Study on the Effectiveness of Hypothermal Sulphurous Water in Wound Hygiene

Официальное название

Pilot Study on the Effectiveness of Sulphurous Thermal Water in Wound Hygiene: Spa Wound Care

Обзор

This is an interventional double arms pilot study on the effectiveness of hydrogen sulfide (H2S) rich and microbiologically pure spa sulphurous water, in the wound hygiene of hard-to heal wounds, set in an italian spa facility. At least 24 subjects enrolled according to selection criteria will be 1:1 randomized in two intervention groups: the former (A) undergoing pack of sulphurous water on soaked gauzes for 20 minutes, the latter (B) undergoing full limb immersion for 20 minutes. Differences among the two arms will be assessed as changes in wound microbiome, wound pH, Trans epidermal water loss (TEWL), 1000x ex-vivo microscope imaging, wound fluorescence imaging for bacterial colonization and longitudinal shifts in wound sizing and peculiar features according to the Bates-Jensen Wound Assessment Tool (BWAT). Time required for re-epithelization will be recorded together with any adverse reactions or events for both arms and compared. The study aims at assessing the effectiveness of hydrogen sulfide exogenous supply on infected or colonized hard to heal wounds and which way of administration (pack Vs immersion) could have prevailing effects.

Подробное описание

The effectiveness of sulphurous thermal waters in the treatment of complex or difficult wounds has been known since ancient times.

In recent years, the increase in life expectancy, the aging of the population and survival of chronically ill subjects lead to the outbreak of "hard to heal" wounds presenting multi drug resistant germs (MDR). Recent studies have shown that the effectiveness of thermal waters is not only related to the presence of dissolved ions but, as in the case of sulphurous ones, to the presence of hydrogen sulfide, a gas transmitter that diffuses freely through the skin, eliciting local and systemic effects. This molecule, present in sulphurous waters within specific pH and temperature ranges, is able to promote the healing of acute, chronic and infected wounds. H2S also exerts a powerful antibacterial and antifungal effect by transforming into pentationic acid (H2S5O6). In addition, the specific microbiome of each thermal source has the ability to interact with the skin microbiome and prevails over wound biofilm stimulating skin eubiosis. By virtue of these considerations, investigators perform an interventional pilot trial conducted to evaluate the effects of raw sulphurous thermal water, microbiologically pure, in the wound hygiene of acute and chronic wounds, regardless of their aetiology and bacterial colonization.

Outpatients \>18 years, presenting at spa facility with wound respecting selection criteria, will undergo to a wound hygiene protocol based on the use of raw sulphurous thermal water of Acque Albule, tested negative to microbiological analysis for the presence of pathogens. Subjects will be 1:1 randomized in 2 treatment arms: group A receiving sulphurous thermal water pack on soaked gauzes for 20 minutes and group B having their wound/s fully immersed in sulphurous thermal water for 20 minutes. Both arms will be treated every 48 hours up to complete wound re-epithelization. Participants will be submitted just at enrollment to wound microbiological sampling (swab). All parameters worth investigating will be assessed at each session prior to intervention (T0,2,4..) and after (T1,3,5…). Specifically wound microbiome sampling, together with pH, trans epidermal water loss (TEWL) measurements, wound fluorescence bacterial imaging, and ex-vivo microscope imaging will be recorded at each time point. Any adverse events, superinfections will be monitored and properly managed. A three months post-healing follow-up (Tf) will be performed to determine scar quality and possible wound relapse. Results will be expressed in term of intra-session (short term effects) and inter sessions(longitudinal effects) changes (delta) in order to assess the singular and the whole effects of each arm intervention. Finally differences in term of effectiveness among the two interventions will be evaluated.

Вмешательства

• Процедура wound hygiene with hypothermal sulfurous water by packs
  GROUP A: After dressing removal, the wound is exposed. Sulphur thermal water at spring temperature (23°C) is applied for 20 minutes on the untreated wound by packs on non woven gauzes entirely covering the area. Eventually, if dried, gauzes are externally watered with additional sulphurous thermal water during the 20 minutes. After water application the wound follows the other 3 steps of the wound hygiene protocol: non viable tissue removal, edges reactivation and dressing. Non interactive dress
• Процедура wound hygiene with hypothermal sulfurous water by limb full immersion
  GROUP B: After dressing removal, the wound is exposed. Sulphur thermal water at spring temperature (23°C) is applied for 20 minutes on the untreated wound by limb full immersion in a limb tub. After the immersion, the wound follows the other 3 steps of the wound hygiene protocol: non viable tissue removal, edges reactivation and dressing. Non interactive dressings, just for wound moisture management, are used on cleaned wound/s. Dressing fixation, elastic bandages or off-load will be provided wh

