RCT on Bioactive Glass S53P4 in Diabetic Foot Osteomyelitis in the Forefoot (DFORCT)

Not Applicable

Recruiting

• Conditions: Osteomyelitis - Foot
• Interventions: Device: Bioactive Glass; Other: Standard of Care

• Registration Number: NCT06388603
• Lead Sponsor: ASST Ovest Milanese

Brief Summary

The Study will be a prospective multicenter randomized trial, focused on the management of acute and chronic Osteomilytis in Diabetic Foot patients. The aim of this Study will be to compare the effectiveness and safety of S53P4 bioactive glass, medical device class III used as per its CE mark indication and Instruction For Use, in the surgical management of OM in the forefoot performed as per local surgical standard of care, in the same indications in a group of Diabetic Foot patients admitted in highly specialized dedicated centers.

Participants will randomized into two groups:

* Patients in Group A will be treated with surgical removal of the affected bone, debridement of infected soft tissues and systemic antibiotic therapy targeted on the sampling on the bone during the surgical procedure, with or without use of bone substitutes (with the only exception of Bioactive glasses) according to the judgement of the operator as per normal practice.

* Patients in Group B will be debrided as well and the infected bone will be debrided without eliminating completely the structure of the bone, but instead preserving the cortex, while all the soft bone visibly infected will be removed and then replaced with Bioactive glass, as per IFU, (S53P4 - Bonalive® granules and putty, Bonalive Biomaterials Ltd. Finland) and then closed for primary intention whenever possible.

Detailed Description

Patient with a diagnosis of ostemileytis localised in the forefoot will be randomized into two groups.

* Patients in Group A will be treated with surgical removal of the affected bone, debridement of infected soft tissues and systemic antibiotic therapy targeted on the sampling on the bone during the surgical procedure, with or without use of bone substitutes (with the only exception of Bioactive glasses) according to the judgement of the operator as per normal practice.

* Patients in Group B will be debrided as well and the infected bone will be debrided without eliminating completely the structure of the bone, but instead preserving the cortex, while all the soft bone visibly infected will be removed and then replaced with Bioactive glass, as per IFU, (S53P4 - Bonalive® granules and putty, Bonalive Biomaterials Ltd. Finland) and then closed for primary intention whenever possible.

In any case a primary intent closure is pursued, both in Group A and B, a vacuum percutaneous drainage would be placed before closing the wound and removed in 2nd post-operative day, if necessary, by the surgeon.

Systemic antibiotic therapy will be started immediately on empirical basis, as per normal practice.

After the removal of drainage, or after the first post-operative control in 2nd post-operative day, as done routinely at study sites, patients will be evaluated biweekly either if they are still admitted or if they were dismissed and will be followed up by investigators blinded toward the groups.

At each visit local conditions and eventual dressing changes will be recorded, alongside with any possible complication, like non-healing, re-infection, and any systemic and local adverse event.

Patients will be followed every second week up to 3 months or until complete healing and then at six months and 12 months from surgical interventions. At six-month and 12 -month follow-up, rate of healing and recurrences will be checked; x-rays will be performed at pre-operation visit, immediate post and at 12 months Follow Up visit. Histopathological samples collected as per normal practice during the surgery will be analyzed with standard protocol in local laboratories. Healing will be defined as complete re-epithelization of the lesion, without secretion or drainage, confirmed at two successive follow-up visits. For the sake of calculating healing time, healing will be attributed to the first visit. At each visits a local and systemic evaluation of the wound will be done as per normal practice. A photo of the wound will be taken at visits: Pre-operative , Immediate post-op, 6 weeks post-op, 6 months and 12 months after the surgical procedure. Laboratory exams will be performed as per hospital standard of care. At pre-operative and 6 months and 12 months visits patients compile Quality of Life and Foot Function Index Questionnaires.

Study Timeline

• Study Start: 2024-03-21
• Status Verified: 2024-04
• Study First Submitted: 2024-04-19
• Study First Submitted QC: 2024-04-24
• Last Update Submitted: 2024-04-24
• Study First Posted: 2024-04-29
• Last Update Posted: 2024-04-29
• Primary Completion: 2026-09-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Written informed consent obtained.
2. Male or female patients >= of 18 years old.
3. They should have type I since at least 5 years or type II DM
4. They should have a diagnosis - confirmed by imaging and culture - of OM localized in the forefoot not responding for at least 2 up to 6 weeks to systemic antibiotic therapy and/or associated with soft tissue infection, abscess, phlegmon, necrosis, and for which a surgical debridement is indicated.
5. They should have palpable pulses on TP or DP at the ankle in the affected limb, and/or ABPI >0.7 and <1.2 and /or TcPO2 at dorsum of the foot ≥36 mmHg.
6. They should be able to accomplish with the procedures and prescriptions indicated by the Study protocol, particularly with the offloading prescription, as well as they should be willing and able to attend and respect the program of control visits and medications.
7. Anatomical area: forefoot.

