A New Screening Strategy for Varices

NCT02024347 | Completed

• 1 other identifier: LSSM-RCT
• Study Type: observational
• Target: 548
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Clinically significant esophageal and/or gastric varices

  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 Outcomes (4)

• Variceal bleeding

  At last visit, up to 5 years

• hepatic events

  At last visit, up to 5 years

• Hospitalization

  At last visit, up to 5 years

• Mortality

  At last visit, up to 5 years

Study Arms (2)

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.

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Related Publications (11)

• Vizzutti F, Arena U, Romanelli RG, Rega L, Foschi M, Colagrande S, Petrarca A, Moscarella S, Belli G, Zignego AL, Marra F, Laffi G, Pinzani M. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology. 2007 May;45(5):1290-7. doi: 10.1002/hep.21665.

  PMID: 17464971 BACKGROUND

• Castera L, Le Bail B, Roudot-Thoraval F, Bernard PH, Foucher J, Merrouche W, Couzigou P, de Ledinghen V. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009 Jan;50(1):59-68. doi: 10.1016/j.jhep.2008.08.018. Epub 2008 Oct 26.

  PMID: 19013661 BACKGROUND

• Bureau C, Metivier S, Peron JM, Selves J, Robic MA, Gourraud PA, Rouquet O, Dupuis E, Alric L, Vinel JP. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther. 2008 Jun;27(12):1261-8. doi: 10.1111/j.1365-2036.2008.03701.x. Epub 2008 Apr 4.

  PMID: 18397389 BACKGROUND

• Kazemi F, Kettaneh A, N'kontchou G, Pinto E, Ganne-Carrie N, Trinchet JC, Beaugrand M. Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol. 2006 Aug;45(2):230-5. doi: 10.1016/j.jhep.2006.04.006. Epub 2006 May 16.

  PMID: 16797100 BACKGROUND

• Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, Schiumerini R, Turco L, Di Biase AR, Mazzella G, Marzi L, Arena U, Pinzani M, Festi D. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012 Sep;143(3):646-654. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27.

  PMID: 22643348 BACKGROUND

• de Franchis R; Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010 Oct;53(4):762-8. doi: 10.1016/j.jhep.2010.06.004. Epub 2010 Jun 27. No abstract available.

  PMID: 20638742 BACKGROUND

• Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007 Sep;46(3):922-38. doi: 10.1002/hep.21907. No abstract available.

  PMID: 17879356 BACKGROUND

• de Franchis R, Pascal JP, Ancona E, Burroughs AK, Henderson M, Fleig W, Groszmann R, Bosch J, Sauerbruch T, Soederlund C, et al. Definitions, methodology and therapeutic strategies in portal hypertension. A Consensus Development Workshop, Baveno, Lake Maggiore, Italy, April 5 and 6, 1990. J Hepatol. 1992 May;15(1-2):256-61. doi: 10.1016/0168-8278(92)90044-p. No abstract available.

  PMID: 1506645 BACKGROUND

• Merkel C, Marin R, Angeli P, Zanella P, Felder M, Bernardinello E, Cavallarin G, Bolognesi M, Donada C, Bellini B, Torboli P, Gatta A; Gruppo Triveneto per l'Ipertensione Portale. A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis. Gastroenterology. 2004 Aug;127(2):476-84. doi: 10.1053/j.gastro.2004.05.004.

  PMID: 15300580 BACKGROUND

• Wong GL, Liang LY, Kwok R, Hui AJ, Tse YK, Chan HL, Wong VW. Low Risk of Variceal Bleeding in Patients With Cirrhosis After Variceal Screening Stratified by Liver/Spleen Stiffness. Hepatology. 2019 Sep;70(3):971-981. doi: 10.1002/hep.30522. Epub 2019 Mar 15.

  PMID: 30681726 DERIVED

• Wong GLH, Kwok R, Hui AJ, Tse YK, Ho KT, Lo AOS, Lam KLY, Chan HCH, Lui RA, Au KHD, Chan HLY, Wong VWS. A new screening strategy for varices by liver and spleen stiffness measurement (LSSM) in cirrhotic patients: A randomized trial. Liver Int. 2018 Apr;38(4):636-644. doi: 10.1111/liv.13560. Epub 2017 Sep 10.

  PMID: 28853196 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Grace LH Wong, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: December 31, 2013
• Study Start: July 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: January 25, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)