Duration of Perioperative Antibiotics in Pancreatoduodenectomy

Официальное название

Duration of Perioperative Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy: a Randomized Controlled Trial

Обзор

The goal of this clinical trial is to compare two perioperative antibiotic prophylaxis regimens in adult patients undergoing pancreatoduodenectomy (PD) or pylorus-preserving pancreatoduodenectomy (PPPD). The main question it aims to answer is: Is a single preoperative dose of cefazolin non-inferior to the conventional extended regimen (preoperative cefoxitin followed by 3 days of postoperative cefotaxime plus metronidazole) in preventing surgical site infection? Researchers will compare the single-dose cefazolin regimen with the conventional extended regimen to determine whether the shorter regimen results in a comparable rate of postoperative surgical site infection. Participants will be randomized 1:1 to one of the two regimens and followed for 30 days after surgery for surgical site infection and other infectious complications.

Подробное описание

1. Brief background Pancreatoduodenectomy (PD) is one of the major hepatobiliopancreatic surgical procedures, with postoperative infectious complication rates reaching approximately 20-40%. International guidelines recommend a single preoperative dose of cefazolin as antibiotic prophylaxis for PD. However, due to concerns about high infectious complication rates, some institutions administer antibiotics for more than 24 hours postoperatively. This study compares surgical site infection rates between the internationally recommended single-dose cefazolin regimen and the current practice at Asan Medical Center, which consists of a preoperative second-generation cephalosporin (cefoxitin) followed by postoperative cefotaxime plus metronidazole for 3 days. Through this comparison, the study seeks to contribute to establishing effective and safe antibiotic prophylaxis guidelines and to advancing antimicrobial stewardship efforts for this patient population. 2. Protocol summary

This phase III, single-center, randomized, non-inferiority trial conducted at Asan Medical Center, Seoul, compares two antibiotic prophylaxis regimens in adult patients undergoing PD or PPPD. A total of 558 participants will be enrolled over a two-year period from IRB approval, with follow-up through 30 days postoperatively. After informed consent and stratification by preoperative biliary stent status, participants will be randomized 1:1 to:

Single-dose arm: a single dose of cefazolin administered within 1 hour before skin incision.

Conventional (extended) arm: a single dose of cefoxitin within 1 hour before skin incision, followed by cefotaxime plus metronidazole on postoperative days 0-3.

The primary outcome is the incidence of surgical site infection within 30 days after surgery. 3. Statistical considerations The trial is designed to assess the non-inferiority of the single-dose cefazolin regimen relative to the conventional extended regimen. Assuming a 30-day surgical site infection rate of 20% in the control group, a non-inferiority margin of 10%, a one-sided alpha of 0.025, and 80% power, 252 participants per group (504 total) are required. Accounting for an anticipated 10% dropout rate, a total of 558 participants will be enrolled. The non-inferiority test for the difference between two independent proportions was used for sample size calculation (PASS software, version 15). 4. Analysis population The primary analysis will be performed on a modified intention-to-treat (mITT) basis, including all randomized participants who underwent pancreatic resection, regardless of the final resection type (e.g., conversion from planned pancreatoduodenectomy to total pancreatectomy). Participants who underwent surgical exploration without resection (open-and-close) are excluded, as they are not at risk for the primary endpoint. Participants are analyzed according to their randomized treatment assignment regardless of dosing protocol adherence. Sensitivity analyses, including a conservative intention-to-treat analysis and a per-protocol analysis, will also be performed.

Вмешательства

• Препарат single dose preoperative antibiotic
  Arm A is a single preoperative dose of cefazolin administered within 1 hour before surgery
• Препарат Prolonged perioperative antibiotics
  Preoperative Single-Dose Cefoxitin followed by Three-Day Cefotaxime and Metronidazole Prophylaxis

Первичные конечные точки

• Surgical site infection [Срок оценки: within 30 days after PD/PPPD]

Критерии участия

Критерии включения

• Male and female adults aged 18 to 80 years old scheduled for pancreaticoduodenectomy for any indication (including open, laparoscopic, and robotic surgery).
• Patients who have received sufficient explanation about this clinical trial and have voluntarily decided to participate and provided written informed consent.

