Effectiveness of Iodophor vs Chlorhexidine Solutions for Surgical Site Infections and Unplanned Reoperations for Patients Who Underwent Fracture Repair
Authors: Gerard P. Slobogean, Sheila Sprague, Jeffrey Wells, Mohit Bhandari, Jean-Claude D'Alleyrand, Anthony D. Harris, Daniel C. Mullins, Lehana Thabane, Amber Wood, Gregory J. Della Rocca, Joan Hebden, Kyle J. Jeray, Lucas Marchand, Lyndsay M. O'Hara, Robert Zura, Michael J. Gardner, Jenna Blasman, Jonah Davies, Stephen Liang, Monica Taljaard, PJ Devereaux, Gordon Guyatt, Debra Marvel, Jana Palmer, Jeff Friedrich, Nathan N. O'Hara, Ms. Frances Grissom, I. Leah Gitajn, Saam Morshed, Robert V. O'Toole, Brad A. Petrisor, Megan Camara, Franca Mossuto, Manjari G. Joshi, Justin Fowler, Jessica Rivera, Max Talbot, Shannon Dodds, Alisha Garibaldi, Silvia Li, Uyen Nguyen, David Pogorzelski, Alejandra Rojas, Taryn Scott, Gina Del Fabbro, Olivia P. Szasz, Diane Heels-Ansdell, Paula McKay, Andrea Howe, Joshua Rudnicki, Haley Demyanovich, Kelly Little, Eric Kettering, Diamond Hale, Andrew Eglseder, Aaron Johnson, Christopher Langhammer, Christopher Lebrun, Theodore Mandon, Jason Nascone, Ebrahim Paryavi, Raymond Pensy, Andrew Pollak, Marcus Sciadini, Yasmin Degano, Haley K. Demyanovich, Katherine Joseph, Herman Johal, Bill Ristevski, Dale Williams, Matthew Denkers, Krishan Rajaratnam, Jamal Al-Asiri, Jordan Leonard, Francesc A. Marcano-Fernández, Jodi Gallant, Federico Persico, Marko Gjorgjievski, Roman N. Natoli, Greg E. Gaski, Todd O. McKinley, Walter W. Virkus, Anthony T. Sorkin, Jan P. Szatkowski, Joseph R. Baele, Brian H. Mullis, Lauren C. Hill, Andrea Hudgins, Patrick Osborn, Sarah Pierrie, Eric Martinez, Joseph Kimmel, John D. Adams, Michael L. Beckish, Christopher C. Bray, Timothy R. Brown, Andrew W. Cross, Timothy Dew, Gregory K. Faucher, Richard W. Gurich, David E. Lazarus, S. John Millon, M. Jason Palmer, Scott E. Porter, Thomas M. Schaller, Michael S. Sridhar, John L. Sanders, L. Edwin Rudisill, Michael J. Garitty, Andrew S. Poole, Michael L. Sims, Clark M. Walker, Robert M. Carlisle, Erin Adams-Hofer, Brandon S. Huggins, Michael D Hunter, William A. Marshall, Shea Bielby Ray, Cory D. Smith, Kyle M. Altman, Julia C. Bedard, Markus F. Loeffler, Erin R. Pichiotino, Austin A. Cole, Ethan J. Maltz, Wesley Parker, T. Bennett Ramsey, Alex Burnikel, Michael Colello, Russel Stewart, Jeremy Wise, Stephanie L. Tanner, Rebecca G. Snider, Christine E. Townsend, Kayla H. Pham, Abigail Martin, Emily Robertson, Utku Kandemir, Meir Mormor, Amir Matityahu, R. Trigg McClellan, Eric Meinberg, Theodore Miclau, David Shearer, Paul Toogood, Anthony Ding, Erin Donohue, Tigist Belaye, Eleni Berhaneselase, Alexandra Paul, Kartik Garg, Joshua L. Gary, Stephanie J. Warner, John W. Munz, Andrew M. Choo, Timothy S. Schor, Milton L. "Chip" Routt, Mayank Rao, Guillermo Pechero, Adam Miller, Jennifer E. Hagen, Matthew Patrick, Kalia Sadasivan, Chris Koenig, Daniel Bailey, Daniel Wentworth, Chi Van, Justin Schwartz, Clifford B. Jones, J. Tracy Watson, Michael McKee, Niloofar Dehghan, Ammar Karim, Michael Talerico, Debra L. Sietsema, Alyse Williams, Tayler Dykes, William T. Obremsky, Amir A. Jahangir, Manish Sethi, Robert Boyce, Daniel J. Stinner, Karen Trochez, Andres Rodriguez, Vamshi Gajari, Olivia Knoll, Charles Pritchett, Christina Boulton, Jason Lowe, Jason Wild, John T. Ruth, Michel Taylor, Andrea Seach, Sabina Saeed, Hunter Culbert, Alejandro Cruz, Thomas Knapp, Colin Hurkett, Maya Lowney, Michael Prayson, Indresh Venkatarayappa, Brandon Horne, Jennifer Jerele, Linda Clark, Kammie Snure, Mara L. Schenker, Michael Maceroli, William Reisman, Clifton Meals, Thomas Moore, Brent Wise, Diane Payne, Christopher Sadlack, Erika Ortega, Nicholas M. Romeo, Heather A. Vallier, Mary A. Breslin, Joanne Fraifogl, Eleanor S. Wilson, Leanne K. Wadenpfuhl, Darius G. Viskontas, Kelly L. Apostle, Dory S. Boyer, Farhas O. Moola, Bertrand H. Perey, Trevor B. Stone, H. Michael Lemke, Mauri Zomar, Ella Spicer, Chen "Brenda" Fan, Krysten Payne, Kevin Phelps, Michael Bosse, Madhav Karunakar, Laurence Kempton, Stephen Sims, Joseph Hsu, Rachel Seymour, Christine Churchill, Claire Bartel, Robert Miles Mayberry, Mary Brownrigg, Kanesha Whitworth Brown, Ada Mayfield, Robert A. Hymes, Cary C. Schwartzbach, Jeff E. Schulman, A. Stephen Malekzadeh, Michael A. Holzman, Lolita Ramsey, James S. Ahn, Farhanaz Panjshiri, Sharon