Diabete Mellitus, Foot Ulcer, Osteomyelitis - Foot, Surgical Procedure, Unspecified
Conditions
Keywords
diabetes;, foot osteomyelitis;, ulcer;, calcium sulphate local antibiotic delivery;, Stimulan
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.
Interventions
DEVICECalcium-sulphate granules with tobramicina+vancomicina
Local calcium-sulphate antibiotics deliver for the treatment of diabetic foot osteomyelitis
Sponsors
Azienda Ospedaliero-Universitaria Careggi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Granules of calcium sulphate with and without antibiotics are identical and undistinguishable.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 or 2 diabetes * Forefoot osteomyelitis * Deep tissue infection
Exclusion criteria
* Pregnancy * Severe cognitive impairment * Creatinine clearance\< 30 ml/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of wound recurrence | 3 months | New ulcer at the same site |
| Proportion of patients undergoing major amputation | 3 months | Above ankle amputation |
| Proportion of healed patients | 3 months | Complete rehepitelization of the ulcer |
| Proportion of osteomyelitis recurrence | 3 months | Recurrence of osteomyelitis in the same foot site |
| Proportion of patients undergoing new surgical intervention | 3 months | New surgical intervention for osteomyelitis |
| Proportion of post-surgical tissue infection | 3 months | Tissue infection at the surgical wound level |
| Osteomyelitis time-to-recurrence | 3 months | From baseline to osteomyelitis recurrence (days) |
| Any serious adverse events | 3 months | Life-threatening adverse events |
| Any non serious adverse events | 3 months | Mild-moderate adverse events |
| Proportion of post-surgical dehiscence | 7 days | Post-surgical infection |
| Direct medical costs | 3 months | Costs for foot-related problems (hospital admission, amputation, revascularization, antibiotic therapy, medical device, etc.) |
| Ulcer time-to-healing | 3 months | From baseline to healing (days) |
Contacts
Primary ContactMatteo Monami, PhD
Backup ContactBenedetta Ragghianti, MD
Outcome results
None listed