Clinical trial NCT05316298: Diabetic Foot Osteomyelitis Treatment Using Gentamicin-loaded Calcium Sulfate-hydroxyapatite Biocomposite
Official title: Gentamicin-loaded Calcium Sulfate-hydroxyaPatite Biocomposite to tREat Diabetic Foot Ulcers Complicated by oSteomyElitis: a pRospectiVE Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetic Foot Ulcer
Osteomyelitis
Diabetes Mellitus
Keywords: Surgical treatment
antibiotic-loaded bone graft substitute
Cerament G
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Ziekenhuisgroep Twente
name: Slingeland Hospital
name: Franciscus Gasthuis
name: UMC Utrecht
name: Rijnstate Hospital
name: Jeroen Bosch Ziekenhuis
name: Reinier de Graaf Groep
name: St. Antonius Hospital
name: St Jansdal Hospital
name: Maasstad Hospital
First posted: 2022-04-07
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

* 18 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

Exclusion Criteria:

* 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 chronic limb Ischemia, defined in accordance with the Wound-, Ischemia-, Foot Infection classification as signs and / or symptoms of peripheral artery disease and a systolic toe pressure \< 30 mmHg and/or a transcutaneous oxygen pressure \< 30 mmHg in the forefoot.Previous revascularisation is no exclusion criterion.
* 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).

Primary outcomes:
measure: Postoperative wound healing
timeFrame: 20 weeks
Secondary outcomes:
measure: Duration to postoperative wound healing
timeFrame: 20 weeks
measure: persistent osteomyelitis postoperatively
timeFrame: 20 weeks
measure: Amputations during follow-up
timeFrame: 20 weeks
measure: Foot Function Index (FFI) scores
timeFrame: 20 weeks
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Almelo
country: Netherlands
facility: Hospitalgroup Twente
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Delft
country: Netherlands
facility: Reinier de Graaf Hospital
city: Doetinchem
country: Netherlands
facility: Slingeland Hospital
city: Harderwijk
country: Netherlands
facility: St. Jansdal Hospital
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: University Medical Center Groningen
name: Kor H. Hutting, M.D.
role: PRINCIPAL_INVESTIGATOR
References: