Introduction of Mycotic Prophylaxis At Cystectomy Trial.

Официальное название

IMPACT - the Introduction of Mycotic Prophylaxis At Cystectomy Trial. Perioperative Mycotic Prophylaxis to Reduce Postoperative Complications Following Cystectomy - a Double-blinded, Placebo-controlled, Randomized Trial

Обзор

This study aims to introduce a perioperative antifungal prophylaxis for patients undergoing cystectomy: surgically removal of the urinary bladder with construction of a urinary diversion. We wish to investigate the effect of antifungal prophylaxis on complications after the operation.

Подробное описание

Cystectomy with construction of a urinary diversion, is a major cancer surgery and one of the most complex surgeries in the urological specialty. After cystectomy, the most commonly performed urinary diversion is an ileal conduit, where a section of the terminal ileum is shunted out and connected to the upper urinary tract and a stoma is created. During this procedure, the abdominal cavity is exposed to bacteria and fungus from the ileum. Besides the perioperative contamination, micro-leakage in relation to the anastomosis is suspected to contribute to a local infectious response that may result in postoperative complications as ileal paralysis. Paralytic ileus is a serious complication that affects many patients after cystectomy, resulting in a prolonged length of stay, low quality of life postoperatively, and increased risk of complications such as aspiration, pneumonia, wound rupture, deep venous thrombosis, undernourishment and infections.

Current guidelines support the use of perioperative antibiotics targeting gram-negative and gram-positive bacteria, typically administered as broad-spectrum medicine such as piperacillin/tazobactam or cephalosporins. Regarding fungal infections, emerging data show that 48% of the patients undergoing RC have candida albicans in samples from the terminal ileum. Also, it is well known that fungal infections are highly prevalent in patients undergoing gastrointestinal surgery where it is associated with a high risk of mortality.

Small retrospective studies suggest that the addition of antifungal medicine to perioperative antibiotics can reduce the risk of bowel- and infectious complications after abdominal surgery.

The compelling theoretical and clinical rationale for addition of antifungal prophylaxis to standard-of-care antibiotic prophylaxis for patients undergoing radical cystectomy provides the basis for initiation of a randomized clinical trial representing the highest level of evidence.

Вмешательства

• Препарат Fluconazole
  400 mg inravenous Fluconazole, single dose 200 ml
• Препарат Isotonic saline solution
  Intravenous saline solution, single dose 200 ml

Первичные конечные точки

• Postoperative complications [Срок оценки: 90 days from surgery]

Вторичные конечные точки (7)

• Days Alive and Out of Hospital (DAOH) [Срок оценки: 90 days from surgery]
• Time to gastrointestinal function [Срок оценки: Postoperatively within 90 days]
• Nasogastric tube placement [Срок оценки: Postoperatively within 90 days]
• Length of stay (LOS) [Срок оценки: 90 days from surgery]
• Readmission rate [Срок оценки: 90 days after surgery]
• Quality of life (QoL): EORTC QLQ-C30 [Срок оценки: Before operation and 90 days after surgery]
• Quality of Life(QOL): EORTC QLQ-BLM30 [Срок оценки: Before operation and 90 days after]

Критерии участия

Критерии включения

• Patients 18 years and older
• Willingness to participate in the study and the ability to understand and sign an informed consent
• Indication for performing cystectomy
• The urinary diversion is limited to the ileal conduit

Критерии исключения

• Patients with contraindications to Fluconazole. This includes allergies and treatment with non-pausable medication that in combination is contraindicated
• Patients in active treatment for mycotic infections

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Дания · 1 центр

• Department of Urology, Rigshospitalet — Copenhagen

Публикации

• Maibom SL, Roder MA, Poulsen AM, Thind PO, Salling ML, Salling LN, Kehlet H, Brasso K, Joensen UN. Morbidity and Days Alive and Out of Hospital Within 90 Days Following Radical Cystectomy for Bladder Cancer. Eur Urol Open Sci. 2021 Apr 19;28:1-8. doi: 10.1016/j.euros.2021.03.010. eCollection 2021 Jun. PMID 34337519
• Andrijasevic N, Ovcaricek S, Butic I, Navratil M, Mili B. Comparison of the effectiveness of two combinations of antibiotic used for perioperative prophylactic therapy during radical cystectomy: A retrospective cohort study. Can Urol Assoc J. 2022 Nov;16(11):E539-E544. doi: 10.5489/cuaj.7859. PMID 35704932
• Lightner DJ, Wymer K, Sanchez J, Kavoussi L. Best Practice Statement on Urologic Procedures and Antimicrobial Prophylaxis. J Urol. 2020 Feb;203(2):351-356. doi: 10.1097/JU.0000000000000509. Epub 2019 Aug 23. PMID 31441676
• Villmones HC, Halland A, Stenstad T, Ulvestad E, Weedon-Fekjaer H, Kommedal O. The cultivable microbiota of the human distal ileum. Clin Microbiol Infect. 2021 Jun;27(6):912.e7-912.e13. doi: 10.1016/j.cmi.2020.08.021. Epub 2020 Aug 21. PMID 32835795
• Prunty M, Rhodes S, Rivero MJ, Callegari M, Jesse E, Arenas-Gallo C, Brant A, Calaway A, Scherr D, Shoag JE. National Adherence to Guidelines for Antimicrobial Prophylaxis for Patients Undergoing Radical Cystectomy. J Urol. 2023 Feb;209(2):329-336. doi: 10.1097/JU.0000000000003069. Epub 2022 Nov 16. PMID 36383758
• Mitropoulos D, Artibani W, Graefen M, Remzi M, Roupret M, Truss M; European Association of Urology Guidelines Panel. Reporting and grading of complications after urologic surgical procedures: an ad hoc EAU guidelines panel assessment and recommendations. Eur Urol. 2012 Feb;61(2):341-9. doi: 10.1016/j.eururo.2011.10.033. Epub 2011 Oct 29. PMID 22074761
• Maibom SL, Roder MA, Aasvang EK, Rohrsted M, Thind PO, Bagi P, Kistorp T, Poulsen AM, Salling LN, Kehlet H, Brasso K, Joensen UN. Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study. BJU Int. 2022 Jul;130(1):102-113. doi: 10.1111/bju.15619. Epub 2021 Nov 9. PMID 34657367
• Mitropoulos D, Artibani W, Biyani CS, Bjerggaard Jensen J, Roupret M, Truss M. Validation of the Clavien-Dindo Grading System in Urology by the European Association of Urology Guidelines Ad Hoc Panel. Eur Urol Focus. 2018 Jul;4(4):608-613. doi: 10.1016/j.euf.2017.02.014. Epub 2017 Mar 7. PMID 28753862

Идентификаторы

NCT: NCT06770530 · 2023-506226-36-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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