The Effect of Terlipressin on Recovery of Liver Function After Hepatectomy

Study on the Effect of Terlipressin on Recovery of Liver Function After Hepatectomy: a Multicenter Randomized Controlled Study

Portal vein hypertension is associated with post-hepatectomy liver failure in patients with liver cirrhosis. Our previous study found that bolus injection of 1 mg terlipressin immediately after hepatectomy decreased portal vein pressure, and post-operative continuous use of terlipressin decreased the amount of abdominal drain. In this multicenter randomized controlled study, we aim to evaluate the effects of terlipressin in the patients who underwent liver resection complicated by portal vein hypertension.

Study Overview

• Status: Unknown
• Conditions: Liver Failure; Acute Kidney Injury; Ascites Hepatic; Terlipressin Adverse Reaction
• Intervention / Treatment: Drug: Terlipressin plus standard care; Other: Standard care

Detailed Description

Portal vein hypertension is associated with post-hepatectomy liver failure in patients with liver cirrhosis. Our previous study found that bolus injection of 1 mg terlipressin immediately after hepatectomy decreased portal vein pressure, and post-operative continuous use of terlipressin decreased the amount of abdominal drain. In this multicenter randomized controlled study, we aim to evaluate the effects of terlipressin in the patients who underwent liver resection complicated by portal vein hypertension. The primary outcome is the total abdominal drain on postoperative day (POD) 1 to 3. The secondary outcomes are: (1) the incidence of post-hepatectomy liver failure; (2) post-operative acute kidney injury; (3) the side effects of terlipressin.

• Study Type: Interventional
• Enrollment (Anticipated): 86
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiao-Dong Zhu, MD&PhD; Phone Number: +862164041990; Email: zhuxiaodong@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital affiliated to Shanghai Jiaotong University
      • Contact: Yongjun Chen
    • Shanghai, Shanghai, China, 200092
      • Recruiting
      • Xinhua Hospital Affiliated To Shanghai Jiao Tong University
      • Contact: Jiandong Wang
    • Shanghai, Shanghai, China, 200438
      • Recruiting
      • Eastern Hepatobiliary Surgery Hospital, Second Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects signed informed consent.
• An open liver resection is planned.
• Hepatitis B virus infection background.
• Pre-operative liver function is Child-Pugh A.
• Subjects with clinical significance portal vein hypertension or the liver stiffness > 12 kPa before surgery.
• Portal vein pressure > 12 mmHg at 5 min after liver resection.

Exclusion Criteria:

• Age < 18 y or > 75 y.
• Subjects received anti-cancer therapy within 3 months before surgery, or with a history of open or laparoscopic surgery.
• Portal vein tumor thrombus was confirmed by preoperative imaging study.
• Obstruction of biliary tract.
• Pre-operative ALT or AST > 2×ULN.
• A history of myocardial infarction or chronic kidney disease.
• Severe arrhythmia.
• Intraoperative portal vein pressure could not be measured technically.
• Any other contraindications of the terlipressin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Terlipressin plus standard care; Immediately after hepatectomy, 1 mg terlipressin was given intravenously after hemostasis was achieved. After surgery, participants were routinely managed, and terlipressin were administrated at a dosage of 2 mg per day for 4 days.	Drug: Terlipressin plus standard care; All the participants received routine care after surgery. Intraoperative 1 mg, and 1 mg q12h from post-operative day 1 through day 4.; Other Names: terlipressin infusion plus routine care
OTHER: Standard care; Participants were not administrated with terlipressin during surgery and were routinely managed after surgery.	Other: Standard care; All the participants received routine care after surgery only.; Other Names: routine care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total abdominal drainage	from postoperative day 1 through day 3.	From post-operative day 1 to day 4.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of post-hepatectomy liver failure	based on the criteria of ISGLS 2011.	From post-operative day 1 to day 30.
The incidence of acute kidney injury	defined as an absolute increase in serum creatinine (Cr) ≥ 0.3 mg/dl (26.5 μmol/L) and/or ≥ 50% from baseline	From post-operative day 1 to day 30.
The side effects of terlipressin	the incidences of abdominal pain, diarrhea, headache, hyponatremia, and hypertension	From post-operative day 1 to day 30.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Publications and helpful links

General Publications

• Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, Bernardi M, Romanelli RG, Colletta C, Salinas F, Di Giacomo A, Ridola L, Fornasiere E, Caraceni P, Morando F, Piano S, Gatta A, Angeli P; Italian Association for the Study of the Liver Study Group on Hepatorenal Syndrome. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015 Aug;62(2):567-74. doi: 10.1002/hep.27709. Epub 2015 Feb 13.
• Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011 May;149(5):713-24. doi: 10.1016/j.surg.2010.10.001. Epub 2011 Jan 14.
• Chen X, Zhai J, Cai X, Zhang Y, Wei L, Shi L, Wu D, Shen F, Lau WY, Wu M. Severity of portal hypertension and prediction of postoperative liver failure after liver resection in patients with Child-Pugh grade A cirrhosis. Br J Surg. 2012 Dec;99(12):1701-10. doi: 10.1002/bjs.8951.
• Saner FH, Canbay A, Gerken G, Broelsch CE. Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007 Dec;1(2):207-17. doi: 10.1586/17474124.1.2.207.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 7, 2019
• Primary Completion (ANTICIPATED): December 30, 2020
• Study Completion (ANTICIPATED): December 30, 2020

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (ACTUAL): January 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: acute kidney injury; liver failure; terlipressin; hepatectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Liver Failure; Hepatic Insufficiency; Ascites; Acute Kidney Injury; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: Terlipressin-Hepatectomy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No