ADAMTS-13 LEVEL AS PREDICTIVE BIOMARKER FOR DEVELOPMENT OF PORTAL VEIN THROMBOSIS IN LIVER CIRRHOSIS (ADAPTHRO)

NCT03322696 | Unknown

• 1 other identifier: 0014168/17
• Study Type: observational
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with cirrhosis of viral etiology (HCV/HBV); Patients with cirrhosis of any other etiology (alcohol, idiopatic, autoimmune). Planned Number of cirrhotic subjects 200 patients Inclusion Criteria Subjects (18 yr old) with liver cirrhosis of any etiology, Exclusion Criteria All patients should not have hepatocellular carcinoma or other malignant tumors, they should not be treated with anticoagulant / antiplatelet agents, not affected by PVT already diagnosed and not suffering from congenital coagulation disorders (haemophilia A / B, von disease Willebrand, another congenital deficiency of coagulation factors) or severe thrombocytopenia (\<30,000 Plt / μL). Subject has participated in another clinical study within 30 days prior to study enrollment or is scheduled to participate in another clinical study on cirrhosis Primary Objective To describe the prospective modification of ADAMTS-13 level and other coagulation variables (e.g. FVIII, VWF:Ag/VWF:act) in cirrhotic patients during 18 months from the enrolment and to verify their predictive role as biomarker of development of portal vein thrombosis (PVT) Secondary Objectives To describe prospectively the modification of ADAMTS-13 level as a function of the etiology of cirrhosis Statistical analysis The total duration of the study will be of 12 months. The sample size of 200 subjects will be selected as a feasible number of patients to be recruited in a period of six months. The patients will be consecutively enrolled and followed for 18 months. As a result, in a follow up period of 18 months about 20-25 cases of PVT are expected. Continuous variables will be expressed as means ± standard deviations. In addition to descriptive statistics (location parameters), univariate analysis will be performed on each parameter and development of PVT during the follow up period. In previous observational studies both 1) a reduced PV flow \[prospectively\] and 2) a reduction of ADAMTS-13 are significantly associated with PVT. These associations will be investigated prospectively and analyzed simultaneously by a multivariate analysis and ROC curve to establish the sensitivity and specificity of these parameters as predictors of PVT development. Analyses will be performed using available data

Conditions

Liver Cirrhosis

Keywords

ADAMTS-13, Liver Cirrhosis, Portal Vein Thrombosis

Outcome Measures

Primary Outcomes (1)

• Association of portal vein thrombosis with ADAMTS13 activity

  Primary Endpoint To describe in a prospective way the association of both basal ADAMTS-13 level and portal vein flow with development of PVT in cirrhotic patients during 18 months from the enrolment. Measurement of ADAMTS-13 activity. ADAMTS-13 activity was measured in citrated plasma samples by a fluorescence resonance energy transfer (FRET)-based assay,

  18 months

Secondary Outcomes (1)

• Analysis of ADAMTS-13 and VWF levels as a function of the etiology of cirrhosis.

  18 months

Study Arms (1)

Cirr-PVT

Cirrhotic patients developing over 1 yr period thrombosis of portal vein or collaterals

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with liver cirrhosis of any etiology, diagnosed using imaging and/or histological criteria and observed in the Liver Unit of the "A. Gemelli" University will be included in this study.

You may qualify if:

• \- Patients with liver cirrhosis of any etiology, diagnosed using imaging and/or histological criteria and observed in the Liver Unit of the "A. Gemelli" University will be included in this study. All patients will sign an informed consent. The severity of liver function failure will be assessed using the Child-Pugh score \[11\]. Upper gastrointestinal endoscopy will be performed in all patients; the size of esophageal varices will be recorded as well as the presence of previous episodes of gastrointestinal bleeding. All the subjects will be outpatients and the time interval between the follow up visits will be approximately 120 days. The ultrasound criteria for the diagnosis of PVT will be the detection of echogenic material within one or more of the following vessels: portal trunk, right portal branch, left portal branch, splenic vein and superior mesenteric vein. Color and pulsed Doppler analysis will allow to confirm the diagnosis and to distinguish partial from complete obstructive thrombosis and in all cases the Doppler ultrasound diagnosis of PVT will be confirmed by contrast enhanced abdomen computed tomography. The presence and/or extension of the thrombosis to the other major vessels of the portal venous system (mesenteric or splenic vein) will registered in all patients. PVT will be classified according to the extension of thrombosis, as previously reported: grade I is referred to as portal thrombosis confined to the portal vein beyond the confluence of the splenic vein; grade II was a PVT extended to the superior mesenteric vein, but with patent mesenteric vessels; grade III is a PVT extended to the whole splanchnic venous system, but with large collaterals; grade IV is a thrombosis extended to the whole splanchnic venous system with only fine collaterals \[12\]. All the biochemical and coagulation parameters described below, including ADAMTS-13 and VWF levels, will be measured at each follow up visit.