Критерии исключения

• History of Type 1 immediate hypersensitivity reaction to cefazolin, cefotaxime, or metronidazole.
• Active or uncontrolled infection prior to surgery for which treatment has not been completed.
• Use of antibiotics for any reason within 1 week prior to surgery.
• Long-term use of immunosuppressants due to other concomitant diseases.
• Undergoing dialysis or having renal dysfunction of KDIGO Grade 3 or higher (GFR < 45).
• Pregnancy or breastfeeding.

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

Открытое

Основная цель

Профилактика

Центры проведения

South Korea · 1 центр

• Asan Medical Center — Seoul

Публикации

• Hwang DW, Kim HJ, Lee JH, Song KB, Kim MH, Lee SK, Choi KT, Jun IG, Bang JY, Kim SC. Effect of Enhanced Recovery After Surgery program on pancreaticoduodenectomy: a randomized controlled trial. J Hepatobiliary Pancreat Sci. 2019 Aug;26(8):360-369. doi: 10.1002/jhbp.641. Epub 2019 Jul 2. PMID 31152686
• Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American Society of Health-System Pharmacists (ASHP); Infectious Diseases Society of America (IDSA); Surgical Infection Society (SIS); Society for Healthcare Epidemiology of America (SHEA). Clinical practice guidelines for antimicrobial prophylaxis in surger PMID 23461695
• Boyev A, Arvide EM, Newhook TE, Prakash LR, Bruno ML, Dewhurst WL, Kim MP, Maxwell JE, Ikoma N, Snyder RA, Lee JE, Katz MHG, Tzeng CD. Prophylactic Antibiotic Duration and Infectious Complications in Pancreatoduodenectomy Patients With Biliary Stents: Opportunity for De-escalation. Ann Surg. 2024 Apr 1;279(4):657-664. doi: 10.1097/SLA.0000000000005982. Epub 2023 Jul 3. PMID 37389897
• D'Angelica MI, Ellis RJ, Liu JB, Brajcich BC, Gonen M, Thompson VM, Cohen ME, Seo SK, Zabor EC, Babicky ML, Bentrem DJ, Behrman SW, Bertens KA, Celinski SA, Chan CHF, Dillhoff M, Dixon MEB, Fernandez-Del Castillo C, Gholami S, House MG, Karanicolas PJ, Lavu H, Maithel SK, McAuliffe JC, Ott MJ, Reames BN, Sanford DE, Sarpel U, Scaife CL, Serrano PE, Smith T, Snyder RA, Talamonti MS, Weber SM, Yopp PMID 37078771
• Sugawara G, Yokoyama Y, Ebata T, Mizuno T, Yagi T, Ando M, Nagino M. Duration of Antimicrobial Prophylaxis in Patients Undergoing Major Hepatectomy With Extrahepatic Bile Duct Resection: A Randomized Controlled Trial. Ann Surg. 2018 Jan;267(1):142-148. doi: 10.1097/SLA.0000000000002049. PMID 27759623
• Yamamoto T, Satoi S, Fujii T, Yamada S, Yanagimoto H, Yamaki S, Takami H, Hirooka S, Kosaka H, Kotsuka M, Miyara T, Kodera Y. Dual-center randomized clinical trial exploring the optimal duration of antimicrobial prophylaxis in patients undergoing pancreaticoduodenectomy following biliary drainage. Ann Gastroenterol Surg. 2018 Sep 17;2(6):442-450. doi: 10.1002/ags3.12209. eCollection 2018 Nov. PMID 30460348
• Okamura K, Tanaka K, Miura T, Nakanishi Y, Noji T, Nakamura T, Tsuchikawa T, Okamura K, Shichinohe T, Hirano S. Randomized controlled trial of perioperative antimicrobial therapy based on the results of preoperative bile cultures in patients undergoing biliary reconstruction. J Hepatobiliary Pancreat Sci. 2017 Jul;24(7):382-393. doi: 10.1002/jhbp.453. Epub 2017 May 6. PMID 28371248

Идентификаторы

NCT: NCT07043855 · 2025-0529

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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