Первичные конечные точки

• wound healing rate [Срок оценки: within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Short term Wound bacteria critical colonization [Срок оценки: within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Short term Wound microbiome changes [Срок оценки: within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Short Term Wound bed pH changes [Срок оценки: within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]

Вторичные конечные точки (5)

• Longitudinal Wound microbiome changes during treatment up to re-epithelization [Срок оценки: within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Longitudinal Wound bacterial critical colonization control [Срок оценки: within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Longitudinal Wound bed pH changes [Срок оценки: within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Longitudinal Wound TEWL changes [Срок оценки: within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)]
• Long term re-epithelization stability [Срок оценки: 90 days after wound healing (Tf)]

Критерии участия

Критерии включения

• Patients >18 years old
• Any comorbidities (except very severe I, II immune deficiencies)
• Any systemic drug therapy
• Any associated dressing (except peroxides)
• Acute or chronic wounds requiring wound care treatment
• Genital/oral wounds
• Infected wounds, including MDR pathogens
• Biofilmed wounds

Критерии исключения

• Unexplored fistula
• Enteric fistula
• Exposure of fascia, vessels, bones, organs
• Pyoderma Gangrenosum (monotherapy)
• Implanted or penetrating devices (CVC , Port-a-cath, drainages, peritoneal dialysis, external fixators....etc.)
• Exposed implants(nails, plates, internal defibrillator, Pace maker)
• Local antibiotic therapy (not supported by antibiogram)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• Terme di Roma Acque Albiule — Bagni di Tivoli

Публикации

• Tsuji, Hideo.
• Faga A, Nicoletti G, Gregotti C, Finotti V, Nitto A, Gioglio L. Effects of thermal water on skin regeneration. Int J Mol Med. 2012 May;29(5):732-40. doi: 10.3892/ijmm.2012.917. Epub 2012 Feb 15. PMID 22344563
• Davidelli S, Bassetto F, Vitale M, Scapagnini G. Thermal Waters and the hormetic effects of hydrogen Sulfide on inflammatory arthritis and wound healing. Chapter 10 elsevier https://www.sciencedirect.com/science/article/pii/B9780128142530000103
• Wallace JL, Dicay M, McKnight W, Martin GR. Hydrogen sulfide enhances ulcer healing in rats. FASEB J. 2007 Dec;21(14):4070-6. doi: 10.1096/fj.07-8669com. Epub 2007 Jul 18. PMID 17634391
• Mormile I, Tuccillo F, Della Casa F, D'Aiuto V, Montuori N, De Rosa M, Napolitano F, de Paulis A, Rossi FW. The Benefits of Water from Nitrodi's Spring: The In Vitro Studies Leading the Potential Clinical Applications. Int J Mol Sci. 2023 Sep 5;24(18):13685. doi: 10.3390/ijms241813685. PMID 37761993
• Napolitano F, Postiglione L, Mormile I, Barrella V, de Paulis A, Montuori N, Rossi FW. Water from Nitrodi's Spring Induces Dermal Fibroblast and Keratinocyte Activation, Thus Promoting Wound Repair in the Skin: An In Vitro Study. Int J Mol Sci. 2023 Mar 10;24(6):5357. doi: 10.3390/ijms24065357. PMID 36982430
• Ahmad A, Druzhyna N, Szabo C. Effect of 3-mercaptopyruvate Sulfurtransferase Deficiency on the Development of Multiorgan Failure, Inflammation, and Wound Healing in Mice Subjected to Burn Injury. J Burn Care Res. 2019 Feb 20;40(2):148-156. doi: 10.1093/jbcr/irz007. PMID 30649358
• Benedetti F, Curreli S, Krishnan S, Davinelli S, Cocchi F, Scapagnini G, Gallo RC, Zella D. Anti-inflammatory effects of H2S during acute bacterial infection: a review. J Transl Med. 2017 May 10;15(1):100. doi: 10.1186/s12967-017-1206-8. PMID 28490346

Идентификаторы

NCT: NCT06725797 · VULNOLOGIATERMALE1 · AR12419075FF92A2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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