Sponsors & Collaborators

• Raimondo De Cristofaro: lead

Study Sites (1)

Raimondo De Cristofaro

Roma, 00168, Italy

Location

Related Publications (13)

• Janssen HL, Meinardi JR, Vleggaar FP, van Uum SH, Haagsma EB, van Der Meer FJ, van Hattum J, Chamuleau RA, Adang RP, Vandenbroucke JP, van Hoek B, Rosendaal FR. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood. 2000 Oct 1;96(7):2364-8.

  PMID: 11001884 BACKGROUND

• Primignani M, Martinelli I, Bucciarelli P, Battaglioli T, Reati R, Fabris F, Dell'era A, Pappalardo E, Mannucci PM. Risk factors for thrombophilia in extrahepatic portal vein obstruction. Hepatology. 2005 Mar;41(3):603-8. doi: 10.1002/hep.20591.

  PMID: 15726653 BACKGROUND

• Parikh S, Shah R, Kapoor P. Portal vein thrombosis. Am J Med. 2010 Feb;123(2):111-9. doi: 10.1016/j.amjmed.2009.05.023.

  PMID: 20103016 BACKGROUND

• D'Amico M, Pasta F, Pasta L. Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population. Gene. 2015 Aug 15;568(1):85-8. doi: 10.1016/j.gene.2015.05.034. Epub 2015 May 16.

  PMID: 25987440 BACKGROUND

• Amitrano L, Guardascione MA, Ames PR, Margaglione M, Iannaccone L, Brancaccio V, Balzano A. Increased plasma prothrombin concentration in cirrhotic patients with portal vein thrombosis and prothrombin G20210A mutation. Thromb Haemost. 2006 Feb;95(2):221-3. doi: 10.1160/TH05-08-0555.

  PMID: 16493481 BACKGROUND

• Zoller B, Li X, Sundquist J, Sundquist K. Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med. 2011 Aug;270(2):158-65. doi: 10.1111/j.1365-2796.2010.02326.x. Epub 2010 Dec 3.

  PMID: 21129048 BACKGROUND

• Zocco MA, Di Stasio E, De Cristofaro R, Novi M, Ainora ME, Ponziani F, Riccardi L, Lancellotti S, Santoliquido A, Flore R, Pompili M, Rapaccini GL, Tondi P, Gasbarrini GB, Landolfi R, Gasbarrini A. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol. 2009 Oct;51(4):682-9. doi: 10.1016/j.jhep.2009.03.013. Epub 2009 Apr 23.

  PMID: 19464747 BACKGROUND

• Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A, Di Maurizio L, Bombardieri G, De Cristofaro R, De Gaetano AM, Landolfi R, Gasbarrini A. Portal vein thrombosis: insight into physiopathology, diagnosis, and treatment. World J Gastroenterol. 2010 Jan 14;16(2):143-55. doi: 10.3748/wjg.v16.i2.143.

  PMID: 20066733 BACKGROUND

• Uemura M, Tatsumi K, Matsumoto M, Fujimoto M, Matsuyama T, Ishikawa M, Iwamoto TA, Mori T, Wanaka A, Fukui H, Fujimura Y. Localization of ADAMTS13 to the stellate cells of human liver. Blood. 2005 Aug 1;106(3):922-4. doi: 10.1182/blood-2005-01-0152. Epub 2005 Apr 26.

  PMID: 15855280 BACKGROUND

• Lancellotti S, Basso M, Veca V, Sacco M, Riccardi L, Pompili M, De Cristofaro R. Presence of portal vein thrombosis in liver cirrhosis is strongly associated with low levels of ADAMTS-13: a pilot study. Intern Emerg Med. 2016 Oct;11(7):959-67. doi: 10.1007/s11739-016-1467-x. Epub 2016 May 24.

  PMID: 27220954 BACKGROUND

• Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646-9. doi: 10.1002/bjs.1800600817. No abstract available.

  PMID: 4541913 BACKGROUND

• Yerdel MA, Gunson B, Mirza D, Karayalcin K, Olliff S, Buckels J, Mayer D, McMaster P, Pirenne J. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation. 2000 May 15;69(9):1873-81. doi: 10.1097/00007890-200005150-00023.

  PMID: 10830225 BACKGROUND

• Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol. 2005 Apr;129(1):93-100. doi: 10.1111/j.1365-2141.2005.05420.x.

  PMID: 15801961 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Raimondo De Cristofaro, MD

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 26, 2017
• Study Start: October 1, 2017
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: November 12, 2020

Record last verified: 2020-11

Locations

IT (1)