To evaluate the efficacy and safety of EHSG-KF in comparison to meshed STSG in children with partial deep dermal and full thickness burns. Primary Objective: To evaluate the efficacy of EHSG-KF in comparison to meshed STSG based on:• Ratio of…
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Brief title
Condition
- Other condition
Synonym
Health condition
ernstige brandwonden
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
Efficacy evaluation, as a comparison between the EHSG-KF and control sites,
based on:
• Ratio of covered surface area to biopsy site/donor site surface area at visit
6(28 +/-3 days post grafting)
Secondary outcome
First secondary efficacy endpoint:
• % Epithelialization at:
o visit 8 (90 ± 5 days post grafting)
Secondary Endpoints
Safety and efficacy evaluation, as a comparison between the EHSG-KF and
control sites, based on:
• Main secondary safety endpoint:
Clinical and microbiologic signs of infection at visits 4 (6-10 days post
grafting) and 5 (21 +/-2 days post grafting)
• Main secondary efficacy endpoints:
Scar quality at the study areas
Assessment of elasticity of the study areas using the Cutometer® at visit 10
(1 year +/-30 days post grafting)
o Assessment of general scar quality at the study areas using the POSAS, a
reliable and validated scar assessment tool, at visit 10 (1 year +/-30 days
post grafting)
• Other secondary safety endpoint:
Assessment and reporting of all observed adverse events will be carried out
for the full duration of the study from visit 2 on
• Other secondary efficacy endpoint:
Epithelialization at visit 6 (28 +/-3 days post grafting)
Background summary
The management of severe burns remains a significant challenge. The current
gold standard, excision and coverage with meshed STSG, is limited by both donor
site availability and the risk of disfiguring and functionally debilitating
scars. The introduction of cultured epithelial autografts (CEA) has helped
address donor site limitations; however, thirty years since its introduction,
despite tremendous research efforts, CEA continues to yield unacceptable
results when used independently for the coverage of deep burns. The role of CEA
in contemporary burn care is, therefore, largely adjunctive, as is the case
with other keratinocyte replacement techniques, such as keratinocyte spray.
The clinical introduction of now widely used dermal regeneration templates
(e.g. IntegraDRT® and Matriderm®) has pushed the frontiers further, with
potential for improved aesthetic and functional results. However, such
templates still require coverage with an overlying skin graft. The evolution of
an autologous tissue-engineered skin substitute, such as EHSG-KF, that can be
used as an alternative to a STSG, represents the next step towards achieving
coverage of severe burns with limited donor sites, thereby offering a
potentially lifesaving therapy.
EHSG-KF is a tissue-engineered autologous dermo-epidermal skin substitute for
the treatment of partial deep dermal and full thickness skin burns.
The proposed phase IIb clinical trial aims to evaluate the safety and efficacy
of EHSG-KF in adult patients with severe burns, when compared to meshed STSG,
the current gold standard.
Study objective
To evaluate the efficacy and safety of EHSG-KF in comparison to meshed STSG in
children with partial deep dermal and full thickness burns.
Primary Objective: To evaluate the efficacy of
EHSG-KF in comparison to meshed STSG based on:
• Ratio of covered surface area to biopsy site/donor site surface area 4 weeks
post grafting
First Secondary Objective
• % Epithelialization at 3 months post grafting
Secondary Objectives:
To evaluate the safety and efficacy of EHSG-KF in comparison to meshed STSG
based on the assessment of:
• Infection
• Scar quality:
o Cutometer® 3, 6, 12, 24 and 36 months post grafting
o DSM ColorMeter® 3, 6, 12, 24 and 36 months post grafting
o POSAS-questionnaire 3, 6, 12, 24 and 36 months post grafting
• Graft take at 6-10 days post grafting
• %Epithelialization (to estimate *time to complete epithelialization*) at 3
and 4 weeks, and 2 and 6 months post grafting
• Incidence of wound closure at 8 and 12 weeks post grafting
• Assessment and reporting of all observed adverse events
• QOL assessment (EQ-5D and BSHS-B)
• Healthcare resource utilization (direct and indirect healthcare costs, this
questionnaire will not be handed out to patients)
Study design
Open label, intra-patient randomised controlled, prospective, multicentre phase
IIb clinical trial
Intra-patient randomization: Two sites, A and B, each an area of 45-90 cm2 are
selected. Each site is covered either with a meshed STSG, or EHSG-KF, and the
type of graft for each site has been determined in advance.
