A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan
Authors: O’Hara Nathan N. , Heels-Ansdell Diane , Bzovsky Sofia , Dodds Shannon , Thabane Lehana , Bhandari Mohit , Guyatt Gordon , Devereaux P. J. , Slobogean Gerard P. , Sprague Sheila ,   on behalf of the PREP-IT Investigators, Harris Anthony D. , Mullins C. Daniel , Wells Jeffrey , Wood Amber , Della Rocca Gregory J. , Hebden Joan , Jeray Kyle J. , Marchand Lucas S. , O’Hara Lyndsay M. , Zura Robert , Lee Christopher , Patterson Joseph , Gardner Michael J. , Blasman Jenna , Davies Jonah , Liang Stephen , Taljaard Monica , Thabane Lehana , Marvel Debra , Palmer Jana , Friedrich Jeff , Grissom Frances , Gitajn I. Leah , Morshed Saam , O’Toole Robert V. , Petrisor Bradley A. , Mossuto Franca , Joshi Manjari G. , D’Alleyrand Jean-Claude , Fowler Justin , Rivera Jessica , Talbot Max , Sprague Sheila , Pogorzelski David , Li Silvia , Rojas Alejandra , Del Fabbro Gina , Szasz Olivia Paige , McKay Paula , Minea Alexandra , Murphy Kevin , Howe Andrea , Demyanovich Haley K. , Medeiros Michelle , Polk Genevieve , Kettering Eric , Mahal Nirmen , Eglseder Andrew , Johnson Aaron , Langhammer Christopher , Lebrun Christopher , Nascone Jason , Pensy Raymond , Pollak Andrew , Sciadini Marcus , Degani Yasmin , Phipps Heather , Hempen Eric , Johal Herman , Ristevski Bill , Williams Dale , Denkers Matthew , Rajaratnam Krishan , Al-Asiri Jamal , Gallant Jodi , Pusztai Kaitlyn , MacRae Sarah , Renaud Sara , Adams John D. , Beckish Michael L. , Bray Christopher C. , Brown Timothy R. , Cross Andrew W. , Dew Timothy , Faucher Gregory K. , Gurich Richard W. , Lazarus David E. , Millon S. John , Palmer M. Jason , Porter Scott E. , Schaller Thomas M. , Sridhar Michael S. , Sanders John L. , Rudisill L. Edwin , Altman Kyle M. , Quirion Julia C. , Loeffler Markus F. , Pichiotino Erin R. , Cole Austin A. , Maltz Ethan J. , Parker Wesley , Ramsey T. Bennett , Burnikel Alex , Colello Michael , Stewart Russell , Wise Jeremy , Moody M. Christian , Anderson Matthew , Eskew Joshua , Judkins Benjamin , Miller James M. , Tanner Stephanie L. , Snider Rebecca G. , Bray Emily , Abbott Harper , Natoli Roman M. , McKinley Todd O. , Virkus Walter W. , Sorkin Anthony T. , Szatkowski Jan P. , Mullis Brian H. , Jang Yohan , Lopas Luke A. , Hill Lauren C. , Fentz Courteney L. , Diaz Maricela M. , Brown Krista , Garst Katelyn M. , Denari Emma W. , Osborn Patrick , Pierrie Sarah , Herrera Maria , Miclau Theodore , Marmor Meir , Matityahu Amir , McClellan R. Trigg , Shearer David , Toogood Paul , Ding Anthony , Murali Jothi , El Naga Ashraf , Tangtiphaiboontana Jennifer , Belaye Tigist , Berhaneselase Eleni , Pokhvashchev Dmitry , Obremskey William T. , Jahangir Amir Alex , Sethi Manish , Boyce Robert , Stinner Daniel J. , Mitchell Phillip , Trochez Karen , Rodriguez Elsa , Pritchett Charles , Hogan Natalie , Moreno A. Fidel , Hagen Jennifer E. , Patrick Matthew , Vlasak Richard , Krupko Thomas , Talerico Michael , Horodyski Marybeth , Koenig Chris , Pazik Marissa , Lossada-Soto Elizabeth , Gary Joshua L. , Warner Stephen J. , Munz John W. , Choo Andrew M. , Achor Timothy S. , Chip Routt Milton L. , Kutzler Michael , Boutte Sterling , Warth Ryan J. , Prayson Michael , Venkatarayappa Indresh , Horne Brandon , Jerele Jennifer , Clark Linda , Boulton Christina , Lowe Jason , Ruth John T. , Askam Brad , Seach Andrea , Cruz Alejandro , Featherston Breanna , Carlson Robin , Romero Iliana , Zarif Isaac , Dehghan Niloofar , McKee Michael , Sietsema Debra L. , Williams Alyse , Dykes Tayler , Guerra-Farfan Ernesto , Tomas-Hernandez Jordi , Teixidor-Serra Jordi , Molero-Garcia Vicente , Selga-Marsa Jordi , Porcel-Vazquez Juan Antonio , Andres-Peiro Jose Vicente , Minguell-Monyart Joan , Nuñez-Camarena Jorge , del Mar Villar-Casares Maria , Mestre-Torres Jaume , Lalueza-Broto Pilar , Moreira-Borim Felipe , Garcia-Sanchez Yaiza , Marcano-Fernández Francesc , Martínez-Carreres Laia , Martí-Garín David , Serrano-Sanz Jorge , Sánchez-Fernández Joel , Sanz-Molero Matsuyama , Carballo Alejandro , Pelfort