcomes, occurrence of any surgical amputation of the primary affected leg, total antibacterial DFO therapy duration, infection-free survival days, quality of life, survival and adverse events at 12 months.