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

NCT06388603 | Recruiting

• 1 other identifier: DFORCT012023
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 7

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.

Conditions

Osteomyelitis - Foot

Keywords

Diabetic Foot; Osteomyelitis; Forefoot

Outcome Measures

Primary Outcomes (1)

• healing rate

  complete re-epithelization of the lesion, without secretion or drainage, confirmed at two successive follow-up visits.

  6-month

Secondary Outcomes (10)

• Duration of antibiotic therapy

  through study completion, an average of 1 year

• Rate of recurrences

  6-months and 12-month

• Number of re-interventions because of the same lesion

  through study completion, an average of 1 year

• Timing of re-interventions because of the same lesion

  through study completion, an average of 1 year

• Proportion of patients undergoing amputations

  through study completion, an average of 1 year

Study Arms (2)

Standard of Care - Osteomyelitis treatment

ACTIVE COMPARATOR

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.

Other: Standard of Care

Bioactive Glass

EXPERIMENTAL

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.

Device: Bioactive Glass

Interventions

Bioactive Glass DEVICE

Bonalive Granules and Bonalive Putty will be used (according to their IFU and CE certification) to fill the bone void after the debridment of infected tissue as they have osteoconductive and osteostimulative properties that allow bone rigeneration. Moreover, Bonalive Granules also present some bacteria growth inhibiting properties to combact bone infection propoer of Ostemyelitis.

Also known as: Bonalive Granules RDM: 856052; manufacturer code:13120, Bonalive Putty RDM: 855194; manufacturer code:16120

Bioactive Glass

Standard of Care OTHER

The investigators are left free to proceed according to the normal standar procedure they normally use. The procedures can vary according to investigator judgment also depending on the state of Osteomylitis.

Standard of Care - Osteomyelitis treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained.
• Male or female patients \>= of 18 years old.
• They should have type I since at least 5 years or type II DM
• 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.
• 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.
• 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.
• Anatomical area: forefoot.

You may not qualify if:

• They should not have metabolic decompensation as witnessed by HbA1c \>109 mmol/mol (\> 12%).
• They should not have major amputation on the contra-lateral limb.
• They should not have acute or chronic Charcot's foot in the affected foot.
• They should not have undergone surgical or endovascular revascularization in the affected foot in the month preceding the enrollment.
• 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.
• They should not have ESRD in dialysis.
• They should not be bedridden or not ambulating.
• They should not have a life expectancy shorter than one year.
• They should not be too ill to sustain a surgical procedure under loco-regional anesthesia.
• They should not have severe disease which might interfere with the expected course of the disease and therapy.
• Hypersensitivity to any product ingredient(s) or history of anaphylactic reactions.
• Participation in another interventional studies within 45 days prior to the start of the present study.
• Predictable poor compliance or inability to communicate well with the investigator.

Sponsors & Collaborators

• ASST Ovest Milanese: lead
• Hippocrates Research: collaborator
• Bonalive Biomaterials Ltd: collaborator

Study Sites (7)

ASUGI Azienda Sanitaria Universitaria Giuliano Isontina - Ospedale Monfalcone

Monfalcone, Gorizia, 34074, Italy

NOT YET RECRUITING

ASST Ovest Milanese - Ospedale di Abbiategrasso

Abbiategrasso, Milano, 20081, Italy

RECRUITING

Casa di Cura Abano Terme - POLICLINICO ABANO TERME

Abano Terme, Padova, 35031, Italy

NOT YET RECRUITING

USL Sud Est Toscana - Ospedale San Donato

Arezzo, 52100, Italy

NOT YET RECRUITING

AUSL Romagna - Ospedale Morgagni Pierantoni

Forlì, 47121, Italy

NOT YET RECRUITING

Azienda USL Toscana Nord Ovest - Ospedale Campo di Marte

Lucca, 55100, Italy

NOT YET RECRUITING

AOU Pisana - Ospedale di Cisanello

Pisa, 5612, Italy

NOT YET RECRUITING

Related Publications (14)

• De Giglio R, Di Vieste G, Mondello T, Balduzzi G, Masserini B, Formenti I, Lodigiani S, Pallavicini D, Pintaudi B, Mazzone A. Efficacy and Safety of Bioactive Glass S53P4 as a Treatment for Diabetic Foot Osteomyelitis. J Foot Ankle Surg. 2021 Mar-Apr;60(2):292-296. doi: 10.1053/j.jfas.2020.06.029. Epub 2020 Sep 6.

  PMID: 33358382 BACKGROUND

• Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds M, Holstein P, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, van Baal J, van Merode F, Schaper N. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia. 2007 Jan;50(1):18-25. doi: 10.1007/s00125-006-0491-1. Epub 2006 Nov 9.