M. Haaser, Jaslynn A. N. Cuff, Holly Pilson, Eben A. Carroll, Jason J. Halvorson, Sharon Babcock, J. Brett Goodman, Martha B. Holden, Debra Bullard, Wendy Williams, Thomas F. Higgins, Justin M. Haller, David L. Rothberg, Ashley Neese, Mark Russell, Marcus Coe, Kevin Dwyer, Devin Mullin, Cliff Reilly, Peter DePalo, Marilyn Heng, Mitchel B. Harris, R. Malcolm Smith, David W. Lhowe, John G. Esposito, Mira Bansal, Patrick F. Bergin, George V. Russell, Matthew L. Graves, John Morellato, LaRita C. Jones, Heather K. Champion, Leslie N. Johnson, Susan Q. Allbritton, Samir Mehta, Derek Donehan, Jaimo Ahn, Annamarie Horan, Kelly Clark, Mary Dooley, Justina Toma, Ashley Kuczinski, David Potter, Robert VanDemark, Branden Pfaff, Michael J. Weaver, Arvind G. von Keudell, Michael F. McTague, Elizabeth M. Allen, Todd Jaeblon, Robert Beer, Mark J. Gage, Rachel M. Reilly, Cindy Sparrow, Gerard P. Slobogean, Sheila Sprague, Jeffrey Wells, Mohit Bhandari, Alejandra Rojas, Alisha Garibaldi, Amber Wood, Andrea Howe, Anthony D. Harris, Bradley A. Petrisor, Daniel C. Mullins, David Pogorzelski, Debra Marvel, Diane Heels-Ansdell, Franca Mossuto, Frances Grissom, Gina Del Fabbro, Gordon H. Guyatt, Gregory J. Della Rocca, Haley K. Demyanovich, I. Leah Gitajn, Jana Palmer, Jean-Claude D’Alleyrand, Jeff Friedrich, Jessica Rivera, Joan Hebden, Joshua Rudnicki, Justin Fowler, Kyle J. Jeray, Lehana Thabane, Lucas Marchand, Lyndsay M. O’Hara, Manjari G. Joshi, Max Talbot, Megan Camara, Olivia Paige Szasz, Nathan N. O’Hara, Paula McKay, P. J. Devereaux, Robert V. O’Toole, Robert Zura, Saam Morshed, Shannon Dodds, Silvia Li, Stephanie L. Tanner, Taryn Scott, Uyen Nguyen
Journal: JAMA Network Open (2020)

The risk of developing a surgical site infection after extremity fracture repair is nearly 5 times greater than in most elective orthopedic surgical procedures. For all surgical procedures, it is standard practice to prepare the operative site with an antiseptic solution; however, there is limited evidence to guide the choice of solution used for orthopedic fracture repair.To compare the effectiveness of iodophor vs chlorhexidine solutions to reduce surgical site infections and unplanned fracture-related reoperations for patients who underwent fracture repair.The PREP-IT (Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma) master protocol will be followed to conduct 2 multicenter pragmatic cluster randomized crossover trials, Aqueous-PREP (Pragmatic Randomized Trial Evaluating Pre-Operative Aqueous Antiseptic Skin Solution in Open Fractures) and PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities). The Aqueous-PREP trial will compare 4% aqueous chlorhexidine vs 10% povidone-iodine for patients with open extremity fractures. The PREPARE trial will compare 2% chlorhexidine in 70% isopropyl alcohol vs 0.7% iodine povacrylex in 74% isopropyl alcohol for patients with open extremity fractures and patients with closed lower extremity or pelvic fractures. Both trials will share key aspects of study design and trial infrastructure. The studies will follow a pragmatic cluster randomized crossover design with alternating treatment periods of approximately 2 months. The primary outcome will be surgical site infection and the secondary outcome will be unplanned fracture-related reoperations within 12 months. The Aqueous-PREP trial will enroll a minimum of 1540 patients with open extremity fractures from at least 12 hospitals; PREPARE will enroll a minimum of 1540 patients with open extremity fractures and 6280 patients with closed lower extremity and pelvic fractures from at least 18 hospitals. The primary analyses will adhere to the intention-to-treat principle and account for potential between-cluster and between-period variability. The patient-centered design, implementation, and dissemination of results are guided by a multidisciplinary team that includes 3 patients and other relevant stakeholders.The PREP-IT master protocol increases efficiency through shared trial infrastructure and study design components. Because prophylactic skin antisepsis is used prior to all surgical procedures and the application, cost, and availability of all study solutions are similar, the results of the PREP-IT trials are poised to inform clinical guidelines and bring about an immediate change in clinical practice.ClinicalTrials.gov Identifiers: NCT03385304 and NCT03523962.