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

NCT05593874 | Completed

• 1 other identifier: 2022-00140
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Foot; Chronic Osteomyelitis; Septic Arthritis

Keywords

diabetic foot; osteoarticular infections

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Mortality

  day 30 and day 60

• Amputation rate

  day 1 to day 60

• Additional surgical interventions rate

  day 1 to day 60

• Time-to-amputation

  day 1 to day 60

• Time-to-additional-intervention

  day 1 to day 60

Study Arms (1)

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

Interventions

Histones H3.1 blood levels DIAGNOSTIC_TEST

Measure of blood concentrations of histone subtype H3.1

Diabetic foot ulcer with osteoarticular infections

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

All diabetic patients fulfilling the inclusion criteria with no exclusion criteria.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

University Hospitals Geneva

Geneva, 1211, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 32176445 BACKGROUND

• 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.

  PMID: 20840517 BACKGROUND

• 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.

  PMID: 32170015 BACKGROUND

• 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.

  PMID: 26076037 BACKGROUND

• 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.

  PMID: 21878229 BACKGROUND

• 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.

  PMID: 33790693 BACKGROUND

• 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.

  PMID: 36008932 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Centrifugated blood samples (serum/plasma used for analyses)

MeSH Terms

Conditions

Diabetic Foot; Arthritis, Infectious

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Subinvestigator

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 25, 2022
• Study Start: October 10, 2022
• Primary Completion: August 18, 2023
• Study Completion: October 31, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)