  PMID: 17093942 BACKGROUND

• Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds M, Holstein P, Jirkovska A, Mauricio D, Tennvall GR, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, Van Baal J, Van Merode F, Schaper N. Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study. Diabet Med. 2008 Jun;25(6):700-7. doi: 10.1111/j.1464-5491.2008.02445.x.

  PMID: 18544108 BACKGROUND

• Lipsky BA, Aragon-Sanchez J, Diggle M, Embil J, Kono S, Lavery L, Senneville E, Urbancic-Rovan V, Van Asten S; International Working Group on the Diabetic Foot; Peters EJ. IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev. 2016 Jan;32 Suppl 1:45-74. doi: 10.1002/dmrr.2699. No abstract available.

  PMID: 26386266 BACKGROUND

• Lalidou F, Kolios G, Drosos GI. Bone infections and bone graft substitutes for local antibiotic therapy. Surg Technol Int. 2014 Mar;24:353-62.

  PMID: 24504740 BACKGROUND

• Hanssen AD. Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop Relat Res. 2005 Aug;(437):91-6. doi: 10.1097/01.blo.0000175713.30506.77.

  PMID: 16056032 BACKGROUND

• Vatan A, Saltoglu N, Yemisen M, Balkan II, Surme S, Demiray T, Mete B, Tabak F; Study Group, Cerrahpasa Diabetic Foot. Association between biofilm and multi/extensive drug resistance in diabetic foot infection. Int J Clin Pract. 2018 Mar;72(3):e13060. doi: 10.1111/ijcp.13060. Epub 2018 Jan 30.

  PMID: 29381248 BACKGROUND

• Lindfors NC, Hyvonen P, Nyyssonen M, Kirjavainen M, Kankare J, Gullichsen E, Salo J. Bioactive glass S53P4 as bone graft substitute in treatment of osteomyelitis. Bone. 2010 Aug;47(2):212-8. doi: 10.1016/j.bone.2010.05.030.

  PMID: 20624692 BACKGROUND

• Peltola M, Aitasalo K, Suonpaa J, Varpula M, Yli-Urpo A. Bioactive glass S53P4 in frontal sinus obliteration: a long-term clinical experience. Head Neck. 2006 Sep;28(9):834-41. doi: 10.1002/hed.20436.

  PMID: 16823870 BACKGROUND

• McAndrew J, Efrimescu C, Sheehan E, Niall D. Through the looking glass; bioactive glass S53P4 (BonAlive(R)) in the treatment of chronic osteomyelitis. Ir J Med Sci. 2013 Sep;182(3):509-11. doi: 10.1007/s11845-012-0895-5. Epub 2013 Jan 5.

  PMID: 23292733 BACKGROUND

• Piaggesi A, Goretti C, Iacopi E, Clerici G, Romagnoli F, Toscanella F, Vermigli C. Comparison of Removable and Irremovable Walking Boot to Total Contact Casting in Offloading the Neuropathic Diabetic Foot Ulceration. Foot Ankle Int. 2016 Aug;37(8):855-61. doi: 10.1177/1071100716643429. Epub 2016 Apr 15.

  PMID: 27083507 BACKGROUND

• Kastrin M, Urbancic Rovan V, Frangez I. Possible Advantages of S53P4 Bioactive Glass in the Treatment of Septic Osteoarthritis of the First Metatarsophalangeal Joint in the Diabetic Foot. J Clin Med. 2021 Mar 15;10(6):1208. doi: 10.3390/jcm10061208.

  PMID: 33803930 BACKGROUND

• Iacopi E, Pieruzzi L, Goretti C, Piaggesi A. Pilot Experience on the Use of S53P4 Bioactive Glass in the Surgical Management of Diabetic Foot Osteomyelitis. Int J Low Extrem Wounds. 2022 Mar;21(1):57-64. doi: 10.1177/1534734620926003. Epub 2020 Jun 8.

  PMID: 32506987 BACKGROUND

• Munukka E, Lepparanta O, Korkeamaki M, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylanen H, Salonen JI, Viljanen MK, Eerola E. Bactericidal effects of bioactive glasses on clinically important aerobic bacteria. J Mater Sci Mater Med. 2008 Jan;19(1):27-32. doi: 10.1007/s10856-007-3143-1. Epub 2007 Jun 14.

  PMID: 17569007 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot; Osteomyelitis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Dr. Roberto De Giglio, Med Doctor

  ASST Ovest Milanese

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Roberto De Giglio, Med Doctor

CONTACT

+39 331 6989775; roberto.degiglio@asst-ovestmi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: April 29, 2024
• Study Start: March 21, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)