Biomarkers in Patients With Flesh-eating Bacterial Infections

NCT ID: NCT02180906

Last Updated: 2016-02-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 169 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2016-02-29

Brief Summary

The purpose of this study is to investigate the immune response in patients with necrotizing soft tissue infections (NSTI). The investigation will focus on inflammatory and vasoactive biomarkers as prognostic markers of severity and mortality at admission to Rigshospitalet and the following 3 days

Detailed Description

Necrotizing soft tissue infection (NSTI) is a complex, multi-factorial disease with diverse microbiological etiology and varying co-morbidities. The rapidly spreading infection may cause extensive soft tissue damage, limb loss, and multiple organ failure. The incidence of NSTIs has increased over the past years and the fatality rates are still high despite increased focus on these patients (20-30%). The extensive inflammatory response is thought to be a main course of death. However, it is unknown which biomarkers that are responsible for the deleterious effects and how these molecular mediators are modulated during the infection and treatment regimes. Thus, there is a need for novel insight into the immune system disturbances in order to improve outcome of NSTIs.

Location: Copenhagen University Hospital, Rigshospitalet, Denmark.

Design: Observational cohort study.

Cohort: NSTI patients in Denmark.

Controls: 50-100 Patients undergoing elective, orthopedic surgery at Rigshospitalet.

Biomarkers: The investigators will focus on three major groups of biomarkers: Acute-phase proteins, cytokines and vasoactive biomarkers.

Sample size calculations:

1. Acute-phase proteins: The investigators expect a mean PTX3-concentration at admission at 120 nmol/L in patients without septic shock and a mean PTX3-concentration at 210 nmol/L in patients with septic shock. With an estimated standard deviation at 100 nmol/L, the inclusion of 52 patients will be able to detect a significant difference with a statistical power of 90% at a 5% significance level. Since the groups are unequal the investigators will need to include 82 patients (N'=52(1+4)^2/4*4).

2. Cytokines: In a pilot study with seven NSTI patients, the investigators found a minimal clinically relevant difference in IL-6 concentration in NSTI patients with LRINEC < 6 and ≥ 6 to be 1050 pg/ml. With an estimated standard deviation at 2000 pg/ml, the inclusion of 114 patients will be able to detect a significant difference with a statistical power of 80% at a 5% significance level.

3. Vasoactive proteins: The investigators expect a mean NOx-concentration at admission at 90 μmol/L in patients without septic shock and a mean NOx-concentration at 145 μmol/Lin patients with septic shock. With an estimated standard deviation at 70 μmol/L, the inclusion of 70 patients will be able to detect a significant difference with a statistical power of 90% at a 5% significance level. Since the groups are unequal the investigators will need to include 110 patients (N'=70(1+4)^2/4*4).

Data: Data will be handled according to the National Data Protection Agency. All original records (incl. consent forms and questionnaires) will be archived at trial site for 15 years. The National Data Protection Agency has approved the biobank (2007-58-0015, J. nr. 30-1282).

Ethics: The trial will adhere to the Helsinki Declaration and Danish law. The National Ethics Committee and the Regional Ethics Committee have approved the inclusion of the NSTI patients (CVK-1211709) and the control patients, including biomarker analyses (H-2-2014-071).

Biomarker analyses, data extraction and interpretation will be performed once the recruiting of participants has ended.

Conditions

Necrotizing Soft Tissue Infection; Necrotizing Fasciitis; Gas Gangrene; Fournier Gangrene

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with NSTI

Definition: An infection that requires acute hospitalization with intensive care treatment and/or surgery as a consequence of severe soft tissue infection in subcutis, muscle and/or fascia and are spreading along tissue structures.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Necrotizing soft tissue infection based on surgical findings
• Age >18 years
• Admitted to/planned to be admitted to the ICU at Rigshospitalet and/or operated for NSTI at Rigshospitalet

• Patients undergoing elective orthopedic surgery (non-pathologic fractures, joint replacement surgery, back surgery) at Rigshospitalet
• Age >18 years

Exclusion Criteria

• Patients who at the operating theatre were categorized as non-NSTI patients

• Patients with ongoing infections

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seventh Framework Programme

OTHER

Sponsor Role: collaborator

Ole Hyldegaard

OTHER

Sponsor Role: lead

Responsible Party

Ole Hyldegaard

Ole Hyldegaard

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marco Bo Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Ole Hyldegaard, MD, PhD

Role: STUDY_DIRECTOR

Rigshospitalet, Denmark

Locations

Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Countries

Denmark

References

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PMID: 15817551 (View on PubMed)

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Reference Type: BACKGROUND

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Kristensen MK, Hansen MB, Madsen MB, Hansen CB, Pilely K, Hyldegaard O, Garred P. Complement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study. Front Immunol. 2020 Jan 31;11:17. doi: 10.3389/fimmu.2020.00017. eCollection 2020.

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Hansen MB, Rasmussen LS, Garred P, Bidstrup D, Madsen MB, Hyldegaard O. Pentraxin-3 as a marker of disease severity and risk of death in patients with necrotizing soft tissue infections: a nationwide, prospective, observational study. Crit Care. 2016 Feb 15;20:40. doi: 10.1186/s13054-016-1210-z.

Reference Type: DERIVED

PMID: 26880104 (View on PubMed)

Hansen MB, Simonsen U, Garred P, Hyldegaard O. Biomarkers of necrotising soft tissue infections: aspects of the innate immune response and effects of hyperbaric oxygenation-the protocol of the prospective cohort BIONEC study. BMJ Open. 2015 May 11;5(5):e006995. doi: 10.1136/bmjopen-2014-006995.

Reference Type: DERIVED

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Related Links

http://www.fp7infect.eu

Research website: INFECT-study. Further description of funding from EU 7th Framework Programme

Other Identifiers

BIONEC1-MBH-2014

Identifier Type: -

Identifier Source: org_study_id