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

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ClinicalTrials.gov Identifier: NCT04028323
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : July 22, 2019
Sponsor:
Collaborators:
LanZhou University
Zhongda Hospital, Medical School, Southeast University
Guangdong Second Provincial General Hospital
Xingtai People's Hospital
The Third Hospital of Zhenjiang Affiliated Jiangsu University
Tianjin Second People's Hospital
the Second Affiliated Hospital of Anhui Medical University
The Sixth People Hospital of Shenyang
The Second Affiliated Hospital of Baotou Medical University
Information provided by (Responsible Party):
Xiaolong Qi, Nanfang Hospital of Southern Medical University

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.


Condition or disease Intervention/treatment Phase
Renal Function Disorder Acute Variceal Bleeding Drug: Terlipressin Drug: Octreotide Phase 4

Detailed Description:

Gastroesophageal varices, the most relevant portal-system collaterals, and acute variceal bleeding are critical complications that result directly from portal hypertension in patients with cirrhosis. Gastroesophageal varices are present approximately in 50% of patients with cirrhosis. Their presence correlates with the severity of liver disease. Only 40% of Child-Pugh A patients have varices whilst 85% of the occurrence rate in Child-Pugh C patients. 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, which is still around 20% at 6 weeks. Acute variceal bleeding is also responsible for a variety of other complications in patients with cirrhosis including acute on chronic liver failure, hepatorenal syndrome, ascites liquid infection and hepatic encephalopathy. Therefore, timely and effective control of acute variceal bleeding is of crucial importance for the prognosis in patients with cirrhosis.

In the early stages of cirrhosis, when portal hypertension is moderate, increased cardiac output compensated for a modest reduction in the systemic vascular resistance, ensuring the arterial pressure and effective arterial blood volume to maintain within the normal limits. Patients with advanced cirrhosis have an intense overactivity of the endogenous vasoactive systems characterized by arterial hypotension and low peripheral vascular resistance. This cascade of events sets the stage for further renal vasoconstriction and renal sodium retention as the splanchnic and systemic vasodilatation worsens with the progression of cirrhosis. 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)/ hepato-renal syndrome (HRS) which may implicate 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 in patients 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: Functional MRI-based Assessment of Terlipressin vs. Octreotide on Renal Function in Cirrhotic Patients With Acute Variceal Bleeding (CHESS1903): A Multicenter, Single-blind, Randomised Controlled Trial
Actual Study Start Date : July 16, 2019
Estimated Primary Completion Date : July 15, 2020
Estimated Study Completion Date : October 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental group
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
Terlipressin should be administrated intravenously while monitoring heart rate and blood pressure daily.

Active Comparator: Control group
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
Octreotide should be continuously intravenously administrated while monitoring heart rate and blood pressure daily.




Primary Outcome Measures :
  1. Renal function [ Time Frame: 6 days ]
    Number of participants with the improvement of renal function assessed by serum creatinine


Secondary Outcome Measures :
  1. Renal perfusion [ Time Frame: 6 days ]
    Number of participants with the improvement of renal perfusion assessed by functional MRI measurement (intravoxel incoherent motion)

  2. Renal blood oxygenation [ Time Frame: 6 days ]
    Number of participants with the improvement of renal blood oxygenation assessed by functional MRI measurement (blood oxygen level dependent)

  3. Failure to control bleeding [ Time Frame: 6 days ]
    The occurrence rate of failure to control bleeding

  4. Intra-hospital rebleeding [ Time Frame: 6 days ]
    The occurrence rate of intra-hospital rebleeding

  5. Intra-hospital mortality [ Time Frame: 6 days ]
    The occurrence rate of intra-hospital mortality

  6. Adverse events [ Time Frame: 6 days ]
    The occurrence rate of adverse events

  7. Overall survival [ Time Frame: 90 days ]
    The number of participants still alive with the 90 days follow-up



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028323


Contacts
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Contact: Xiaolong Qi, MD 86-18588602600 qixiaolong@vip.163.com

Locations
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China, Anhui
The Second Affiliated Hospital of Anhui Medical University Not yet recruiting
Hefei, Anhui, China
Contact: Xiangpeng Hu, MD         
Principal Investigator: Xiangpeng Hu, MD         
China, Gansu
The First Hospital of Lanzhou University Recruiting
Lanzhou, Gansu, China
Contact: Xiaorong Mao, MD         
Principal Investigator: Xiaorong Mao, MD         
China, Guangdong
Guangdong Second Provincial General Hospital Not yet recruiting
Guangzhou, Guangdong, China
Contact: Ming Xu, MD         
Principal Investigator: Ming Xu, MD         
Nanfang Hospital of Southern Medical University Not yet recruiting
Guangzhou, Guangdong, China
Contact: Jinjun Chen, MD         
Principal Investigator: Jinjun Chen, MD         
China, Hebei
Xingtai People's Hospital Not yet recruiting
Xingtai, Hebei, China
Contact: Dengxiang Liu, MD         
Principal Investigator: Dengxiang Liu, MD         
China, Jiangsu
Zhongda Hospital, Medical School, Southeast University Not yet recruiting
Nanjing, Jiangsu, China
Contact: Ruihua Shi, MD         
Principal Investigator: Ruihua Shi, MD         
The Third Hospital of Zhenjiang Affiliated Jiangsu University Not yet recruiting
Zhenjiang, Jiangsu, China
Contact: Shengqiang Zou, MD         
Principal Investigator: Shengqiang Zou, MD         
China, Liaoning
The Sixth People's Hospital of Shenyang Not yet recruiting
Shenyang, Liaoning, China
Contact: Yi Ma, MD         
Principal Investigator: Yi Ma, MD         
China, Neimenggu
The Second Affiliated Hospital of Baotou Medical University Not yet recruiting
Baotou, Neimenggu, China
Contact: Limei Ren, MD         
Principal Investigator: Limei Ren, MD         
China, Tianjin
Tianjin Second People's Hospital Not yet recruiting
Tianjin, Tianjin, China
Contact: Jia Li, MD         
Principal Investigator: Jia Li, MD         
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
LanZhou University
Zhongda Hospital, Medical School, Southeast University
Guangdong Second Provincial General Hospital
Xingtai People's Hospital
The Third Hospital of Zhenjiang Affiliated Jiangsu University
Tianjin Second People's Hospital
the Second Affiliated Hospital of Anhui Medical University
The Sixth People Hospital of Shenyang
The Second Affiliated Hospital of Baotou Medical University
Investigators
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Principal Investigator: Shenghong Ju, MD Zhongda Hospital, Medical School, Southeast University
Principal Investigator: Xingshun Qi, MD General Hospital of Shenyang Military Area
Principal Investigator: Xiaolong Qi, MD LanZhou University

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Xiaolong Qi, Principal Investigator, Hepatic Hemodynamic Lab, Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT04028323    
Other Study ID Numbers: CHESS1903
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xiaolong Qi, Nanfang Hospital of Southern Medical University:
Functional MRI
Terlipressin
Octreotide
Renal function disorder
Acute variceal bleeding
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemorrhage
Pathologic Processes
Octreotide
Terlipressin
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antihypertensive Agents
Vasoconstrictor Agents