Fluid Lavage of Open Wounds (FLOW): design and rationale for a large, multicenter collaborative 2 × 3 factorial trial of irrigating pressures and solutions in patients with open fractures

Abstract

BackgroundOpen fractures frequently result in serious complications for patients, including infections, wound healing problems, and failure of fracture healing, many of which necessitate subsequent operations. One of the most important steps in the initial management of open fractures is a thorough wound irrigation and debridement to remove any contaminants. There is, however, currently no consensus regarding the optimal approach to irrigating open fracture wounds during the initial operative procedure. The selection of both the type of irrigating fluid and the pressure of fluid delivery remain controversial. The primary objective of this study is to investigate the effects of irrigation solutions (soap vs. normal saline) and pressure (low vs. high; gravity flow vs. high; low vs. gravity flow) on re-operation within one year among patients with open fractures.Methods/DesignThe FLOW study is a multi-center, randomized controlled trial using a 2 × 3 factorial design. Surgeons at clinical sites in North America, Europe, Australia, and Asia will recruit 2 280 patients who will be centrally randomized into one of the 6 treatment arms (soap + low pressure; soap + gravity flow pressure; soap + high pressure; saline + low pressure; saline + gravity flow pressure; saline + high pressure). The primary outcome of the study is re-operation to promote wound or bone healing, or to treat an infection. This composite endpoint of re-operation includes a narrow spectrum of patient-important procedures: irrigation and debridement for infected wound, revision and closure for wound dehiscence, wound coverage procedures for infected or necrotic wound, bone grafts or implant exchange procedures for established nonunion in patients with postoperative fracture gaps less than 1 cm, intramedullary nail dynamizations in the operating room, and fasciotomies for compartment syndrome. Patients, outcome adjudicators, and data analysts will be blinded. We will compare rates of re-operation at 12 months across soap vs. saline, low pressure vs. high pressure, gravity flow pressure vs. high pressure, and low pressure vs. gravity flow pressure. We will measure function and quality of life with the Short Form-12 (SF-12) and the EuroQol-5 Dimensions (EQ-5D) at baseline, 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 12 months after initial surgical management, and measure patients' illness beliefs with the Somatic Pre-Occupation and Coping (SPOC) questionnaire at 1 and 6 weeks. We will also compare non-operatively managed infections, wound healing, and fracture healing problems at 12 months after initial surgery.DiscussionThis study represents a major international effort to identify a simple and easily applicable strategy for emergency wound management. The importance of the question and the potential to identify a low cost treatment strategy argues strongly for global participation, especially in low and middle income countries such as India and China where disability from traumatic injuries is substantial.Trial RegistrationThis trial is regist...

Predictors of nonunion and reoperation in patients with fractures of the tibia: an observational study

“…Although the presence of an open fracture was not a significant covariate in the multiple logistic regression model, open fractures are known prognostic factors for complications following fracture fixation [31-35] and this characteristic demonstrated a significant association to the incidence of both nonunion and reoperation in the univariate models, suggesting a possible study power issue. Our findings suggest a trend towards increased reoperations with transverse fractures compared to oblique or spiral fractures and is consistent with previous reports of their characteristic association to high-impact injuries and the need for reoperation to achieve bony union in such cases [11,25].…”

Are large clinical trials in orthopaedic trauma justified?

“…Had this been our intent, erroneous treatment recommendations would have been made. In contrast, the sample size for the FLOW definitive trial was based on a sample size calculation, where we carefully considered realistic a priori event rates and corresponding reductions in relative risks between the treatment groups based upon the previous literature and the opinion of multiple experts [ 4 ].…”

“…The FLOW pilot study included 89 patients at nine clinical sites in Canada and the United States. The results of the FLOW pilot study (ClinicalTrials.gov number, NCT01069315) informed the development of the FLOW definitive trial (ClinicalTrials.gov number, NCT00788398), which was a multi-center, blinded, randomized controlled trial, using a 2 × 3 factorial design which evaluated irrigation solution (soap vs. normal saline) and irrigation pressure (very low vs. low vs. high) in patients with open fracture wounds [ 4 ]. The FLOW definitive trial included 2447 patients across 41 clinical sites in the United States, Canada, Australia, Norway, and India [ 5 ].…”

Nonunion in Patients with Tibial Shaft Fractures: Is Early Physical Status Associated with Fracture Healing?

“…This study was an observational cohort study nested within two multicenter, randomized controlled trials, including the Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Shaft Fractures (SPRINT) and the Fluid Lavage of Open Wounds (FLOW) trial [17][18].…”

“…The full SPRINT study protocol and study results have been previously published [17][18]. The trial received approval from the human subjects committee at each participating site (REB #99-077-Research Ethics Board/Institutional Review Boards).…”