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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Foot Ulcer; Diabete Mellitus; Surgical Procedure, Unspecified; Osteomyelitis - Foot
• Intervention / Treatment: Device: Calcium-sulphate granules with tobramicina+vancomicina

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matteo Monami, PhD; Phone Number: 00393384027484; Email: matteo.monami@unifi.it
• Study Contact Backup: Name: Benedetta Ragghianti, MD; Phone Number: 0039055794332; Email: b.ragghianti@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcium-sulphate granules with tobramicina+vancomicina	Device: Calcium-sulphate granules with tobramicina+vancomicina; Local calcium-sulphate antibiotics deliver for the treatment of diabetic foot osteomyelitis
Sham Comparator: Calcium-sulphate granules without antibioitcs	Device: Calcium-sulphate granules with tobramicina+vancomicina; Local calcium-sulphate antibiotics deliver for the treatment of diabetic foot osteomyelitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Post-surgical infective complications	3 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: diabetes;; Stimulan; foot osteomyelitis;; ulcer;; calcium sulphate local antibiotic delivery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Infections; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetic Neuropathies; Foot Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Infectious; Diabetes Mellitus; Diabetic Foot; Foot Ulcer; Osteomyelitis; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: AOU Careggi Firenze

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes