related to urological interventions, thereby leading to better patient outcomes and reduced risk of antibiotic resistance. The platform provides a master protocol with inbuilt study control mechanisms for governance, ethics, common outcome measures and generic confounders. Study strategy and objectives DEEP-URO will initially focus on five index procedures, including radical prostatectomy, radical cystectomy, radical nephrectomy, transurethral resection of bladder tumours (TURBT), and transurethral resection of prostate (TURP). Study outcomes will be used to model personalised antibiotic prophylaxis protocols. The primary objective of DEEP-URO is to identify the limits of antibiotic prophylaxis de-escalation by comparing 30-day infection rates (deep tissue, skin, urinary tract, and sepsis) relative to contemporary intensive antibiotic prophylaxis protocols. Secondary objectives are to measure the need for additional surgical interventions to resolve an infection in 30 days, measure HRQoL (health-related quality of life) outcomes, and establish a separate cohort of microbiological samples of perineal swabs, rectal swabs, and urine for antimicrobial resistome research. “The traditional study designs used in medicine may not be the most efficient way to generate the necessary evidence due to the many technical variations in surgical procedures, patient factors, available antibiotics, and spatiotemporal variation of antimicrobial resistance.” Study cycles. To achieve study objectives, DEEP-URO will consist of cycles which include a cohort to establish baseline event rates (including AMR rates) followed by a randomised study testing efficacy of de-escalation as compared to standard of care. By following this cyclic structure, the study can be conducted in a rigorous and systematic way, with each cycle building upon the previous one to enhance the effectiveness of antibiotic prophylaxis de-escalation in the context of urological interventions. Cohort study. The aim is to identify the local incidence of surgical site infections, healthcare associated UTIs and sepsis, as well as antibiotic resistance rates. This information will inform the power calculations of the subsequent cluster randomised trial, which will evaluate the efficacy and safety of antibiotic prophylaxis de-escalation for a select intervention. Study clusters. Clusters will be created according to local antimicrobial resistance prevalence. The study platform will provide an information governance framework, data collection interface and data storage accessible for all sub-studies within DEEP-URO. A generic case report form (CRF) will be developed with subsections for the index procedure-
specific variables. The process of cycles to integrate a surveillance driven RCT approach is illustrated in Figure 6. Randomised trial. Run as a step-wedge design, the time a cluster switches from conventional extensive antibiotic prophylaxis arms to the limited antibiotic protocol will be randomised. Each cluster will focus on a specific urological intervention and will be conducted using a stepwise randomisation approach. The study will evaluate the effectiveness of de-escalation of antibiotic prophylaxis in reducing the incidence of infectious complications and antibiotic resistance while maintaining patient safety. Study sites and time plan DEEP-URO will be conducted at select hospitals with a well-established track record of successfully recruiting participants in previous portfolio studies, including GPIU and SERPENS. To ensure maximum recruitment, the national representatives should also identify centres in their respective countries that have experience and are skilled at leading capable participant recruitment. Based on our projections, we estimate that the first cycle of DEEP-URO will take approximately 30 months to complete. However, we anticipate that subsequent cycles will require less time to complete as the knowledge and expertise gained from each cycle accumulates. This will enable us to conduct future cycles more efficiently, potentially reducing the duration of each cycle and accelerating the overall progress of the study. Organisation The Deep-URO study is organised with principal investigators, a scientific working group and national lead investigators as shown in Textbox 1. Principal investigators: Dr. Zafer Tandoğdu (GB), Prof. Florian Wagenlehner (DE), Prof. Truls Erik Bjerklund Johansen (NO) Scientific working group: Dr. Lailla Schneidewind (DE), Dr. Jose Medina Polo (ES), Ms. Ana-Maria Tapia (ES), Dr. Jennifer Kranz (DE), Dr. Tommaso Cai (IT), Dr. Béla Köves (HU) National chief investigators: • Dr. Jose Medina Polo (ES) • Prof. Bhaskar Somani (GB) • Dr. Razvan Petca (RO) • Dr. Carlos Ferreira, and Dr. Tiago Oliveira (PT) • Dr. Ulanbek Zhanbyrbekuly (KZ) • Dr. Akis Afoko (UG) • Prof. Laila Schneidewind (DE) • Dr. Maxime Valee (FR) • Prof. Mathew Roberts (AU) • Prof. Jørgen Bjerggaard Jensen (DK) Database administrator: Dr. Adamos Hadjivasiliou (GB) Research fellow: Dr. Eva Falkensammer (AT)
Fig. 5: DEEP-URO study design
Fig. 6: Study platform with cycles of infective complications incidence connected to discrete trials to de-escalate antibiotic prophylaxis per procedure
We've already conducted a review of infection rates after urological procedures and are currently performing a systematic review of infective complications after robotic-assisted radical prostatectomy. We've scheduled regular video meetings under the leadership of Dr. Köves to ensure everyone is aligned and progressing towards our goals. Invitation We invite you to join us on this new journey. Our team values the contributions of all investigators, and we prioritise recognition through co-authorship and
acknowledgements. Together, we can make a historical change and find a solution to this growing problem. The DEEP-URO study will soon be open, and we need dedicated investigators and partners from strong urology centres who can commit themselves to perform complete DEEP-URO study cycles for a given procedure and help provide high-level evidence to support publication in high impact journals and inform urological guidelines. We need investigators who understand the trifecta of antimicrobial stewardship in urology, which can be summarised as "no infections, no resistance, and as little use of antibiotics as possible." Join us in this effort to tackle AMR in urology and make a real difference for patients around the world! References 1. Wagenlehner F, Tandogdu Z, Bartoletti R et al. The Global Prevalence of Infections in Urology Study: A long term, worldwide surveillance study on urological infections. Pathogens , 2016, 19;5(1), 10, doi:10.3390. PMID: 26797640 2. Naber KG, Scaeffer AJ, Heyns CF et al. Urogenital infections (Textbook 1182pp). International Consultation on Urological Diseases (ICUD) and European Association of Urology ISBN: 978-90-79754-41-0, Arnhem: 2010 3. Bjerklund Johansen TE, Wagenlehner FME, Matsumoto T, et al eds. Urogenital infections and inflammations. Berlin: GMS; 2017-.DOI: 10.5680/lhuii000032 4. F.M.E. Wagenlehner, E. van Oostrum, P. Tenke et al. Infective complications after prostate biopsy: Outcome of the Global Prevalence of Infections in Urology (GPIU) prostate biopsy study 2010 and 2011 – A prospective, multinational, multicentre prostate biopsy study. European Urology 2013; 63: 521-527. 5. Zafer Tandoğdu. Healthcare associated urinary tract infections in urology departments. Faculty of Medicine, University of Oslo. 2020. ISBN 978-82-8377-595-2 6. Tommaso Cai. Aspects of antimicrobial stewardship in urinary tract infections. Faculty of Medicine, University of Oslo. ISBN 978-82-8377-941-7
Textbox 1. Organisation of the DEEP-URO study
DEEP-URO was set in motion at EAU23 in Milan, where study protocols and objectives were discussed. Our scientific working group is committed to identifying the initial index procedures and developing electronic clinical record forms, building on previous work and leveraging IT solutions from the GPIU platform.
Fig. 4: Modular design of the dynamic Pan-European scientific platform
European Urology Today
April/May 2023
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