Trial of Negative-pressure Wound Therapy Use in Conflict-related Extremity Wounds

Study Overview
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Brief Summary
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There is a treatment method called negative-pressure wound therapy (NPWT) that is well established and used for the treatment of wounds. The method involves the application of a wound dressing through which a negative pressure is applied. Due to a plastic film overlaying the wound the risk of wound contamination is reduced. NPWT is considered to promote wound healing and prevent infection and has previously been used in the treatment of acute war associated wounds with satisfactory results. The aim of this study is to compare NPWT with conventional wound dressings in the treatment of war-associated extremity wounds and evaluate which method is more effective.

Detailed Description
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Trial locations: Médecins Sans Frontières/Doctors Without Borders (MSF) is one of the worlds leading independent organizations for medical humanitarian aid. MSF conducts an emergency trauma project in the Ministry of Health hospital in Ar Ramtha, Jordan, less than five kilometers from the border with Daraa governorate in Syria. A majority of patients within the project receive treatment for blast- and gunshot-related trauma wounds originating from the Syrian armed conflict. Within the project wound management has been difficult, often complicated by infection and antibiotic resistance. A need for wound therapy alternatives better than the conventional wound dressing method currently used has been identified. Emergency hospital in Erbil, Iraq is a trauma hospital. Patients originate from armed conflicts in Mosul and the Iraqi Kurdistan region. Background: Extremity wounds and fractures constitute the majority of war-associated traumatic injuries, both for civilians (Aboutanos & Baker 1997) and combatants (Owens et al. 2007). Conflict-related injuries often result in soft and boney tissue being contaminated with foreign material, generally leading to secondary infection (Fares et al. 2013; Covey et al. 2000). Negative-pressure wound therapy (NPWT) is widely used in the treatment of wounds and is considered to promote wound healing and prevent infectious complications. The technique involves the application of a wound dressing through which a negative pressure is applied. Any wound and tissue fluid is drawn away from the area and collected into a canister. The risk of wound contamination is reduced by a plastic film overlaying the wound. NPWT is supported for use in a range of surgical applications, including after or in between debridements as a bridge to definite closure of soft tissue wounds (Krug et al. 2011). The technique has previously been used in the treatment of acute conflict-related wounds with satisfactory results (Machen 2006; Peck et al. 2007; Leininger et al. 2006). Cochrane reviews of NPWT for the treatment of chronic wounds (Ubbink et al. 2008) and surgical wounds (Webster & Scuffham 2014) were inconclusive due to the lack of suitably powered, high-quality trials. A recent systematic review of randomized, controlled trials (RCTs) of NPWT for the treatment of acute and chronic wounds concluded there is a lack of evidence and that good RCTs are needed (Peinemann & Sauerland 2011). For the use in limb trauma, NPWT is considered suitable for complex soft tissue injuries (Bovill et al. 2008). NPWT appears to be an effective and safe adjunctive treatment of high-energy combat wounds but existing results are retrospective and lack follow-up (Hinck et al. 2010). The support of RCTs is needed to establish best treatment strategies. Summary of potential risks and benefits: Both treatment methods (NPWT and conventional dressings) are well established and used in Jordan for the treatment of acute and chronic wounds. As neither of the two treatment modalities are known to be better in terms of outcome neither patient group may be regarded as receiving preferential treatment. NPWT is generally considered a safe treatment method. Potential benefits are shortened healing time and fewer infectious complications. Potential risks are pain, mainly associated with dressing changes (Krasner 2002) and bleeding, predominantly minor bleeding from granulation tissue (Argenta, Louis Morykwas 1997). Conventional wound dressing has the potential benefit of being a safe treatment method used for many years. Since this method permits air into the wound there is a potential risk of contamination and the development of wound infection. Objectives: We aim to evaluate the efficacy and safety of NPWT in the treatment of traumatic extremity wounds in a context associated with a high level of contamination and infection. Design: A prospective, randomized, controlled trial comparing NPWT to conventional dressing methods in the treatment of conflict-related extremity wounds. Patients will continuously be included as they present at the emergency department of the hospital in Ar Ramtha. Information for patients and consent: Written and oral information in English and Arabic will be given to eligible participants. English versions of the participation information sheet and the consent form are provided as appendices to this document. Participants will be informed regarding their right to withdraw from the study and issues concerning confidentiality and the information sheet will remain with the participant. No incentives or inducements will be provided to any participant. Eligible concomitant therapies: Any signs of infection will be treated according to local standard protocols. Wounds in need of debridement will be debrided according to International Committee of the Red Cross (ICRC) war surgery protocols. Interventions: Patients randomly assigned to NPWT will receive treatment according to manufacturer treatment guidelines. Patients in the control group will be treated with conventional wound therapy according to local treatment protocols. In both groups dressing changes will be performed according to ICRC war surgery protocols.

Official Title
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A Prospective, Randomized, Controlled Trial of Negative-pressure Wound Therapy Use in Conflict-related Extremity Wounds (VACoCREW Trial)

Conditions
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Leg Injuries, Wounds, Gunshot, Arm Injuries, Wound Infection

Intervention / Treatment
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* Device: Vaccum Assisted Closure device
* Procedure: Conventional wound dressings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age with extremity blast- or gunshot-wound(s). In case of multiple wounds the extremity wound with the estimated largest area is selected. Exclusion Criteria: Wounds presenting >72 hours following initial trauma. Wounds that are considered ready for primary closure by suture or split-thickness skin graft.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Negative-pressure wound therapy<br>Vaccum Assisted Closure device. Patients will receive negative-pressure wound therapy according to manufacturer treatment guidelines. | Device: Vaccum Assisted Closure device<br>* Negative-pressure wound therapy<br>|
| Active Comparator: Standard<br>Patients will be treated with conventional wound dressings according to local treatment protocols. | Procedure: Conventional wound dressings<br>* Conventional wound dressings<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early wound closure | Wound closure, either by suture or split-thickness skin graft | Day five +-1 | 
| Cost-effectiveness comparing outcomes from NPWT and standard treatment | Costs from the health care provider's perspective will be used. Cost-effectiveness will be expressed in US dollars. | Days (between 1 and 50) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of wound healing | Days to wound closure by suture or split-thickness skin graft | Days (between 1 and 50) | 
| Wound infection | Verified by either positive culture or clinical sign of infection, defined as purulent discharge | Days (between 1 and 50) | 
| Time until wound is deemed no longer requiring professional care |  | Days (between 1 and 50) | 
| Time to discharge | Number of days to discharge | Days (between 1 and 50) | 
| Quality of life aspects | Quality of life aspects including noise generated by the NPWT pump, movement impairment, skin irritation, odour, sleep quality, discomfort during dressing changes and pain | Days five and eight | 
| Full wound healing at follow-up | Full epithelialization | Day 30 following wound closure | 
| Septicaemia | Septicaemia verified by positive blood culture | Days (between 1 and 50) | 
| Mortality | Death | Days (between 1 and 50) | 
| Wound size ratio day fourteen | Wound size day fourteen divided by size day zero, i.e. wound healing rate after fourteen days | Day 14 | 
| Number of surgeries |  | Days (between 1 and 50) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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war, wounds, negative-pressure wound therapy, conflict, gunshot wound, blast injuries, civilian