Functional MRI-based Assessment of Terlipressin vs. Octreotide on Renal Function in Cirrhotic Patients With Acute Variceal Bleeding (CHESS1903)

NCT04028323 | Unknown Phase 4 DMC

• 1 other identifier: CHESS1903
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

Acute variceal bleeding is one of the critical complications in patients with cirrhosis. Due to remarkable improvements in diagnostic and therapeutic modalities such as vasoactive agents, endoscopic therapy and antibiotics, the overall prognosis has been improved during the past several decades. However, it is still associated with increased mortality that is still around 20% at 6 weeks. Patients with advanced cirrhosis have an intense overactivity of the endogenous vasoactive systems characterized by arterial hypotension and low peripheral vascular resistance. Severe renal vasoconstriction in consequence of marked arterial vasodilatation in splanchnic circulation triggers the reduction of glomerular filtration rate, and thus induces acute kidney injury (AKI)/hepatorenal syndrome (HRS), which have been further implicated in the increasing mortality in patients with cirrhosis. Renal functional magnetic resonance imaging (fMRI), a technique considered superior to the most common method used to estimate the glomerular filtration rate, allows for non-invasive, accurate measurements of renal structures and functions in both animals and humans. It has become increasingly prevalent in research and clinical applications. In recent years, renal fMRI has developed rapidly with progress in MRI hardware and emerging post-processing algorithms. Function related imaging markers could be acquired via renal fMRI, encompassing water molecular diffusion, perfusion, and oxygenation. The study will use phase contrast - MR angiography, intravoxel incoherent motion - diffusion weighted imaging (IVIM-DWI) and blood-oxgen-level-dependent (BOLD)-MRI to evaluate renal functional changes after using vasoactive medications in patients with cirrhosis. The rationale for the use of vasoactive medications, including terlipressin and octreotide, is to produce splanchnic vasoconstriction and reduce portal blood flow and portal pressure, thereby underpinning the application of these vasoactive drugs in the management of cirrhotic patients with acute variceal bleeding. Meanwhile, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS because terlipressin may improve renal hemodynamics, improve renal function and potentially enable HRS a reversible condition without the need of liver transplantation. However, the renal protection effect of terlipressin vs. octreotide remains unknown. In this study, the investigators aim to conduct a multicenter, single-blind randomized controlled trial to compare the renal protection effect of terlipressin vs. octreotide assessed by fMRI in the management of cirrhotic patients with acute variceal bleeding.

Conditions

Renal Function Disorder; Acute Variceal Bleeding

Keywords

Functional MRI; Terlipressin; Octreotide; Renal function disorder; Acute variceal bleeding

Outcome Measures

Primary Outcomes (1)

• Renal function

  Number of participants with the improvement of renal function assessed by serum creatinine

  6 days

Secondary Outcomes (7)

• Renal perfusion

  6 days

• Renal blood oxygenation

  6 days

• Failure to control bleeding

  6 days

• Intra-hospital rebleeding

  6 days

• Intra-hospital mortality

  6 days

Study Arms (2)

Experimental group

EXPERIMENTAL

Drug: Terlipressin. Terlipressin should be administrated with an initial dose of 1-2 mg intravenously and slowly injected (over 1 minute) while monitoring the heart rate and blood pressure. The maintenance dose should be administrated every 4-6 hours. Each dose of terlipressin is 1mg. The usual duration of therapy is 3-5 days.

Drug: Terlipressin

Control group

ACTIVE COMPARATOR

Drug: Octreotide. Octreotide should be continuously and intravenously dripped at the speed of 0.025-0.05 mg/h and could be diluted with saline with the maximum duration of 5 days. The usual duration of therapy is 3-5 days.

Drug: Octreotide

Interventions

Terlipressin DRUG

Terlipressin should be administrated intravenously while monitoring heart rate and blood pressure daily.

Experimental group

Octreotide DRUG

Octreotide should be continuously intravenously administrated while monitoring heart rate and blood pressure daily.

Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinically and/or pathologically diagnosed cirrhosis
• with a clinical history of acute variceal bleeding (melena, hematemesis etc.) assessed as Child-Pugh class B or C
• voluntarily participated in the study and able to provide written informed consent and able to understand and willing to comply with the requirements of the study

You may not qualify if:

• pregnant or lactating woman
• diagnosed or suspected malignancy (hepatocellular carcinoma, cholangiocarcinoma etc.)
• with mental disease and unable to comply with MRI examination
• with contraindications of terlipressin and octreotide
• with other conditions judged inadequate for participation by the investigators.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• LanZhou University: collaborator
• Zhongda Hospital: collaborator
• Guangdong Second Provincial General Hospital: collaborator
• Xingtai People's Hospital: collaborator
• The Third Hospital of Zhenjiang Affiliated Jiangsu University: collaborator
• Tianjin Second People's Hospital: collaborator
• The Second Hospital of Anhui Medical University: collaborator
• The Sixth People's Hospital of Shenyang: collaborator
• The Second Affiliated Hospital of Baotou Medical College: collaborator

Study Sites (10)

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

NOT YET RECRUITING

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

RECRUITING

Guangdong Second Provincial General Hospital

Guangzhou, Guangdong, China

NOT YET RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

Xingtai People's Hospital

Xingtai, Hebei, China

NOT YET RECRUITING

Zhongda Hospital, Medical School, Southeast University

Nanjing, Jiangsu, China

NOT YET RECRUITING

The Third Hospital of Zhenjiang Affiliated Jiangsu University

Zhenjiang, Jiangsu, China

NOT YET RECRUITING

The Sixth People's Hospital of Shenyang

Shenyang, Liaoning, China

NOT YET RECRUITING

The Second Affiliated Hospital of Baotou Medical University

Baotou, Neimenggu, China

NOT YET RECRUITING

Tianjin Second People's Hospital

Tianjin, Tianjin Municipality, China

NOT YET RECRUITING

Related Publications (11)

• Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009 Sep 24;361(13):1279-90. doi: 10.1056/NEJMra0809139. No abstract available.

