The present study is a Phase III Randomized Clinical Trial aiming to evaluate the efficacy of Nile tilapia (Oreochromis niloticus) skin as an occlusive biological dressing in the treatment of superficial partial-thickness burns in adults.
Full Title of Study: “Evaluation of Nile Tilapia (Oreochromis Niloticus) Skin as an Occlusive Biological Dressing in the Treatment of Burn Wounds: Phase III Randomized Controlled Trial”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: October 24, 2018
This is a prospective, randomized, monocentric, open-label, controlled phase III clinical study conducted in Fortaleza, Brazil, from April 2017 to October 2018. The local Institutional Review Board approved the study protocol and informed consent, which was obtained from all participants. The research was conducted in accordance with the 1975 Declaration of Helsinki and its amendments. The study population consisted of 115, both male and female, participants, who were recruited from a local burn treatment center. Inclusion criteria were: age ≥ 18 and ≤60 years; the presence of dermatological wounds caused by superficial partial-thickness burns (SPTB) affecting up to 15% of Total Body Surface Area (TBSA) and with indication for outpatient treatment; the absence of previous treatment for the current burn and an absence of other significant diseases that could impact the volunteer's participation in the study (coronary artery disease, peripheral vascular disease, cancer, diabetes mellitus, among others). Exclusion criteria included hypersensitivity to materials used in the study or to related compounds; history of severe adverse reactions; drug addiction, including alcohol; use of medications that could have an impact on wound healing (e.g., steroids) and pregnancy, labor or miscarriage in the 12 weeks before the scheduled start of treatment. In the test group, the treatment was Nile Tilapia Fish Skin, which have a patent registered at the National Institute of Industrial Property (INPI) under number BR 10 2015 021435 9. Nile Tilapia Fish Skin was subjected to a rigorous process of chemical sterilization, glycerolization and irradiation, followed by microbiological tests for bacteria and fungi, before storage in sterile refrigerated packaging. Prior to its use in the patient, the skin was washed in sterile 0.9% saline for 5 minutes, with this process being repeated three times in a row. In the control group, conventional treatment with silver sulfadiazine cream 1% was applied. Randomization was performed using a predefined computer-generated list, with 57 patients being allocated in the test group and 58 patients being allocated in the control group.
- Device: Nile Tilapia Fish Skin
- In the search of new therapies for burns, the skin of Brazil’s most cultivated fish, the Nile tilapia, which was mostly a waste product (although sometimes used as a resistant material for artisanal handicraft), was suggested as a possibility for the development of a low-cost xenograft. Apart from non-infectious microbiota, Nile Tilapia Fish Skin presented histomorphological similarities with human skin in pre-clinical studies. It was shown to have a deep dermis formed by thick collagen fibers organized on parallel/horizontal and transversal/vertical arrangement and composed, in comparison, by larger amounts of type I collagen. Nile Tilapia Fish Skin did not present variations in its microscopic structure and tensile strength after glycerolization, irradiation and posterior rehydration, recovering its natural consistency after glycerol removal.
- Drug: Silver Sulfadiazine Cream 1%
- Topical antibiotic commonly used for the treatment of superficial and deep partial-thickness burns.
Arms, Groups and Cohorts
- Active Comparator: Silver Sulfadiazine Cream 1%
- In the control group, after cleaning the lesion with tap water and 2% chlorhexidine gluconate, a thin layer of Silver Sulfadiazine Cream 1% was applied and covered with gauze and bandage. The dressing changes occurred every 48 hours. The patients were evaluated every 48 hours for the study parameters.
- Experimental: Nile Tilapia Fish Skin
- In the test group, the treatment was Nile Tilapia Fish Skin, which have a patent registered at the National Institute of Industrial Property (INPI) under number BR 10 2015 021435 9. Nile Tilapia Fish Skin was subjected to a rigorous process of chemical sterilization, glycerolization and irradiation, followed by microbiological tests for bacteria and fungi, before storage in sterile refrigerated packaging. Prior to its use in the patient, the skin was washed thrice in sterile 0.9% saline for 5 minutes, in order to remove glycerol. Regarding application in the study patients, after cleaning the lesion with tap water and 2% chlorhexidine gluconate, Nile Tilapia Fish Skin was applied and covered with gauze and bandage. Throughout the treatment, dressings with Nile Tilapia Fish Skin were only changed if the biomaterial was not properly adhered to the wound bed. The patients were evaluated every 48 hours for the study parameters.
Clinical Trial Outcome Measures
- Number of days for complete reepithelialization of the burn wound
- Time Frame: Day 11
- Number of days until complete reepithelialization of the burn wound, considering application of the first dressing as day zero. Complete reepithelialization was defined as a ≥95% reepithelialization calculated via clinical judgment from the consultant
- Number of dressings performed
- Time Frame: Day 11
- In the control group, a dressing change was defined as the act of cleaning the wound and reapplying the Silver Sulfadiazine Cream 1%, which was performed every 48 hours. In the test group, a dressing change was defined as the act of replacing the Nile Tilapia Fish Skin which did not adhere properly and/or replacing gauze and bandage that is full of exudate.
- Amount of anesthetics used throughout the treatment
- Time Frame: Day 11
- In order to audit analgesic intake, apart from the medication prescription (dipyrone and/or tramadol), the patients received a daily record card. They were asked to take the medication only if they felt pain, always respecting instructions in the prescription, and to register the amount of medication taken and the date on the card. Upon returning for medical evaluation, the remaining medication was checked and compared to the daily record card.
