Efficacy and Safety of Stimulan® for the Treatment of Diabetic Foot Osteomyelitis. The BIG D-FOOT Study

Not Applicable

Not yet recruiting

• Conditions: Osteomyelitis - Foot; Diabete Mellitus; Foot Ulcer; Surgical Procedure, Unspecified
• Interventions: Device: Calcium-sulphate granules with tobramicina+vancomicina

• Registration Number: NCT06262854
• Lead Sponsor: Azienda Ospedaliero-Universitaria Careggi

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.

Study Timeline

• Study First Submitted: 2024-01-30
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-15
• Last Update Submitted: 2024-02-15
• Study First Posted: 2024-02-16
• Last Update Posted: 2024-02-16
• Study Start: 2024-03-01
• Primary Completion: 2025-03-01
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

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

Exclusion Criteria

• Pregnancy
• Severe cognitive impairment
• Creatinine clearance< 30 ml/min

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Calcium-sulphate granules with tobramicina+vancomicina	Calcium-sulphate granules with tobramicina+vancomicina	-
Calcium-sulphate granules without antibioitcs	Calcium-sulphate granules with tobramicina+vancomicina	-

Primary Outcome Measures

Name	Time	Method
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.	3 months	Post-surgical infective complications

Secondary Outcome Measures

Name	Time	Method
Proportion of healed patients	3 months	Complete rehepitelization of the ulcer
Proportion of post-surgical tissue infection	3 months	Tissue infection at the surgical wound level
Any non serious adverse events	3 months	Mild-moderate adverse events
Proportion of patients undergoing major amputation	3 months	Above ankle amputation
Osteomyelitis time-to-recurrence	3 months	From baseline to osteomyelitis recurrence (days)
Proportion of post-surgical dehiscence	7 days	Post-surgical infection
Proportion of osteomyelitis recurrence	3 months	Recurrence of osteomyelitis in the same foot site
Proportion of wound recurrence	3 months	New ulcer at the same site
Ulcer time-to-healing	3 months	From baseline to healing (days)
Direct medical costs	3 months	Costs for foot-related problems (hospital admission, amputation, revascularization, antibiotic therapy, medical device, etc.)
Proportion of patients undergoing new surgical intervention	3 months	New surgical intervention for osteomyelitis
Any serious adverse events	3 months	Life-threatening adverse events