  PMID: 19776409 BACKGROUND

• Ibrahim M, Mostafa I, Deviere J. New Developments in Managing Variceal Bleeding. Gastroenterology. 2018 May;154(7):1964-1969. doi: 10.1053/j.gastro.2018.02.023. Epub 2018 Mar 2.

  PMID: 29481777 BACKGROUND

• Wong F. Recent advances in our understanding of hepatorenal syndrome. Nat Rev Gastroenterol Hepatol. 2012 May 22;9(7):382-91. doi: 10.1038/nrgastro.2012.96.

  PMID: 22614754 BACKGROUND

• Martin-Llahi M, Pepin MN, Guevara M, Diaz F, Torre A, Monescillo A, Soriano G, Terra C, Fabrega E, Arroyo V, Rodes J, Gines P; TAHRS Investigators. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008 May;134(5):1352-9. doi: 10.1053/j.gastro.2008.02.024. Epub 2008 Feb 14.

  PMID: 18471512 BACKGROUND

• Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat JL. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet. 1995 Sep 30;346(8979):865-8. doi: 10.1016/s0140-6736(95)92708-5.

  PMID: 7564670 BACKGROUND

• Seo YS, Park SY, Kim MY, Kim JH, Park JY, Yim HJ, Jang BK, Kim HS, Hahn T, Kim BI, Heo J, An H, Tak WY, Baik SK, Han KH, Hwang JS, Park SH, Cho M, Um SH. Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage. Hepatology. 2014 Sep;60(3):954-63. doi: 10.1002/hep.27006. Epub 2014 Jul 25.

  PMID: 24415445 BACKGROUND

• Abid S, Jafri W, Hamid S, Salih M, Azam Z, Mumtaz K, Shah HA, Abbas Z. Terlipressin vs. octreotide in bleeding esophageal varices as an adjuvant therapy with endoscopic band ligation: a randomized double-blind placebo-controlled trial. Am J Gastroenterol. 2009 Mar;104(3):617-23. doi: 10.1038/ajg.2008.147. Epub 2009 Feb 17.

  PMID: 19223890 BACKGROUND

• 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.

  PMID: 25644760 BACKGROUND

• Wang YC, Tang A, Chang D, Zhang SJ, Ju S. Significant perturbation in renal functional magnetic resonance imaging parameters and contrast retention for iodixanol compared with iopromide: an experimental study using blood-oxygen-level-dependent/diffusion-weighted magnetic resonance imaging and computed tomography in rats. Invest Radiol. 2014 Nov;49(11):699-706. doi: 10.1097/RLI.0000000000000073.

  PMID: 24879299 BACKGROUND

• Chang D, Wang YC, Xu TT, Peng XG, Cai Y, Wang L, Bai YY, Ju S. Noninvasive Identification of Renal Hypoxia in Experimental Myocardial Infarctions of Different Sizes by Using BOLD MR Imaging in a Mouse Model. Radiology. 2018 Jan;286(1):129-139. doi: 10.1148/radiol.2017161998. Epub 2017 Aug 4.

  PMID: 28777704 BACKGROUND

• Yan X, Shao R, Wang Y, Mao X, Lei J, Zhang L, Zheng J, Liu A, Zhao H, Gao F, Wang J, Li P, Yao S, Xu M, Xu J, Liu D, Mi Y, Gong X, Ye J, Deng M, Dang T, Ji J, Shao C, Liu C, Gu Y, Wu Y, Wang F, Teng G, Li X, Qi X, Ju S, Qi X. Functional magnetic resonance imaging-based assessment of terlipressin vs. octreotide on renal function in cirrhotic patients with acute variceal bleeding (CHESS1903): study protocol of a multicenter randomized controlled trial. Ann Transl Med. 2019 Oct;7(20):586. doi: 10.21037/atm.2019.09.141.

  PMID: 31807567 DERIVED

MeSH Terms

Interventions

Terlipressin; Octreotide

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Shenghong Ju, MD

  Zhongda Hospital

  PRINCIPAL INVESTIGATOR

• Xingshun Qi, MD

  General Hospital of Shenyang Military Area

  PRINCIPAL INVESTIGATOR

• Xiaolong Qi, MD

  LanZhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaolong Qi, MD

CONTACT

86-18588602600; qixiaolong@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Hepatic Hemodynamic Lab

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 22, 2019
• Study Start: July 16, 2019
• Primary Completion: July 15, 2020
• Study Completion: October 15, 2022
• Last Updated: August 17, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)