In this clinical pilot study we want to gather data in order to calculate a power for correct subject group to answer the following research question: to explore the relation between NETs/cfDNA in the blood and NETosis in burn wounds and their…
ID
Source
Brief title
Condition
- Other condition
- Embolism and thrombosis
Synonym
Health condition
Brandwonden
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Burn wound severity will be determined at day of admission (day 0/1), day 2-5
post-burn and at day of surgery (if applicable) or day 10 - 20 post-burn by
clinical evaluation, Laser Doppler Imaging (LDI) (not day 10 - 20), and
(immuno)histochemical analyses in burn skin biopsies. In biopsies taken at the
same time points the occurrence of intra-microvascular thrombi and NETosis will
be quantified. In addition, in blood samples collected simultaneously with
clinical routine lab up to day 30 post-burn, the levels of cfDNA/NETs, DNase1
and endogenous pdC1inh will be quantified. MBL serum levels will be examined
in relation to bacterial presence and wound healing.
From healthy volunteers only blood samples will be collected for the
quantification of cfDNA/NETs, DNase1 and endogenous pdC1inh levels.
Secondary outcome
Correlations/associations between wound deepening, thrombosis/NETosis, levels
of cfDNA/NETs, DNase1 and endogenous pdC1inh will be investigated. In addition,
associations of thrombosis/NETosis with burn wound parameters and
characteristics of the patients collected from the medical file e.g. wound size
(% burned of TBSA), wound closure time, co-morbidities, inhalation trauma,
graft take, length of stay, number of surgical procedures will also be
investigated.
Background summary
Upon burn injury a massive inflammatory reaction is induced, which is initially
essential to combat invading microorganisms, debride the wound from damaged
tissue and regulate the wound healing. However, in burn wound patients this
massive inflammatory response seems to be *uncontrolled* and persist for up to
months after the initial trauma, which not only negatively affects the local
healing process of the burn wound, but additionally exerts systemic effects may
result in e.g. secondary (organ) injury and burn wound extension. In addition,
prevention of microbial contamination and infection is vital for burn wound
care. Bacterial presence can namely result in further wound healing problems.
Part 1. Inflammation and burn wound extension: Neutrophil extracellular traps
in expansion of necrosis of the burn wound In burn wound patients, the
expansion of partial thickness burn wounds to deeper or full thickness burn
wounds in the first 48 hours is a common phenomenon. This post-burn wound
deepening leads to increased tissue loss, delayed healing, more hypertrophic
scarring and contractures, an increased need for surgical excisions and
grafting and an increased chance of burn wound infections and death. Despite
the use of e.g. cerium nitrate and anticoagulants in order to prevent
thrombosis, so far no effective treatment exists to prevent post-burn wound
deepening. We recently found extensive microvascular thrombosis in and around
burn wounds, in both animals and human tissue, which persisted for up to weeks
after the initial burn injury. This coincided with neutrophil extracellular
traps (NETs) formation (i.e. NETosis), the process whereby neutrophils eject
net-like structures of their DNA. NETosis has been shown in general to be a
major initiator of blood coagulation and microvascular damage and may therefore
be a promising therapeutic target in order to prevent microvascular thrombosis
and wound deepening in burn wound patients.
Part 2. Immunological factors of infection
In burn wounds, Staphylococcus aureus and Pseudomonas aeruginosa are the most
frequently isolated microbial species. Deficiency for mannose-binding lectin
(MBL) may predispose patients to colonization and infection. MBL is a
broad-spectrum pattern recognition molecule that plays a role in innate
immunity and in the inflammatory response after skin injury. A low serum level
of MBL together with other comorbid factors may predispose the host to
increased susceptibility to colonization and infection.
Study objective
In this clinical pilot study we want to gather data in order to calculate a
power for correct subject group to answer the following research question: to
explore the relation between NETs/cfDNA in the blood and NETosis in burn wounds
and their prognostic potential with regards to clinical outcome. In addition,
we will investigate whether there are links between the concentration of MBL in
blood, the presence of P. aeruginosa and/or S. aureus in burns and wound
healing problems.
Study design
Prospective observational cohort pilot study.
Study burden and risks
The burden of this study is burned skin biopsy collection, LDI and clinical
assessments, daily/weekly blood withdrawals (combined with clinical routine
sampling as much as possible).
The collection of skin biopsies will take place at day of admission (day 0/1),
at day 2 - 5 post-burn and at day of surgery (if applicable) or at day 10 - 20
post-burn.
Clinical parameters e.g. pain and wound healing parameters will be assessed
during routine clinical assessments.
The burden of the study for healthy volunteers is limited to two blood
withdrawals via venepunctures.
De Boelelaan 1108
Àmsterdam 1081 HZ
NL
De Boelelaan 1108
Àmsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
- >= 18 years
- Acute burns
- Competent and temporarily incompetent patients
- Informed Consent by patient or the legal representative
- Admitted to the Burn Center of the Red Cross Hospital in Beverwijk, who are
expected to be admitted at least until the second measurement moment
- No acute psychiatric disorders
- Sufficient Dutch proficiency
Healthy volunteers:
- >= 18 years
- Competent
- Informed Consent
- Sufficient Dutch proficiency
Exclusion criteria
Patients:
- Known underlying diseases: cancer, immune deficiency, hypertension,
complement, thrombosis disorder.
Healthy volunteers:
- Pregnancy or lactating
- Any medication except contraceptives
- Known underlying diseases: cancer, immune deficiency, hypertension,
complement, thrombosis disorder.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77890.029.21 |