- Treatment cost per patient
- Time Frame: Day 11
- Consumption of materials of the burn treatment center was controlled by the completion of a specific form, an activity performed at the end of each patient visit by the nursing staff. The resources consumed were divided into three categories: a) products used for wound management (either Nile Tilapia Fish Skin or Silver Sulfadiazine Cream 1%); (b) hospital material required for dressing preparation (such as sterile gloves, chlorhexidine, gauze, and bandage); and c) analgesic medication required throughout treatment (dipyrone and/or tramadol). Human resources were not evaluated.
- Pain intensity evaluation via Visual Analogue Scale scores
- Time Frame: Day 1, 3, 5, 7, 9 and 11
- Patients were informed that the left end of the 10 cm horizontal line (with a “0”) represented “no pain” and that the right end (with a “10”) represented the “most severe pain imaginable.” They were asked to make a mark on the line that represented their current pain intensity, and the Visual Analogue Scale pain intensity level was scored by measurement of the distance from the mark to the “no pain” end of the line.
- Pain intensity evaluation via Electronic von Frey
- Time Frame: Day 1, 3, 5, 7, 9 and 11
- In the Electronic von Frey, a rigid tip of 0.7 mm in diameter is connected to an electronic system, which displays the test readings in grams (from 0.1 to 1000 g). Initially, 4 different points around the burn were chosen, each one with a distance of around 1 cm from the wound bed. The tip was applied perpendicularly to the skin surface in each of these points, with the application rate controlled entirely by the observer. The participants gave a verbal signal when the pressure was felt to be unpleasant: this measure was taken as the Mechanical Pain Threshold of that point. Subsequently, the process was repeated in a similar region of the contralateral healthy side of the body. The mean of the measures of the 4 points in each area was taken as the mean Mechanical Pain Threshold of that area. Finally, the difference between the nociception threshold of healthy skin and of the edge of the burn, expressed in grams, was determined.
- Burns Specific Pain Anxiety Scale (BSPAS) scores
- Time Frame: Day 5 and 11
- The Brazilian version of the 9-item Burns Specific Pain Anxiety Scale (BSPAS) was employed. Each item in the BSPAS is scored on a 10 cm visual analogue line with two reference points given values of 0 and 10. The patient is asked how much the assertions relate to their current pain situation, with 0 corresponding to ”not at all” and 10 corresponding to ”the worst imaginable way”. The total score is calculated by adding up the scores for all items, with a maximum of 90 points.
- Burn improvement on the day of dressing removal evaluation
- Time Frame: Day 11
- Assessed via the Clinical Global Impression Scale-Improvement (CGI-I). The CGI-I is evaluated by the physician responsible and answers the following question: “Compared to the patient’s condition at admission to the project, this patient’s condition is: 1 – very much improved since the initiation of treatment; 2 – much improved; 3 – minimally improved; 4 – no change from baseline; 5 – minimally worse; 6 – much worse; 7 – very much worse since the initiation of treatment”.
Participating in This Clinical Trial
- Age ≥ 18 and ≤60 years. – Presence of dermatological wounds caused by superficial partial-thickness burns (SPTB) affecting up to 15% of Total Body Surface Area (TBSA). – Patient with indication for outpatient treatment. Exclusion Criteria:
- Previous treatment for the current burn. – Presence of other significant diseases that could impact the volunteer's participation in the study (coronary artery disease, peripheral vascular disease, cancer, diabetes mellitus, among others). – Hypersensitivity to materials used in the study or to related compounds. – History of severe adverse reactions; drug addiction, including alcohol. – Use of medications that could have an impact on wound healing (e.g., steroids). – Pregnancy, labor or miscarriage in the 12 weeks before the scheduled start of treatment.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 60 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
- Provider of Information About this Clinical Study
- Principal Investigator: Edmar Maciel Lima Júnior, MD, Plastic Surgeon – Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
- Overall Official(s)
- Maria Elisabete A de Moraes, MD, PhD, Study Director, Drug Research and Development Center (NPDM)
Lima-Junior EM, de Moraes Filho MO, Costa BA, Fechine FV, de Moraes MEA, Silva-Junior FR, Soares MFADN, Rocha MBS, Leontsinis CMP. Innovative treatment using tilapia skin as a xenograft for partial thickness burns after a gunpowder explosion. J Surg Case Rep. 2019 Jun 14;2019(6):rjz181. doi: 10.1093/jscr/rjz181. eCollection 2019 Jun.
Costa BA, Lima Júnior EM, de Moraes Filho MO, Fechine FV, de Moraes MEA, Silva Júnior FR, do Nascimento Soares MFA, Rocha MBS. Use of Tilapia Skin as a Xenograft for Pediatric Burn Treatment: A Case Report. J Burn Care Res. 2019 Aug 14;40(5):714-717. doi: 10.1093/jbcr/irz085.
Lima Júnior EM, Moraes Filho MO, Forte AJ, Costa BA, Fechine FV, Alves APNN, Moraes MEA, Rocha MBS, Silva Júnior FR, Soares MFADN, Bezerra AN, Martins CB, Mathor MB. Pediatric Burn Treatment Using Tilapia Skin as a Xenograft for Superficial Partial-Thickness Wounds: A Pilot Study. J Burn Care Res. 2020 Feb 19;41(2):241-247. doi: 10.1093/jbcr/irz149.
Alves APNN, Lima Júnior EM, Piccolo NS, de Miranda MJB, Lima Verde MEQ, Ferreira Júnior AEC, de Barros Silva PG, Feitosa VP, de Bandeira TJPG, Mathor MB, de Moraes MO. Study of tensiometric properties, microbiological and collagen content in nile tilapia skin submitted to different sterilization methods. Cell Tissue Bank. 2018 Sep;19(3):373-382. doi: 10.1007/s10561-017-9681-y. Epub 2018 Jan 29.
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