Functional MRI-based Assessment of Terlipressin vs. Octreotide on Renal Function in Cirrhotic Patients With Acute Variceal Bleeding (CHESS1903)
- Conditions
- Renal Function DisorderAcute Variceal Bleeding
- Interventions
- Registration Number
- NCT04028323
- Lead Sponsor
- Nanfang Hospital, 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental group Terlipressin 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. Control group Octreotide 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.
- Primary Outcome Measures
Name Time Method Renal function 6 days Number of participants with the improvement of renal function assessed by serum creatinine
- Secondary Outcome Measures
Name Time Method Failure to control bleeding 6 days The occurrence rate of failure to control bleeding
Renal perfusion 6 days Number of participants with the improvement of renal perfusion assessed by functional MRI measurement (intravoxel incoherent motion)
Renal blood oxygenation 6 days Number of participants with the improvement of renal blood oxygenation assessed by functional MRI measurement (blood oxygen level dependent)
Intra-hospital mortality 6 days The occurrence rate of intra-hospital mortality
Intra-hospital rebleeding 6 days The occurrence rate of intra-hospital rebleeding
Adverse events 6 days The occurrence rate of adverse events
Overall survival 90 days The number of participants still alive with the 90 days follow-up
Trial Locations
- Locations (10)
The First Hospital of Lanzhou University
π¨π³Lanzhou, Gansu, China
The Second Affiliated Hospital of Anhui Medical University
π¨π³Hefei, Anhui, China
Guangdong Second Provincial General Hospital
π¨π³Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
π¨π³Guangzhou, Guangdong, China
Zhongda Hospital, Medical School, Southeast University
π¨π³Nanjing, Jiangsu, China
The Third Hospital of Zhenjiang Affiliated Jiangsu University
π¨π³Zhenjiang, Jiangsu, China
The Second Affiliated Hospital of Baotou Medical University
π¨π³Baotou, Neimenggu, China
The Sixth People's Hospital of Shenyang
π¨π³Shenyang, Liaoning, China
Tianjin Second People's Hospital
π¨π³Tianjin, Tianjin, China
Xingtai People's Hospital
π¨π³Xingtai, Hebei, China