Exclusion Criteria

1. They should not have metabolic decompensation as witnessed by HbA1c >109 mmol/mol (> 12%).
2. They should not have major amputation on the contra-lateral limb.
3. They should not have acute or chronic Charcot's foot in the affected foot.
4. They should not have undergone surgical or endovascular revascularization in the affected foot in the month preceding the enrollment.
5. They should not be taking corticosteroids, bisphosphonates, immunosuppressants, and more in general any drug which might interfere with bone metabolism or tissue repair, in thejudgment of investigators.
6. They should not have ESRD in dialysis.
7. They should not be bedridden or not ambulating.
8. They should not have a life expectancy shorter than one year.
9. They should not be too ill to sustain a surgical procedure under loco-regional anesthesia.
10. They should not have severe disease which might interfere with the expected course of the disease and therapy.
11. Hypersensitivity to any product ingredient(s) or history of anaphylactic reactions.
12. Participation in another interventional studies within 45 days prior to the start of the present study.
13. Predictable poor compliance or inability to communicate well with the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bioactive Glass	Bioactive Glass	Subjects randomized in this group will be treated using the S53P4 Bioactive Glass of Bonalive Biomaterials Ltd; in the form of: * Bonalive Granules 2.5 CC (0.5-0.8 MM) * Bonalive Putty 2.5 CC (SIRINGA 0.5-0.8 MM) The quantity that will be implanted will vary according to the bone cavity of each patient.
Standard of Care - Osteomyelitis treatment	Standard of Care	Subjects randomized in this group will be treated according to standard of care for the surgical managment of Osteomyelitis in the forefoot in patient suffering from diabetic foot syndrome. All standard of care approaches will be allowed (e.g use of bone sobsitutes, cements, cements loaded with antibiotics etc) with the only exception of Bioactive Glasses.

Primary Outcome Measures

Name	Time	Method
healing rate	6-month	complete re-epithelization of the lesion, without secretion or drainage, confirmed at two successive follow-up visits.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients undergoing amputations	through study completion, an average of 1 year	In same severe cases minor or major amputations can be neccessary
Patients' Quality of Life	6-months and 12-month	The quality of life of patient will be evaluated with Foot Function Index from 0 (better) to 170 (worse)
Time back to walk	through study completion, an average of 1 year	It will be registered when patients can go back to walk aftern the intervention
Duration of antibiotic therapy	through study completion, an average of 1 year	systemic antibiotic therapy will be prescribed after intervention and its duration can vary according to infection state.
Number of re-interventions because of the same lesion	through study completion, an average of 1 year	If an infection recur might be necessery to procede with a re-intervention.
Characteristics of surgery	intra-operative	data about characteristics (type) of surgeries will be collected
Length of surgery	intra-operative	data about the lenght (timing) of surgeries will be collected
Rate of recurrences	6-months and 12-month	After intervention bone infections proper of osteomyelitis can recur
Timing of re-interventions because of the same lesion	through study completion, an average of 1 year	If an infection recur might be necessery to procede with a re-intervention.

Trial Locations

Locations (7)

Casa di Cura Abano Terme - POLICLINICO ABANO TERME; 🇮🇹 Abano Terme, Padova, Italy

AUSL Romagna - Ospedale Morgagni Pierantoni; 🇮🇹 Forlì, Italy

ASST Ovest Milanese - Ospedale di Abbiategrasso; 🇮🇹 Abbiategrasso, Milano, Italy

Azienda USL Toscana Nord Ovest - Ospedale Campo di Marte; 🇮🇹 Lucca, Italy

AOU Pisana - Ospedale di Cisanello; 🇮🇹 Pisa, Italy

USL Sud Est Toscana - Ospedale San Donato; 🇮🇹 Arezzo, Italy

ASUGI Azienda Sanitaria Universitaria Giuliano Isontina - Ospedale Monfalcone; 🇮🇹 Monfalcone, Gorizia, Italy