The endpoint measures described above, including ratio of covered surface area
to harvested surface area and presence of infection, will be determined for
each site, and comparisons made
Intervention
Product:
EHSG-KF is an autologous tissue-engineered dermo-epidermal skin substitute on
a collagen type I hydrogel. The size per graft is 45±4cm2 and the thickness is
0.5-2 mm.
Intervention:
Grafting of the wound bed (=experimental area) with 1 to 2 grafts of EHSG-KF
Product (control):
Autologous split-thickness skin graft (STSG) meshed at a ratio of 3:1
Intervention:
Grafting of the control wound bed (=control area) with meshed STSG, whereby
size of control area=size of experimental area
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness (if applicable): Klik voor meer informatie
The experimental product potentially offers a better therapeutic option than
STSG alone. EHSG-KF has been successfully tested in the phase I clinical trial
and several preclinical studies without significant adverse reactions and, as
the skin grafts are autologous, no unusually high incidence of
complications/adverse effects is anticipated. If the working hypothesis proves
true, then graft take and wound healing dynamics will be similar to those of
STSG, while the efficacy, in terms of scar quality and final functional and
cosmetic results, will be even better than obtained from STSG alone. Currently
the product is under investigation and ongoing risk will be assessed and risk
mitigation strategies are included in the study protocol. Based on the
available study results, we do not believe the risk associated with this
product is greater than the usual treatment.
Grabenstrasse 11
Schlieren 8952
CH
Grabenstrasse 11
Schlieren 8952
CH
Listed location countries
Age
Inclusion criteria
• Age: <12 years of age
• Deep partial thickness and/or full-thickness burns requiring surgical
wound coverage
• Expected that >=90 cm2 of wound (not counting the head and neck area
for study patients in The Netherlands) will remain open at 4 weeks post
burn despite proceeding with treatment in accordance with the standard
of care. >20% TBSA burns can be taken as guideline, but TBSA is not an
inclusion criterion.
• Signed informed consent from the patient or the parents/legally authorized
representative.
Exclusion criteria
Patients tested positive for HBV, HCV, syphilis or HIV
• Patients with known underlying or concomitant medical conditions that may
interfere with normal wound healing (e.g. systemic skin and connective tissue
diseases, any kind of congenital defect of metabolism including
insulin-dependent diabetes mellitus, Cushing syndrome or disease, scurvy,
chronic hypothyroidism, congenital or acquired immunosuppressive condition,
chronic renal failure, or chronic hepatic dysfunction (Child-Pugh class B or
C), severe malnutrition, or other concomitant illness which, in the opinion of
the Investigator, has the potential to significantly delay wound healing)
• Severe drug and alcohol abuse
• Pre-existing coagulation disorders as defined by INR outside its normal
value, PTT >ULN and fibrinogen / or at the Investigator*s discretion
• Patients with known allergies to amphotericin B, gentamicin, penicillin or
streptomycin or bovine collagen
• Previous enrolment of the patient into the current phase II study
• Participation of the patient in another study with conflicting endpoints
within 30 days preceding and during the present study
• Patients or parents/legal guardian expected not to comply with the study
protocol (including patients with severe cognitive dysfunction/impairment and
severe psychiatric disorders)
• Pregnant or breast feeding females
• Suspicion of non-accidental injury
•Wounds in the head and neck area as study target area (only applicable
for study patients in The Netherlands)
• Enrolment of the Investigator, his/her family members, employees and other
dependent persons
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2017-002461-21-NL |
| CCMO | NL62416.000.17 |