A Randomised Controlled Trial of standard care wound management versus negative pressure wound therapy in the treatment of adult patients with an open fracture of the lower limb HTA 10/57/20 Professor Matthew Costa Warwick Orthopaedics University of Warwick

Background In severe, high-energy fractures of the lower limb, infection rates of 27% are reported Pollak AN, Jones AL, Castillo RC, Bosse MJ, MacKenzie EJ. The relationship between time to surgical debridement and incidence of infection after open high-energy lower extremity trauma. J Bone Joint Surg Am 2010;92(1):7-15. Huge health care cost associated - £163,000 if the limb can be salvaged and £500,000+ if amputation is required MacKenzie EJ, Jones AS, Bosse MJ, Castillo RC, Pollak AN, Webb LX, et al. Health-care costs associated with amputation or reconstruction of a limb-threatening injury. J Bone Joint Surg Am 2007;89(8):

Background A recent consensus paper recommended that NPWT “should be considered when primary closure is not possible” but acknowledged that the evidence base to support this statement was very limited Runkel N, Krug E, Berg L, Lee C, Hudson D, Birke-Sorensen H, et al. Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus. Injury 2011;42 Suppl 1:S1-12.

So the trial.... VS

NPWT NPWT dressing uses an ‘open-cell’, solid foam which is laid onto the wound followed by an adherent, sealed dressing. A hole is cut in the layer over the foam and a sealed tube is used to connect the foam to a pump which creates a partial vacuum over the wound.

Design A feasibility phase –to qualitatively assess patients experience of giving consent –and to determine the number of eligible and recruited patients in 5 trauma centres over 6 months

Design A multi-centre, randomised, controlled trial A minimum of 460 patients 18 UK trauma centres 27 month recruitment period Standard-of-care vs. NPWT 1:1 web-based randomisation stratified by trial centre and Gustilo and Anderson grade

WOLLF Centres Birmingham  Newcastle   Oxford  Bristol  Coventry  Nottingham  Cambridge  Poole  Berkshire  Leicester  Brighton  Norwich Plymouth  Southampton 

Timelines Main phase of recruitment complete Sep 2015 Follow up complete Sep 2016 Final report due to HTA – Feb 2017

Inclusion Criteria: Aged 16 years or over Present to the trial hospital within 72 hours of injury Have an open fracture of the lower limb – graded as Gustilo and Anderson 2, 3 or 3+ with vascular injury requiring surgical intervention Exclusion Criteria: Contra-indications to anaesthesia Unable to adhere to trial procedures or complete questionnaires

Outcome Measures Primary –Disability Rating Index (DRI) E.g. Without difficulty Not at all Dressing (without help) Out-door walks Climbing stairs

Outcome Measures Contd. Secondary: –Rate of deep infection (radiographs, photographs, medical interventions) –Quality of life (SF-12, EQ-5D) –Cost effectiveness evaluation (resource use) –Complications

Data Collection Baseline6 weeks 3 months 6 months 9 months 12 months Radiographs XXX Photographs X DRI, SF-12 XXXXX Complications XXXXX Health Economics XXXXX

Recruitment

Team at Brighton (RSC) Principal Investigator Mr Benedict Rogers Research Associates Carrie West, Laura Ortiz-Ruiz De Gordoa Centre Target 1 patient per month

Patient admitted to hospital with open lower limb fracture Standard investigations including x-rays Check against inclusion and exclusion criteria Excluded Ensure RA is made aware of all patients with an open limb fracture fracture – this means ED staff will need to notify the RA of potential patients Ensure lateral and PA x-rays are taken Review imaging and confirm eligibility of patient in conjunction with RA Attend trauma meetings Review images with PI/delegated surgeon and confirm eligibility of patient If ineligible add patient details to screening log If eligible proceed to gain agreement for randomisation from personal or professional consultee or consent from patient PI Responsibilities RA Responsibilities Screening Gain agreement or consent

Seek consent or agreement Decline consent/agreement If necessary, answer any questions the patient/consultee may have about the trial Inform surgeons they will need to give agreement to randomisation Answer questions about the trial If unwilling to give agreement or consent, add patient details to screening log If willing patient will sign the prospective consent form If agreement is sought, add the consultees name to the patient entry form and perform randomisation and when informed by the clinical team that the patient may be approached seek consent to follow-up RA ResponsibilitiesPI Responsibilities Consent or Agreement?

1:1 online randomisation NPWT (230)Standard dressing (230) Ensure surgeon knows to grade most severe wound Ensure all theatre staff are aware of WOLLF Ensure that the RA can attend theatre and if not ensure theatre staff are trained in randomising Ensure surgeons give patients the allocated treatment to the most severe wound Take WOLLF pump to theatre One login and password per centre Tell surgeon treatment allocation Complete entry form and return to coordinating centre All randomisers must be GCP trained RA/Randomiser Responsibilities PI Responsibilities Surgery & Randomisation Assessment of GA grading of most severe wound Excluded

Seek written consent to follow-up Decline consent If necessary, answer any questions the patient may have about the trial When informed by the clinical team that the patient may be approached, give them the Patient Information Sheet Answer patient’s questions about the trial If unwilling, add patient details to screening log and complete a withdrawal form If willing, sign consent form and complete baseline CRFs in booklet Complete CRF booklet RA Responsibilities PI Responsibilities Consent to Follow-up

3/12, 6/12 & 9/12 postal questionnaires: DRI, SF-12, EQ-5D, complications and economics 12/12 questionnaire & radiographs 6/52 routine clinic: complications, radiographs & photograph Arrange follow-up appointment at approximately 6-weeks including repeat x-rays Ensure RA is aware of the date of the ‘6 week’ appointment Ensure that 12 month follow-up appointment is booked including repeat x-rays Complete ‘6 week’ form Take 6 week photograph Return CRF booklet together with baseline and ‘6 week’ images on disc to the WOLLF trial office Send 12 month post injury x-rays to the WOLLF trial office RA Responsibilities PI Responsibilities Follow-up

Challenges Gaining agreement/consent Ensuring all patients are screened and all eligible patients are randomised Operation note completion Implementing a system to ensure RA is made aware of 6 week and 12 months visits Randomisation Supply of pump and dressings

The Outcome... An evidence-based change in clinical practice for an important group of patients.

Questions ?

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