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

Официальное название

A National, Prospective, Randomized, Multicenter, Controlled Comparison of Bioactive Glass S53P4 Versus Standard of Care Treatment of Diabetic Foot Osteomyelitis in the Forefoot

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Bioactive Glass
  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.
• Другое Standard of Care
  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.

Первичные конечные точки

• healing rate [Срок оценки: 6-month]

Вторичные конечные точки (10)

• Duration of antibiotic therapy [Срок оценки: through study completion, an average of 1 year]
• Rate of recurrences [Срок оценки: 6-months and 12-month]
• Number of re-interventions because of the same lesion [Срок оценки: through study completion, an average of 1 year]
• Timing of re-interventions because of the same lesion [Срок оценки: through study completion, an average of 1 year]
• Proportion of patients undergoing amputations [Срок оценки: through study completion, an average of 1 year]
• Patients' Quality of Life [Срок оценки: 6-months and 12-month]
• Patients' Quality of Life [Срок оценки: 6-months and 12-month]
• Time back to walk [Срок оценки: through study completion, an average of 1 year]
• Characteristics of surgery [Срок оценки: intra-operative]
• Length of surgery [Срок оценки: intra-operative]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 7 центров

• ASUGI Azienda Sanitaria Universitaria Giuliano Isontina - Ospedale Monfalcone — Monfalcone
• ASST Ovest Milanese - Ospedale di Abbiategrasso — Abbiategrasso
• Casa di Cura Abano Terme - POLICLINICO ABANO TERME — Abano Terme
• USL Sud Est Toscana - Ospedale San Donato — Arezzo
• AUSL Romagna - Ospedale Morgagni Pierantoni — Forlì
• Azienda USL Toscana Nord Ovest - Ospedale Campo di Marte — Lucca
• AOU Pisana - Ospedale di Cisanello — Pisa

Публикации

• 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
• 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. PMID 17093942
• 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: 10.111 PMID 18544108
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06388603 · DFORCT012023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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