Relationship Between Neutrophil Function and Sepsis in Adults and Children With Severe Thermal Injuries

NCT04693442 | Unknown

• 2 other identifiers: RRK5814IRAS Project ID 200366
• Study Type: observational
• Target: 245
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to validate neutrophil function, immature granulocyte and plasma free DNA levels as predictive diagnostic biomarkers of sepsis in burn patients. Inclusion criteria includes healthy volunteers, patients aged 5-15 years old with burns affecting 20% or less Total Body Surface Area (TBSA) and patients aged 16 or above with burns affecting \>15% TBSA. The study involves taking blood, tissue and urine samples.

Conditions

Burns

Outcome Measures

Primary Outcomes (1)

• Diagnosis of sepsis

  Sepsis will be evaluated according to the 2007 American Burn Association (ABA) diagnostic criteria for sepsis in burns. Specifically, sepsis will be diagnosed when 3 of the following criteria are met along with a positive bacterial culture or when evidence of a clinical response to antibiotics is detected: 1. Temperature (\>39°C or \<36°C) 2. progressive tachycardia (\>110 beats per minute 3. progressive tachypnea (\>25 breaths per minute not ventilated or minute ventilation \>12 L/minute ventilated) 4. thrombocytopenia (\<100,000/μl; not applied until 3 days after initial resuscitation) 5. hyperglycaemia (untreated plasma glucose \>200 mg/dl, \>7 units of insulin/hr intravenous drip, or \>25% increase in insulin requirements over 24 hours) 6. feed intolerance \>24 hours (abdominal distension, residuals two times the feeding rate, or diarrhoea \>2500 ml/day)

  2 years

Secondary Outcomes (7)

• In-hospital mortality

  2 years

• Predictive mortality scores

  2 years

• Multiple Organ Failure/dysfunction syndrome (MOF/MODS)

  2 years

• Thromboembolic complications

  2 years

• Vancouver Scar Scale (VSS)

  2 years

Study Arms (2)

Burn patients

with the condition

Other: taking of blood, urine and blood samples and objective scar assessment

Control group

without the condition (blood sampling only for adults) and children undergoing general anaesthetic procedures that involve skin resections (blood sampling and excised skin)

Interventions

taking of blood, urine and blood samples and objective scar assessment OTHER

blood, urine and skin tissue sampling \& scar assessment questionnaires

Burn patients

Eligibility Criteria

• Age: 1 Year - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects will be admitted to any Burn Centre participating in the study. This includes but not limited to: Queen Elizabeth Hospital Birmingham; Birmingham Children's Hospital; Mid Essex NHS Trust, Broomfield Hospital, Chelmsford The patients will be new burns patients presented within 24 hours of thermal injury. They will be identified by the admitting doctor from the Burns Team.

You may qualify if:

• Patients aged 1-15 years admitted with a ≥20%TBSA
• Patients aged 16 and over admitted with a ≥15% TBSA
• Patients presented within 24 hours of thermal injury

You may not qualify if:

• Associated multiple injuries with Injury severity score \> 25
• Decision not to treat made on admission due to the severity of the injury
• Patients with chemical and deep electrical burns
• Premorbid conditions
• Active Malignancy
• Patients receiving glucocorticoid treatment
• Multiple limb amputations
• Patients with known long term infections (i.e., Hepatitis B \& C, Human Immune Deficiency \[HIV\])

Sponsors & Collaborators

• University Hospital Birmingham NHS Foundation Trust: lead
• The Scar Free Foundation: collaborator
• University of Birmingham: collaborator

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

Related Publications (15)

• Farina JA Jr, Rosique MJ, Rosique RG. Curbing inflammation in burn patients. Int J Inflam. 2013;2013:715645. doi: 10.1155/2013/715645. Epub 2013 May 20.

  PMID: 23762773 BACKGROUND

• Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, Hayden DL, Hennessy L, Moore EE, Minei JP, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Brownstein BH, Mason PH, Baker HV, Finnerty CC, Jeschke MG, Lopez MC, Klein MB, Gamelli RL, Gibran NS, Arnoldo B, Xu W, Zhang Y, Calvano SE, McDonald-Smith GP, Schoenfeld DA, Storey JD, Cobb JP, Warren HS, Moldawer LL, Herndon DN, Lowry SF, Maier RV, Davis RW, Tompkins RG; Inflammation and Host Response to Injury Large-Scale Collaborative Research Program. A genomic storm in critically injured humans. J Exp Med. 2011 Dec 19;208(13):2581-90. doi: 10.1084/jem.20111354. Epub 2011 Nov 21.

