Clinical trial NCT06262854: Efficacy and Safety of Stimulan® for the Treatment of Diabetic Foot Osteomyelitis. The BIG D-FOOT Study
Official title: Efficacy and Safety of aBIo- Absorbable Antibiotic Delivery in Calcium Sulphate Granules (Stimulan®) for the Treatment of Osteomyelitis in Patients With Diabetic FOOT: a Randomised, Double Blind, Controlled Clinical Study. The BIG D-FOOT Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Diabete Mellitus
Foot Ulcer
Osteomyelitis - Foot
Surgical Procedure, Unspecified
Keywords: diabetes;
foot osteomyelitis;
ulcer;
calcium sulphate local antibiotic delivery;
Stimulan
Lead sponsor: Azienda Ospedaliero-Universitaria Careggi
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed as a double-blind, placebo-controlled, parallel series randomized trial aimed at verifying the effiicacy and safety of a local calcium-sulphate bio-absorbable antibiotic delivery (tobramicina+vancomicina) versus placebo (calcium-sulphate matrix without antibiotics) in patients with diabetic foot osteomyelitis treated with surgical procedures.

Detailed description: Osteomyelitis is a severe complication of diabetic foot ulcers, that can occur in nearly 20-60% of patients. Current treatments for diabetic foot osteomyelitis (DFO) include surgical procedures aimed at removing necrotic soft tissue, gengrene and infected bones and systemic antibiotic therapy for at least 4-6 weeks; however in some cases, prolonged antibiotic therapy is not unusual.

Antibiotic therapy can be problematic for several reasons, such as the achievement of appropriate and stable therapeutic concentration at bone level, particularly due to the common presence of concomitant peripheral artery disease, and kidney impairment. In recent years, another important barrier to the treatment of DFO was the increasing incidence of resistant pathogens. On the other hand, surgical options are affected by several side effects, such as alterations of foot biomechanics possibly leading to new ulcers (the so called transfer ulcer), post-surgical infections, ecc. All these factors make the DFO treatment challenging, with a high risk of all-cause mortality and rate of patients requiring major amputations Local bio-absorbable antibiotic delivery can be a valid therapeutic option for DFO treatment. During the last 2 decades, biodegradable carriers have been developed: proteins (collagen, gelatin, thrombin etc.), synthetic polymers, grafts, and substitutes (calcium sulfate or phosphate).

Local antibiotic delivery system has been widely explored to increase the duration of local antibiotic delivery and bone penetration, achieving very high local therapeutical doses (about several times higher than that obtained with systemic antibiotic therapy) with reduced systemic toxicity. Another important advantage of this device is the possibility of using very effective, but highly toxic, antibiotic such as aminoglycosides, often not taken into account for systemic therapies.

Finally, this device can be used as a bone substitute filling the dead space caused by bone resection, thus reducing the incidence of reinfection. Complications of calcium sulfate are negligible and include postoperative drainage and transient hypercalcemia.

There several observational studies and very few randomized trials performed on DFO exploring the efficacy of local bio-absorbable antibiotic delivery and none on Stimulan.

The present study is designed as a double-blind, placebo-controlled, parallel series randomized trial aimed at verifying the effiicacy and safety of a local calcium-sulphate bio-absorbable antibiotic delivery (either with tobramicina or vancomicina) versus placebo (calcium-sulphate matrix without antibiotics) in patients with DFO treated with surgical procedures.

Eligibility criteria: Inclusion Criteria:

* Type 1 or 2 diabetes
* Forefoot osteomyelitis
* Deep tissue infection

Exclusion Criteria:

* Pregnancy
* Severe cognitive impairment
* Creatinine clearance\< 30 ml/min

Primary outcomes:
measure: The composite primary endpoint of this study will be the incidence osteomyelitis recurrence or new osteomyelitis in adjacent sites or tissue infection at the site of osteomyelitis.
timeFrame: 3 months
Secondary outcomes:
measure: Proportion of healed patients
timeFrame: 3 months
measure: Proportion of osteomyelitis recurrence
timeFrame: 3 months
measure: Proportion of post-surgical tissue infection
timeFrame: 3 months
measure: Proportion of wound recurrence
timeFrame: 3 months
measure: Proportion of patients undergoing major amputation
timeFrame: 3 months
measure: Proportion of patients undergoing new surgical intervention
timeFrame: 3 months
measure: Ulcer time-to-healing
timeFrame: 3 months
measure: Osteomyelitis time-to-recurrence
timeFrame: 3 months
measure: Any serious adverse events
timeFrame: 3 months
measure: Any non serious adverse events
timeFrame: 3 months
measure: Proportion of post-surgical dehiscence
timeFrame: 7 days
measure: Direct medical costs
timeFrame: 3 months
Other outcomes:
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