Xavier , Acerboni-Flores Francesc , Alavedra-Massana Anna , Anglada-Torres Neus , Berenguer Alexandre , Cámara-Cabrera Jaume , Caparros-García Ariadna , Fillat-Gomà Ferran , Fuentes-López Ruben , Garcia-Rodriguez Ramona , Gimeno-Calavia Nuria , Martínez-Álvarez Marta , Martínez-Grau Patricia , Pellejero-García Raúl , Ràfols-Perramon Ona , Peñalver Juan Manuel , Domènech Mònica Salomó , Soler-Cano Albert , Velasco-Barrera Aldo , Yela-Verdú Christian , Bueno-Ruiz Mercedes , Sánchez-Palomino Estrella , Andriola Vito , Molina-Corbacho Matilde , Maldonado-Sotoca Yeray , Gasset-Teixidor Alfons , Blasco-Moreu Jorge , Fernández-Poch Núria , Rodoreda-Puigdemasa Josep , Verdaguer-Figuerola Arnau , Cueva-Sevieri Heber Enrique , Garcia-Gimenez Santiago , Viskontas Darius G. , Apostle Kelly L. , Boyer Dory S. , Moola Farhad O. , Perey Bertrand H. , Stone Trevor B. , Lemke H. Michael , Spicer Ella , Payne Kyrsten , Hymes Robert A. , Schwartzbach Cary C. , Schulman Jeff E. , Malekzadeh A. Stephen , Holzman Michael A. , Gaski Greg E. , Wills Jonathan , Ahn James S. , Das Sharmistha , English Antoinisha D. , Cuff Jaslynn A. N. , Pilson Holly , Carroll Eben A. , Halvorson Jason J. , Babcock Sharon , Goodman J. Brett , Holden Martha B. , Williams Wendy , Hill Taylor , Brotherton Ariel , Romeo Nicholas M. , Vallier Heather A. , Fraifogl Joanne , Vergon Anna , Higgins Thomas F. , Haller Justin M. , Rothberg David L. , Neese Ashley , Olsen Zachary M. , McGowan Abby V. , Hill Sophia , Dauk Morgan K. , Bergin Patrick F. , Russell George V. , Graves Matthew L. , Morellato John , McGee Sheketha L. , Bhanat Eldrin L. , Yener Ugur , Khanna Rajinder , Nehete Priyanka , Potter David , VanDemark Robert , Atkins Kristi , Coe Marcus , Dwyer Kevin , Mullin Devin S. , Chockbengboun Theresa A. , Phelps Kevin , Bosse Michael , Karunakar Madhav , Kempton Laurence , Sims Stephen , Hsu Joseph , Seymour Rachel , Churchill Christine , Mayfield Ada , Sweeney Juliette , Jaeblon Todd , Beer Robert , Bauer Brent , Meredith Sean , Benzel Caroline , Domes Christopher M. , Reilly Rachel M. , Paniagua Ariana , Dupree Ja Nell , Weaver Michael J. , von Keudell Arvind G. , Sagona Abigail E. , Mehta Samir , Donegan Derek , Horan Annamarie , Dooley Mary , Heng Marilyn , Harris Mitchel B. , Lhowe David W. , Esposito John G. , Alnasser Ahmad , Shannon Steven F. , Scott Alesha N. , Clinch Bobbi , Weber Becky , Beltran Michael J. , Archdeacon Michael T. , Sagi Henry Claude , Wyrick John D. , Le Theodore Toan , Laughlin Richard T. , Thomson Cameron G. , Hasselfeld Kimberly , Lin Carol A. , Vrahas Mark S. , Moon Charles N. , Little Milton T. , Marecek Geoffrey S. , Dubuclet Denice M. , Scolaro John A. , Learned James R. , Lim Philip K. , Demas Susan , Amirhekmat Arya , Dela Cruz Yan Marco 
Published: September 2022

Background

Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020.

Methods and design

The Aqueous-PREP trial is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. Each participating cluster is randomly assigned in a 1:1 ratio to provide 1 of the 2 study interventions on all eligible patients during a study period. The intervention periods are 2 months in length. After completing a 2-month period, the participating cluster crosses over to the alternative intervention. We plan to enroll a minimum of 1540 patients at 14 sites.

Results

The primary outcome is surgical site infection guided by the Centers for Disease Control and Prevention’s National Healthcare Safety Network reporting criteria (2017). All participants’ surgical site infection surveillance period will end 30 days after definitive fracture management surgery for superficial infections and 90 days after definitive fracture management surgery for deep incisional or organ/space infections [1]. The secondary outcome is an unplanned fracture-related reoperation within 12 months of the fracture.

Conclusion

This manuscript serves as the formal statistical analysis plan (version 1.0) for the Aqueous-PREP trial. The statistical analysis plan was completed on February 28, 2022.