Diabetic Foot Osteomyelitis Treatment Using Gentamicin-loaded Calcium Sulfate-hydroxyapatite Biocomposite

NCT05316298 | Unknown

• 1 other identifier: 202200240
• Study Type: observational
• Target: 182
• Locations: 1 country
• Sites: 10

Brief Summary

The amputation risk is high when diabetic foot ulcers, complicated by osteomyelitis, fail to heal after non-surgical standard-of-care treatment. A new treatment regimen has been developed recently and has been proven feasible. This treatment regimen consists of surgical debridement, followed by bone void filling with gentamicin-loaded calcium sulfate-hydroxyapatite biocomposite and closure of soft tissues and skin, in combination with antibiotic therapy and offloading. This treatment regimen has not been investigated prospectively. Therefore, this multicenter prospective cohort study was designed, with the primary objective of investigating postoperative wound healing. Patients with diabetic forefoot ulcers, complicated by osteomyelitis, will be included. The most relevant exclusion criteria are: Severe diabetic foot infection, severe limb ischemia, and foot deformity causing high pressure and friction on the diabetic foot ulcer. After inclusion, subjects will undergo study phase 1, which is observation of the standard-of-care non-surgical treatment. When standard-of-care non-surgical treatment is unsuccessful, subjects will be included in study phase 2, which consists of treatment by surgical debridement of the diabetic foot ulcer and underlying osteomyelitis, followed by bone void filling with gentamicin-loaded calcium sulfate-hydroxyapatite biocomposite and closure of soft tissues and skin, followed by a postoperatieve treatment regimen which involves wound care, 10 days of antibiotic therapy and offloading. The primary outcome measure of this study is the proportion of subjects with post-operative wound healing, which will be investigated clinically and will be objectified by a review panel of blinded, independent experts based on digital photographs. Follow-up will be performed until wound healing or for a maximum of 20 weeks. The primary outcome measure is the proportion of subjects with postoperative wound healing during 20 weeks of follow-up. Secondary outcome measures are: days until postoperative wound healing, proportion of subjects with persistent osteomyelitis post-operatively, proportion of subjects undergoing amputations during follow-up, foot function index scores at inclusion and after 20 weeks follow-up.

Conditions

Diabetic Foot Ulcer; Osteomyelitis; Diabetes Mellitus

Keywords

Surgical treatment; antibiotic-loaded bone graft substitute; Cerament G

Outcome Measures

Primary Outcomes (1)

• Postoperative wound healing

  Macroscopic complete epithelialization of all surgical wounds after removal of sutures and/or staples without drainage for a minimum of 2 weeks.

  20 weeks

Secondary Outcomes (4)

• Duration to postoperative wound healing

  20 weeks

• persistent osteomyelitis postoperatively

  20 weeks

• Amputations during follow-up

  20 weeks

• Foot Function Index (FFI) scores

  20 weeks

Study Arms (1)

PRESERVE protocol

Treatment according to the PRESERVE protocol consists of 2 study phases. Phase 1 consists of standard-of-care non-surgical treatment, performed in accordance with current treatment guidelines, during which the research team performs observations. After failed standard-of care non surgical treatment, subjects will be included in study phase 2 and undergo treatment by surgical debridement of the diabetic foot ulcer and underlying osteomyelitis, followed by bone void filling with gentamicin-loaded calcium sulfate-hydroxyapatite biocomposite and closure of soft tissues and skin, followed by postoperative treatment regimen including woundcare, 10 days of antibiotics and offloading.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In this study, patients will be included who present in one of the 10 participating Dutch hospitals with forefoot diabetic foot ulcers complicated by osteomyelitis and sufficient skin and soft tissues around the ulcer for surgical closure.

You may qualify if:

• years of age or older.
• One or multiple forefoot diabetic foot ulcers complicated by osteomyelitis. The treating physician will diagnose osteomyelitis, based on either positive culture results or histopathologic findings of a bone sample, or on the combination of clinical findings of inflammation and a positive probe-to-bone test or imaging findings (X-ray, MRI) A patient with multiple forefoot DFOs can be included as long as all ulcers are related to osteomyelitis on one location.
• Sufficient soft tissues and skin for primary closure or closure by local tissue transposition after surgical debridement, as judged by the treating physician.
• Written declaration of informed consent

You may not qualify if:

• Acute Charcot neuroarthropathy, which will be diagnosed by the treating physician based on clinical examination and MRI.
• Adequate surgical debridement is possible by performing an amputation, as judged clinically by the treating physician (e.g. DFO on the 4th or 5th digit).
• Contra-indications for the use of gentamicin-loaded calcium sulfate-hydroxyapatite biocomposite, as mentioned by the producer: hypersensitivity to any aminoglycoside antibiotics, myasthenia gravis, severe renal impairment, pre-existing calcium metabolism disorders, pregnancy, and breastfeeding. This information will be investigated using the patient's electronic health record file and verbal verification. Severe renal impairment is defined as chronic kidney disease with an estimated glomerular filtration rate \<30 ml/min/1.73m2 or renal replacement therapy.
• Foot deformities that lead to increased pressure and friction on the site of the ulcer, which can only be adequately managed by surgical correction, as judged clinically by the treating physician.
• Implants in bone affected by osteomyelitis
• Inadequate quality and / or volume of soft tissues and skin for primary closure or closure by local tissue transposition after surgical debridement, as judged by the treating physician.
• No written declaration of informed consent.
• Osteomyelitis on ≥1 separate locations.
• Other infected diabetic foot ulcers.
• Severe communication disabilities as judged by the treating physician, which would interfere with adherence to instructions.
• Severe diabetic foot infection, defined as infection-grade 4 according to the International Working Group on the Diabetic Foot classification.
• Severely immunocompromised state as judged by the treating physician (e.g., neutropenia due to chemotherapy, high doses of corticosteroids, HIV infection with CD4 count \<200 / µl).

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Ziekenhuisgroep Twente: collaborator
• Slingeland Hospital: collaborator
• Franciscus Gasthuis: collaborator
• UMC Utrecht: collaborator
• Rijnstate Hospital: collaborator
• Jeroen Bosch Ziekenhuis: collaborator
• Reinier de Graaf Groep: collaborator
• St. Antonius Hospital: collaborator
• St Jansdal Hospital: collaborator
• Maasstad Hospital: collaborator

Study Sites (10)

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

RECRUITING

Hospitalgroup Twente

Almelo, Netherlands

RECRUITING

Rijnstate Hospital

Arnhem, Netherlands

RECRUITING

Reinier de Graaf Hospital

Delft, Netherlands

RECRUITING

Slingeland Hospital

Doetinchem, Netherlands

RECRUITING

St. Jansdal Hospital

Harderwijk, Netherlands

RECRUITING

St. Antonius Hospital

Nieuwegein, Netherlands

RECRUITING

Franciscus Gasthuis & Vlietland

Rotterdam, Netherlands

RECRUITING

Maasstad Hospital

Rotterdam, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Diabetic Foot; Osteomyelitis; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Endocrine System Diseases; Diabetic Neuropathies; Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kor H. Hutting, M.D.

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kor H. Hutting, M.D.

CONTACT

0031887084232; k.h.hutting@umcg.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 7, 2022
• Study Start: December 1, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: November 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Expected to become available in june 2024 for 10 years.
• Access Criteria: Upon requrest by a professional researcher with a valid research plan.

Locations

NL (10)