  PMID: 22110166 BACKGROUND

• Jackson PC, Hardwicke J, Bamford A, Nightingale P, Wilson Y, Papini R, Moiemen N. Revised estimates of mortality from the Birmingham Burn Centre, 2001-2010: a continuing analysis over 65 years. Ann Surg. 2014 May;259(5):979-84. doi: 10.1097/SLA.0b013e31829160ca.

  PMID: 23598383 BACKGROUND

• Mann EA, Baun MM, Meininger JC, Wade CE. Comparison of mortality associated with sepsis in the burn, trauma, and general intensive care unit patient: a systematic review of the literature. Shock. 2012 Jan;37(1):4-16. doi: 10.1097/SHK.0b013e318237d6bf.

  PMID: 21941222 BACKGROUND

• Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.

  PMID: 12682500 BACKGROUND

• Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004 Mar 5;303(5663):1532-5. doi: 10.1126/science.1092385.

  PMID: 15001782 BACKGROUND

• Mocsai A. Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med. 2013 Jul 1;210(7):1283-99. doi: 10.1084/jem.20122220.

  PMID: 23825232 BACKGROUND

• Butler KL, Ambravaneswaran V, Agrawal N, Bilodeau M, Toner M, Tompkins RG, Fagan S, Irimia D. Burn injury reduces neutrophil directional migration speed in microfluidic devices. PLoS One. 2010 Jul 30;5(7):e11921. doi: 10.1371/journal.pone.0011921.

  PMID: 20689600 BACKGROUND

• Arturson G. Neutrophil granulocyte functions in severely burned patients. Burns Incl Therm Inj. 1985 Jun;11(5):309-19. doi: 10.1016/0305-4179(85)90093-2.

  PMID: 4027746 BACKGROUND

• Bjerknes R, Vindenes H, Laerum OD. Altered neutrophil functions in patients with large burns. Blood Cells. 1990;16(1):127-41; discussion 142-3.

  PMID: 2190644 BACKGROUND

• Jones CN, Moore M, Dimisko L, Alexander A, Ibrahim A, Hassell BA, Warren HS, Tompkins RG, Fagan SP, Irimia D. Spontaneous neutrophil migration patterns during sepsis after major burns. PLoS One. 2014 Dec 9;9(12):e114509. doi: 10.1371/journal.pone.0114509. eCollection 2014.

  PMID: 25489947 BACKGROUND

• The World Health Organisation. Burns [updated April 2014; cited 2015 06.10.2015]. Available from: http://www.who.int/mediacentre/factsheets/fs365/en/.

  BACKGROUND

• Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685-705. doi: 10.1146/annurev-physiol-030212-183653. Epub 2012 Nov 8.

  PMID: 23140366 BACKGROUND

• Tullie S, Asiri A, Acharjee A, Moiemen NS, Lord JM, Harrison P, Hazeldine J. Day One Cell-Free DNA Levels as an Objective Prognostic Marker of Mortality in Major Burns Patients. Cells. 2025 Jun 1;14(11):821. doi: 10.3390/cells14110821.

  PMID: 40497997 DERIVED

• Hazeldine J, McGee KC, Al-Tarrah K, Hassouna T, Patel K, Imran R, Bishop JRB, Bamford A, Barnes D, Wilson Y, Harrison P, Lord JM, Moiemen NS. Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study. BMJ Open. 2021 Oct 22;11(10):e052035. doi: 10.1136/bmjopen-2021-052035.

  PMID: 34686556 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

skin tissue, serum, plasma

MeSH Terms

Conditions

Burns

Interventions

Urination; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Naiem Moiemen, Surgeon

  The Scar Free Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Bamford, Registered Nurse

CONTACT

01213718226; Amy.Bamford@uhb.nhs.uk

Minnie Ventura, MSc

CONTACT

01213718220; Maximina.Ventura@uhb.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Burns and Plastics Consultant

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: January 5, 2021
• Study Start: November 18, 2016
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: January 5, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)