Evaluation of Combinational Use of Negative Pressure Wound Therapy (NPWT) for Diabetic Foot Wounds

Official title

Prospective, Multi-Center Randomized Controlled Trial for the Combinational Use of Negative Pressure Wound Therapy (NPWT) for the Treatment of Diabetic Wounds

Overview

Singapore has one of the world's highest diabetes-related lower limb amputation rates in the world. Between 2008 - 2017, 4724/5306 (89.0%) of all major amputations and 6656/7227 (92.1%) of all toe/ray amputations performed in Singapore were for diabetic patients. Diabetic foot ulcers are generally slow to heal and poor wound management may lead to infection and subsequently major amputations. Hence, adequate wound care to achieve wound healing efficiently and effectively is of utmost importance. In the investigators' clinical practice, Negative Pressure Wound Therapy has been the dressing of choice to aid wound closure and prevent infective complications. Drainage of wound exudates helps to reduce and prevent infection, promote granulation tissue proliferation and induce cell growth. When used in combination with dermal substitutes, graft uptake is improved by further promoting proliferation and encouraging tissue regeneration. Wounds can also be closed surgically though primary closure, where the skin is closed and serves as a physical barrier against infection. The technique is not without its pros and cons. Primary closure may decrease healing time and reduce need for additional surgery, but these patients are also at risk of recurrent infection and may require more proximal amputation. These may be circumvented with delayed primary closure, which is the surgical closure of the amputation wound at a delayed timing after amputation. This gives the clinical team time to optimize the wound and ensure that there is no underlying infection prior to closure. The experience of NPWT + Kerecis Omega 3 and delayed primary closure have been positive. To the investigators' current knowledge, there is only one case series reported for the use of fish skin graft in combination with NPWT for the treatment of acute pediatric wounds and two case series for the use of NPWT in diabetic foot wound that has undergone surgical closure. The proposed study would be the first RCT to evaluate effects of combination therapy in both open and closed diabetic foot ulcers.

Interventions

• Device Negative Pressure Wound Therapy
  NPWT applied over wound without any adjuncts
• Device Kerecis
  Kerecis Omega3 Wound Dressing is derived from fish skin and is used as a dermal substitute.
• Device Delayed primary closure with local flap
  Delayed primary closure with local flap to close wound

Primary outcome measures

• Number of 100% Wound Closure at 12 weeks [Time frame: 12 weeks post-intervention]

Secondary outcome measures (6)

• Time in days taken to achieve complete wound closure [Time frame: Up to 12 weeks post-intervention]
• Change in Wong-Baker FACES® Pain Rating Scale Score from Baseline to 12 weeks [Time frame: From time of intervention to 12 weeks post-intervention]
• Occurrence of infection during study period [Time frame: Up to 12 weeks post-intervention]
• Occurrence of further minor amputation during study period [Time frame: Up to 12 weeks post-intervention]
• Occurrence of major amputation during study period [Time frame: Up to 12 weeks post-intervention]
• Occurrence of death during study period [Time frame: Up to 12 weeks post-intervention]

Eligibility criteria

Inclusion criteria

• Age 21-100
• First or last toe ray amputation
• Adequate perfusion (either >50% stenosis on duplex ultrasound or undergone successful revascularization with <30% residual stenosis)

Exclusion criteria

• Amputations not at first or last toe
• Venous ulcers
• Heel ulcers
• Osteomyelitis
• Active Infection
• Patients on imunosuppressant
• Patients with known allergy to fish
• Patients unable to give informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Singapore · 2 centers

• Singapore General Hospital — Singapore
• Sengkang General Hospital — Singapore

Publications

• Ciprandi G, Kjartansson H, Grussu F, Baldursson BT, Frattaroli J, Urbani U, Zama M. Use of acellular intact fish skin grafts in treating acute paediatric wounds during the COVID-19 pandemic: a case series. J Wound Care. 2022 Oct 2;31(10):824-831. doi: 10.12968/jowc.2022.31.10.824. PMID 36240798
• Aerden D, Vanmierlo B, Denecker N, Brasseur L, Keymeulen B, Van den Brande P. Primary closure with a filleted hallux flap after transmetatarsal amputation of the big toe for osteomyelitis in the diabetic foot: a short series of four cases. Int J Low Extrem Wounds. 2012 Jun;11(2):80-4. doi: 10.1177/1534734612446640. Epub 2012 May 4. PMID 22561521
• Blume PA, Paragas LK, Sumpio BE, Attinger CE. Single-stage surgical treatment of noninfected diabetic foot ulcers. Plast Reconstr Surg. 2002 Feb;109(2):601-9. doi: 10.1097/00006534-200202000-00029. PMID 11818842
• Berceli SA, Brown JE, Irwin PB, Ozaki CK. Clinical outcomes after closed, staged, and open forefoot amputations. J Vasc Surg. 2006 Aug;44(2):347-351; discussion 352. doi: 10.1016/j.jvs.2006.04.043. PMID 16890866
• Zhang L, Weng T, Wu P, Li Q, Han C, Wang X. The Combined Use of Negative-Pressure Wound Therapy and Dermal Substitutes for Tissue Repair and Regeneration. Biomed Res Int. 2020 Dec 4;2020:8824737. doi: 10.1155/2020/8824737. eCollection 2020. PMID 33344649
• Normandin S, Safran T, Winocour S, Chu CK, Vorstenbosch J, Murphy AM, Davison PG. Negative Pressure Wound Therapy: Mechanism of Action and Clinical Applications. Semin Plast Surg. 2021 Aug;35(3):164-170. doi: 10.1055/s-0041-1731792. Epub 2021 Sep 10. PMID 34526864
• Riandini T, Pang D, Toh MPHS, Tan CS, Choong AMTL, Lo ZJ, Chandrasekar S, Tai ES, Tan KB, Venkataraman K. National Rates of Lower Extremity Amputation in People With and Without Diabetes in a Multi-Ethnic Asian Population: a Ten Year Study in Singapore. Eur J Vasc Endovasc Surg. 2022 Jan;63(1):147-155. doi: 10.1016/j.ejvs.2021.09.041. Epub 2021 Dec 14. PMID 34916107

Identifiers

NCT: NCT06832787 · 2024/2226

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