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

  • STATUS
    Recruiting
  • End date
    Oct 15, 2022
  • participants needed
    60
  • sponsor
    Nanfang Hospital of Southern Medical University
Updated on 22 August 2021

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.

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.

Details
Condition Acute Variceal Bleeding, Renal Function Disorder
Treatment Octreotide, Terlipressin
Clinical Study IdentifierNCT04028323
SponsorNanfang Hospital of Southern Medical University
Last Modified on22 August 2021

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note