Predictive Value of Nu.Q™ Biomarkers to Help Guiding the Management of Osteoarticular Infections
Study Details
Study Description
Brief Summary
Diabetic foot ulcers are frequent with average lifetime risk of 15%, and can lead to bone and joint infections. Current protocols for their management include evaluation of ischemia, assessment of underlying bone infection, sharp debridement, off-loading and use of dressings that promote moist wound healing. Extensive debridement is optimal for wound healing and decreases the risk of recurrence. However, extension of surgical debridement is left at the clinician judgement and thus lacks standardised protocols. Plus, there is currently no known risk factors or specific biomarkers that can help guide the clinician for the extent of debridement or that can predict a recurrence in case of non-extensive debridement. The main objectives of the study are to either unravel a new biomarker, and/or identify risk factors associated with poor prognosis following surgical debridement in diabetic foot ulcers. Histones, more specifically H3.1 subtype, have been associated with sepsis.
The main hypothesis is that higher blood levels of H3.1 will be present in participants showing poor prognosis (i.e., having additional surgeries, amputation, death) and that a rise in H3.1 blood levels compared to baseline (before the 1st surgical intervention) would provide an early warning of relapse or treatment failure.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Diabetic foot ulcer with osteoarticular infections Diabetic patients suffering from ulcer that led to an osteoarticular infection (e.g. chronic osteomyelitis, septic arthritis) |
Diagnostic Test: Histones H3.1 blood levels
Measure of blood concentrations of histone subtype H3.1
|
Outcome Measures
Primary Outcome Measures
- Clinical failure [day 30 and day 60]
Presence of infection (IWGDF 2019 criteria) and No change in H3.1 blood levels from baseline (day -1) or secondary increase after an initial decline ≥ 75%
Secondary Outcome Measures
- Mortality [day 30 and day 60]
Death during the study period from day-1 (day of the 1st intervention)
- Amputation rate [day 1 to day 60]
Frequency of the event 'amputation' as incidence rate from day-1 (day of the 1st intervention)
- Additional surgical interventions rate [day 1 to day 60]
Frequency of the event 'additional surgical intervention' (i.e., debridement, amputation) as incidence rate from day-1 (day of the 1st intervention)
- Time-to-amputation [day 1 to day 60]
Measured in days from day-1 (day of the 1st intervention)
- Time-to-additional-intervention [day 1 to day 60]
Measured in days from day-1 (day of the 1st intervention)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults (age ≥ 18 years old) suffering from diabetes mellitus (type 1 or 2)
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Diabetic foot ulcer with severe infection (grade 3 and 4 according to IWGDF 2019 classification)
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Scheduled surgical debridement
Exclusion Criteria:
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Spondylodiscitis
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Pregnant or lactating women
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Previous enrolment in a clinical trial
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Consent declined by participant or tutor in case of incapacitation
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Tutor cannot be reached for consent in case of incapacitation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Geneva | Geneva | Switzerland | 1211 |
Sponsors and Collaborators
- University Hospital, Geneva
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Eichhorn T, Linsberger I, Laukova L, Tripisciano C, Fendl B, Weiss R, Konig F, Valicek G, Miestinger G, Hormann C, Weber V. Analysis of Inflammatory Mediator Profiles in Sepsis Patients Reveals That Extracellular Histones Are Strongly Elevated in Nonsurvivors. Mediators Inflamm. 2021 Mar 17;2021:8395048. doi: 10.1155/2021/8395048. eCollection 2021.
- Lebrun E, Tomic-Canic M, Kirsner RS. The role of surgical debridement in healing of diabetic foot ulcers. Wound Repair Regen. 2010 Sep-Oct;18(5):433-8. doi: 10.1111/j.1524-475X.2010.00619.x.
- Li Y, Liu B, Fukudome EY, Lu J, Chong W, Jin G, Liu Z, Velmahos GC, Demoya M, King DR, Alam HB. Identification of citrullinated histone H3 as a potential serum protein biomarker in a lethal model of lipopolysaccharide-induced shock. Surgery. 2011 Sep;150(3):442-51. doi: 10.1016/j.surg.2011.07.003.
- Monteiro-Soares M, Russell D, Boyko EJ, Jeffcoate W, Mills JL, Morbach S, Game F; International Working Group on the Diabetic Foot (IWGDF). Guidelines on the classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3273. doi: 10.1002/dmrr.3273.
- Morimont L, Dechamps M, David C, Bouvy C, Gillot C, Haguet H, Favresse J, Ronvaux L, Candiracci J, Herzog M, Laterre PF, De Poortere J, Horman S, Beauloye C, Douxfils J. NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study. Biomolecules. 2022 Jul 27;12(8):1038. doi: 10.3390/biom12081038.
- Thiam HR, Wong SL, Qiu R, Kittisopikul M, Vahabikashi A, Goldman AE, Goldman RD, Wagner DD, Waterman CM. NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7326-7337. doi: 10.1073/pnas.1909546117. Epub 2020 Mar 13.
- Wong SL, Demers M, Martinod K, Gallant M, Wang Y, Goldfine AB, Kahn CR, Wagner DD. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015 Jul;21(7):815-9. doi: 10.1038/nm.3887. Epub 2015 Jun 15.
- 2022-00140