Predictive Value of Nu.Q™ Biomarkers to Help Guiding the Management of Osteoarticular Infections

Diabetic Foot Clinical Trial

Official title:

Predictive Value of Nu.Q™ Biomarkers to Help Guiding the Management of Osteoarticular Infections - a Monocentric Prospective Observational Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05593874
• Other study ID #: 2022-00140
• Status: Completed
• Start date: October 10, 2022
• Est. completion date: October 31, 2023

Study information

• Verified date: May 2024
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 31, 2023
• Est. primary completion date: August 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults (age = 18 years old) suffering from diabetes mellitus (type 1 or 2)

• Diabetic foot ulcer with severe infection (grade 3 and 4 according to IWGDF 2019 classification)

• Scheduled surgical debridement

Exclusion Criteria:

• Spondylodiscitis

• Pregnant or lactating women

• Previous enrolment in a clinical trial

• Consent declined by participant or tutor in case of incapacitation

• Tutor cannot be reached for consent in case of incapacitation

Related Conditions & MeSH terms

• Arthritis, Infectious
• Chronic Osteomyelitis
• Diabetic Foot
• Infections
• Osteomyelitis
• Septic Arthritis

Intervention

Diagnostic Test:
• Histones H3.1 blood levels
Measure of blood concentrations of histone subtype H3.1

Locations

Country	Name	City	State
Switzerland	University Hospitals Geneva	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical failure	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%	day 30 and day 60
Secondary	Mortality	Death during the study period from day-1 (day of the 1st intervention)	day 30 and day 60
Secondary	Amputation rate	Frequency of the event 'amputation' as incidence rate from day-1 (day of the 1st intervention)	day 1 to day 60
Secondary	Additional surgical interventions rate	Frequency of the event 'additional surgical intervention' (i.e., debridement, amputation) as incidence rate from day-1 (day of the 1st intervention)	day 1 to day 60
Secondary	Time-to-amputation	Measured in days from day-1 (day of the 1st intervention)	day 1 to day 60
Secondary	Time-to-additional-intervention	Measured in days from day-1 (day of the 1st intervention)	day 1 to day 60