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

Burns Clinical Trial

— SIFTI-2  

Official title:

A Multi-centre, Prospective Study to Examine the Relationship Between Neutrophil Function and Sepsis in Adults and Children With Severe Thermal Injuries

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04693442
• Other study ID #: RRK5814
• Secondary ID: IRAS Project ID
• Status: Recruiting
• Start date: November 18, 2016
• Est. completion date: January 31, 2022

Study information

• Verified date: December 2020
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: Amy Bamford, Registered Nurse
• Phone: 01213718226
• Email: Amy.Bamford[@]uhb.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The initial cohort for SIFTI-2 will be generated from patients attending the Birmingham Burns Centre at Queen Elizabeth Hospital Birmingham (QEHB) and Birmingham Children's Hospital (BCH). The cohort will be comprised of patients with moderate and severe burns (injury to more than 15% of the body surface area [TBSA] in adults and 20% TBSA in children). The investigators currently treat between 30-40 patients in this category each year. In order to thoroughly characterise the longitudinal neutrophil response to burn injury and to investigate its potential relationship with outcome post-burn, the ivestigators will measure the genomic, phenotypic and functional response of peripheral blood neutrophils across time in burn-injured patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 245
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 99 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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])

Related Conditions & MeSH terms

• Burns
• Sepsis

Intervention

Other:
• taking of blood, urine and blood samples and objective scar assessment
blood, urine and skin tissue sampling & scar assessment questionnaires

Locations

Country	Name	City	State
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust	The Scar Free Foundation, University of Birmingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (13)

Arturson G. Neutrophil granulocyte functions in severely burned patients. Burns Incl Therm Inj. 1985 Jun;11(5):309-19. — View Citation

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

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Mócsai 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. Review. — View Citation

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

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, López 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: Temperature (>39°C or <36°C); progressive tachycardia (>110 beats per minute; progressive tachypnea (>25 breaths per minute not ventilated or minute ventilation >12 L/minute ventilated); thrombocytopenia (<100,000/µl; not applied until 3 days after initial resuscitation); hyperglycaemia (untreated plasma glucose >200 mg/dl, >7 units of insulin/hr intravenous drip, or >25% increase in insulin requirements over 24 hours); feed intolerance >24 hours (abdominal distension, residuals two times the feeding rate, or diarrhoea >2500 ml/day)	2 years
Secondary	In-hospital mortality	Death while in-hospital	2 years
Secondary	Predictive mortality scores	Predictive mortality scores are measured by Revised Baux Score, Abbreviated Burn Severity Index (ABSI), and APACHE II	2 years
Secondary	Multiple Organ Failure/dysfunction syndrome (MOF/MODS)	The presence of altered organ function where homeostasis cannot be maintained without intervention using Denver 2 and SOFA scores. For Denver score, MOF is defined as > 3, two (2) organ system involved for 2 consecutive days while in SOFA, MOF> = 4 , two (2) organ system involved for first 24 hours. In the subsequent time points, only cardiac scores for SOFA and Denver 2 are recorded.	2 years
Secondary	Thromboembolic complications	Clinical signs and symptoms associated with thrombosis, i.e., pulmonary embolism, deep vein thrombosis. Clinical investigation to confirm thrombosis will be based on any of the following imaging procedure: CTPA, VQ Scan, USS, Venogram, D-dimer results	2 years
Secondary	Vancouver Scar Scale (VSS)	This scale uses a numerical assessment of four skin characteristics including: Height (range, 0-4), Pliability (range, 0-4), Vascularity (range, 0-3), and Pigmentation (range, 0-3). The assessors choose a numerical value for each of these characteristics based on a comparison with normal skin.	2 years
Secondary	Patient and Observer Scar Assessment Scale	Patient and Observer Scar Assessment Scale (POSAS, version 2.0) - The POSAS questionnaire seeks to measure scar quality and is a subjective scar scale that consists of two parts: a Patient Scale and an Observer Scale. Both scales contain six items that are scored numerically on a ten-step scale and together they make up the 'Total Score' of the Patient and Observer Scale. The POSAS Patient scale assesses the scar in terms of pain, itching, scar colour, stiffness, thickness and irregularity and overall opinion. The POSAS Observer scale assesses the scar in terms of vascularity, pigmentation, thickness, relief, pliability, surface area and overall opinion.	2 years
Secondary	Brisbane Burn Scar Impact Profile	Brisbane Burn Scar Impact Profile (BBSIP, version 1.0) - This questionnaire assesses the health-related quality of life in people with burn scars. It consists of seven parts which measure; (a) the overall impact of burn scars (itch, pain and other sensations, and their impact on the subject), (b) the impact of the burn scars on work and daily activities, (c) the impact of the burn scars on relationships and social interactions, (d) the subjects perception of the impact of the burn scars on their appearance, (e) the subjects emotional reactions towards their scars and (f) the physical symptoms caused by the burn scars.	2 years