15 vs 45 Minute Pringle Maneuver in Liver Cancer Resection: Randomized Noninferiority Trial

Официальное название

A Prospective, Randomized Noninferiority Trial Comparing 15- and 45-minute Pringle Maneuvers During Liver Resection for Oncologic Indications.

Обзор

The goal of this clinical trial is to evaluate the safety of two durations of the Pringle maneuver in adults undergoing elective liver resection for malignant tumors. The main questions it aims to answer are: Is the incidence of post-hepatectomy liver failure different between 15-minute and 45-minute Pringle maneuver durations? * Do the durations differ in operative time or intraoperative blood loss? * Researchers will compare patients randomized 1:1 to 15 minutes vs 45 minutes of Pringle clamping to see if outcomes are non-inferior between groups. Participants will: * Undergo standard oncologic hepatectomy with the assigned Pringle duration. * Receive routine perioperative assessments, including laboratory tests and clinical evaluations. * Attend follow-up visits at approximately 6 months, 1 year, and 3 years after surgery.

Подробное описание

Participants who meet the inclusion criteria and provide written informed consent will be randomly assigned, using block randomization with a block size of 10, to one of two study groups. In Group 1, Pringle maneuvers lasting 15 minutes with a 10-minute reperfusion interval will be applied during liver resection. In Group 2, Pringle maneuvers lasting 45 minutes with a 15-minute reperfusion interval will be used. In both groups, the Pringle maneuver will be repeated as needed until completion of liver parenchymal transection. If transection is completed earlier, the maneuver will be discontinued before the randomized time. The operating surgeon and anesthesiologist may also decide to start or interrupt the Pringle maneuver outside the predefined time frames if intraoperative conditions require it.

During each Pringle maneuver, the patient's status will be monitored according to standard practice for liver resection, including blood pressure measurement, urine output, and arterial blood gas analysis. The number and duration of Pringle maneuvers, arterial blood pressure values, the type and doses of vasopressors used, serum lactate levels, the duration of parenchymal transection, total operative time, intraoperative blood loss, and hourly urine output will be recorded in perioperative case report forms.

In the postoperative period, laboratory tests will be performed on postoperative days 0, 1, 3, and 5. The occurrence of postoperative complications up to the time of hospital discharge will be documented in the patient's electronic medical record. Outcomes will be assessed by in-person outpatient visits or telemedicine consultations at approximately 6 months, 1 year, and 3 years after surgery.

The sample size was calculated using the Wald method. Based on an analysis of archival data from the Department of Transplantation and Liver Surgery, the incidence of post-hepatectomy liver failure according to the ISGLS definition is approximately 4%. Assuming 80% power, a one-sided significance level of 0.05, and a noninferiority margin of 5%, 300 participants will be enrolled in each arm.

Collected study data will be analyzed with particular attention to the duration of the Pringle maneuver, the extent and technical complexity of the resection, the primary diagnosis, and the presence of coexisting liver disease, in order to determine their influence on the study endpoints.

An interim analysis is planned after recruitment of 50% of the target sample size. If the interim analysis demonstrates a negative effect of the intervention on postoperative complications, further enrollment will be discontinued.

Вмешательства

• Процедура Pringle manouver
  The Pringle maneuver involves temporary clamping of the hepatic pedicle during liver resection to reduce blood loss during parenchymal transection.

Первичные конечные точки

• Posthepatectomy liver failure [Срок оценки: On or after postoperative day 5]

Вторичные конечные точки (2)

• Intraoperative blood loss [Срок оценки: At the completion of the surgery]
• Parenchymal transection time [Срок оценки: At the completion of the surgery]

Критерии участия

Критерии включения

• Diagnosis of a primary or secondary malignant liver tumor.
• Age > 18 years.
• Patient deemed eligible for liver resection.
• WHO performance status ≤ 2.
• Ability to provide written informed consent.

Критерии исключения

• Liver cirrhosis.
• Liver dysfunction classified as Child-Pugh class B or C.
• Repeat hepatectomy.
• Prior ablation or chemoembolization of hepatic lesions.
• Prior portal vein branch embolization.
• Planned or performed ALPPS procedure.
• Concomitant resection of any organ other than the gallbladder during the same operation.

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

Другое

Центры проведения

Польша · 1 центр

• Department of General, Transplant and Liver Surgery, Medical University of Warsaw — Warsaw

Публикации

• Wang HP, Hou TY, Li WF, Yong CC. Inflow control can be safely used in laparoscopic subsegmentectomy of the liver: a single-center 10-year experience. BMC Surg. 2023 Dec 6;23(1):366. doi: 10.1186/s12893-023-02282-2. PMID 38057769
• van den Broek MA, Bloemen JG, Dello SA, van de Poll MC, Olde Damink SW, Dejong CH. Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery. J Hepatol. 2011 Aug;55(2):337-45. doi: 10.1016/j.jhep.2010.11.024. Epub 2010 Dec 13. PMID 21147188
• Doi S, Yasuda S, Hokuto D, Kamitani N, Matsuo Y, Sakata T, Nishiwada S, Nagai M, Nakamura K, Terai T, Kohara Y, Sho M. Impact of the Prolonged Intermittent Pringle Maneuver on Post-Hepatectomy Liver Failure: Comparison of Open and Laparoscopic Approaches. World J Surg. 2023 Dec;47(12):3328-3337. doi: 10.1007/s00268-023-07201-3. Epub 2023 Oct 3. PMID 37787778
• Liu J, Wang W, Shi C, Li C, Xue F, Hu L, Wang Y, Ge R. The difference in prolonged continuous and intermittent Pringle maneuver during complex hepatectomy for hepatocellular carcinoma patients with chronic liver disease: A retrospective cohort study. Cancer Med. 2021 Dec;10(23):8507-8517. doi: 10.1002/cam4.4361. Epub 2021 Oct 18. PMID 34658153
• Fagenson AM, Gleeson EM, Nabi F, Lau KN, Pitt HA. When does a Pringle Maneuver cause harm? HPB (Oxford). 2021 Apr;23(4):587-594. doi: 10.1016/j.hpb.2020.07.014. Epub 2020 Sep 12. PMID 32933844
• Huang Y, Liao A, Pu X, Yang J, Lv T, Yan L, Yang J, Wu H, Jiang L. A randomized controlled trial of effect of 15- or 25-minute intermittent Pringle maneuver on hepatectomy for hepatocellular carcinoma. Surgery. 2022 Jun;171(6):1596-1604. doi: 10.1016/j.surg.2021.11.012. Epub 2021 Dec 13. PMID 34916072

Идентификаторы

NCT: NCT07237204 · KB/115/2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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