A New Screening Strategy for Varices (LSSM-RCT)

January 23, 2018 updated by: Prof Wong, Lai Hung Grace, Chinese University of Hong Kong

A Randomized Controlled Trial of a New Screening Strategy for Varices Based on Liver and Spleen Stiffness Measurement (LSSM) in Cirrhotic Patients

Liver cirrhosis is an advanced stage of chronic liver diseases, which is often associated with various complications, namely esophageal and/or gastric varices, ascites, hepatocellular carcinoma (HCC). It is well known that the risk of complications varies even among cirrhotic patients, as those with more advanced disease would have more complications and poorer survival rates. Liver stiffness measurement (LSM) with transient elastography is found useful to identify cirrhotic patients with higher risk of portal hypertension and presence of varices . Recently, spleen stiffness measurement (SSM) with the same machine was found accurate to predict portal hypertension and esophageal varices.

Investigators hypothesized that a new screening strategy guided by LSM and SSM (LSSM) values (LSSM-guided) is non-inferior to conventional strategy in terms of detection rate of clinically significant esophageal and/or gastric varices for patients with liver cirrhosis in an open-labeled randomized controlled trial.

Consecutive patients with compensated liver cirrhosis will be invited for the study. Patients fulfilling the study criteria will be randomized into LSSM arm (upper endoscopy only performed to patients with high LSM or SSM values), and control arm (upper endoscopy performed to all patients). Patients randomized into LSSM arm will undergo transient elastography examination; those with high LSM or SSM results will be referred for upper endoscopy examination for to screen varices. Patients randomized into control arm will be directly referred for upper endoscopy examination.

Study Overview

Status

Completed

Conditions

Detailed Description

Liver cirrhosis is an advanced stage of chronic liver diseases, which is often associated with various complications, namely esophageal and/or gastric varices, ascites, hepatocellular carcinoma (HCC). It is well known that the risk of complications varies even among cirrhotic patients, as those with more advanced disease would have more complications and poorer survival rates. Liver stiffness measurement (LSM) with transient elastography is found useful to identify cirrhotic patients with higher risk of portal hypertension and presence of varices at cross-sectional basis. LSM cutoff values of 17.6 kPa and 21.0 kPa would have the sensitivity ≥ 90% in order to detect patients with hepatic venous pressure gradient (HVPG) above 10-12mmHg , while the presence of varices could be confidently excluded with a liver stiffness below 12.5-19.8 kPa. However, these suggested cutoff values overlap with those for detecting histologic cirrhosis in most chronic liver diseases. Hence there seems no significant additional information provided by LSM regarding screening endoscopy for varices among cirrhotic patients.

Recently, spleen stiffness measurement (SSM) with the same machine was found accurate to predict portal hypertension and esophageal varices. An SSM cutoff value <41.3 kPa is sensitive and seems able to accurately rule out the presence of varices. This supports a possible screening strategy, reserving upper endoscopy only for patients with an SSM ≥41.3kPa.

Study Type

Observational

Enrollment (Actual)

548

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Prince of Wales Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects will be recruited from the medical clinics of Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital. Patients with known chronic liver diseases, radiological evidence of liver cirrhosis and compensated liver function will be invited.

Description

Inclusion Criteria:

  • Age 18 years or above
  • Known chronic liver diseases
  • Radiological evidence of liver cirrhosis, defined as coarse liver echotexture and/or nodularity & small liver size noted on liver imaging
  • Informed written consent obtained

Exclusion Criteria:

  • Absence of chronic liver diseases (i.e. acute liver diseases in the absence of chronic components e.g. acute hepatitis A)
  • Decompensated liver cirrhosis, i.e. Child's B or C liver cirrhosis
  • Hepatocellular carcinoma
  • Portal vein thrombosis
  • Previous liver surgery
  • Liver transplantation
  • Recent upper endoscopy within last 36 months
  • Recent transient elastography within last 24 months
  • Current use of beta-blockers
  • Known varices of grade II or above diagnosed from previous endoscopic examination, and/or previous history of variceal bleeding
  • Previous endoscopic treatment to varices (e.g. banding ligation, sclerotherapy)
  • Serious concurrent illness (e.g. malignancy) leading to a life expectancy shorter than 6 months
  • Contraindications to transient elastography (e.g. pregnancy, previous pacemaker implantation)
  • Refusal to consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
LSSM arm
Intervention: upper endoscopy only performed to patients with high LSM (≥12.0kPa) or SSM (≥41.3kPa) values
Control arm
Intervention: upper endoscopy performed to all patients in this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinically significant esophageal and/or gastric varices
Time Frame: At time of upper endoscopy, up to 5 years

Number of participants who develop large varices warranting pharmacological and/or endoscopic therapy according to the indications mentioned below:

  • Varices of any size which is actively bleeding;
  • Varices of any size identified in the presence of blood in the esophagus and/or stomach;
  • Varices of any size with the presence of red-wale signs and/or fibrin plugs;
At time of upper endoscopy, up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Variceal bleeding
Time Frame: At last visit, up to 5 years
Number of participants who develop variceal bleeding, the diagnosis of which is made when diagnostic upper endoscopy shows one of the following: active bleeding from a varix, a "white nipple" overlying a varix, clots overlying a varix, or varices with no other potential source of bleeding.
At last visit, up to 5 years
hepatic events
Time Frame: At last visit, up to 5 years
Number of participants who develop ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatic decompensation to Child's B or C cirrhosis
At last visit, up to 5 years
Hospitalization
Time Frame: At last visit, up to 5 years
Number of participants who are admitted to hospital for emergency medical problems. This exclude hospitalizations which are scheduled electively.
At last visit, up to 5 years
Mortality
Time Frame: At last visit, up to 5 years
Number of participants who die because of any causes.
At last visit, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

December 12, 2013

First Submitted That Met QC Criteria

December 27, 2013

First Posted (Estimate)

December 31, 2013

Study Record Updates

Last Update Posted (Actual)

January 25, 2018

Last Update Submitted That Met QC Criteria

January 23, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LSSM-RCT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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