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MBT Versus HVPG in Identifying Responders to Portal Hypertension Therapy

Primary Purpose

Chronic Liver Disease, Cirrhosis, Esophageal Varices

Status
Completed
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
Methacetin (with Breath testing device)
Sponsored by
Meridian Bioscience, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chronic Liver Disease focused on measuring Cirrhotics, Esophageal varices, Portal Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

-> 18 years old (M/F)

-Diagnosis of cirrhosis: i. By liver biopsy ii. Or strong suspicion of cirrhosis by accepted criteria for the clinical diagnosis of cirrhosis (e.g. peripheral edema or varices, palpable hard left lobe of the liver, small right lobe span or palpable splenomegaly), and/or radiological evidence of cirrhosis (by abdominal US, CT, or MRI, showing a nodular liver and/or portosystemic collaterals with portal vein patency and/or ascites and/or splenomegaly, and/or colloid shift on a colloid-isotope liver-spleen scan), and/or laboratory variables (platelets <100,000/mm3, albumin< 3.5g/dL, or international normalized ratio (INR)>1.3) iii. Presence of esophageal varices (without previous variceal bleeding episode) or HVPG≥10mmHg 12mmHg from previous testing.

-Has been scheduled for hemodynamic study testing, including response to acute therapy.-

Exclusion Criteria:

  • Patients already receiving beta blockers
  • Hepatocellular carcinoma
  • Portal vein thrombosis
  • Contraindications to non-selective beta blocker Propanolol
  • Cholestatic liver disease
  • Severe heart, pulmonary or renal disease.
  • Patient has previous surgical bypass surgery for morbid obesity
  • Patient has extensive small bowel resection
  • Any major surgery in the past 3 months.
  • Patient is a recipient of any organ transplant
  • Patient allergic to acetaminophen.
  • Patients who are taking hepatotoxic drugs
  • Patient, based on the opinion of the investigator, should not be enrolled into this study.
  • Patients unable or unwilling to sign informed consent
  • Patients that are participating in other clinical trials evaluating experimental treatments or procedures or have participated in a clinical trial in the past 3 months.

Sites / Locations

  • Carmel Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Methacetin (for BT) before / after Propanolol treatment.

Arm Description

The methacetin breath test (MBT) will be performed before and after (within 2 hours) injection of Propanolol (BB) dose and once again after 60 days of oral administration of Propanolol.

Outcomes

Primary Outcome Measures

Correlation between HVPG and MBT and their changes following the i.v. administration of Propranolol
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
The changes between MBT at baseline level and after chronic treatment in Propranolol
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
MBT correlation to clinical events after 2 month of treatment
The MBT will be performed on subjects again after 60 days of oral beta blocker treatment and its results will be compared to previous MBT values.

Secondary Outcome Measures

Full Information

First Posted
May 8, 2013
Last Updated
December 19, 2022
Sponsor
Meridian Bioscience, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01851252
Brief Title
MBT Versus HVPG in Identifying Responders to Portal Hypertension Therapy
Official Title
Pilot Study to Evaluate the Correlation Between ¹³C Methacetin Breath Test (MBT) and HVPG Measurement as a Tool for Identifying Responders to Portal Hypertension Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
October 2013 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Meridian Bioscience, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the effect on the (carbon 13 labelled(13C)-Methacetin Breath Test (MBT) of i.v. propranolol, a non-selective beta blocker (NSBB) following initial administration and after chronic use of each of these agents. The correlation of the MBT with Hepatic Venous Pressure Gradient (HVPG) measurement before and after treatment will be assessed. Additionally, the MBT measurements following 60 days of therapy will be compared to the first MBT measurement and to the second MBT measurement, post HVPG. Each patient's subsequent MBT measurement will be compared to his previous MBT results in order to determine his/her response to therapy.
Detailed Description
Variceal bleeding is a life threatening complication of cirrhosis, which still carries a high mortality. Non selective beta-adrenergic blockers are effective at preventing first time variceal bleeding and re-bleeding. The efficacy of these drugs depends on the magnitude of reduction in portal pressure after administration, which varies widely between patients. Studies have shown that a reduction in portal pressure (as measured by HVPG) to 20% from baseline or to values ≤ 12 millimeters of mercury (mmHg) is associated with a low residual risk of bleeding . Patients with such a reduction are considered to be "responders" to beta blocker (BB) therapy. Unfortunately, a significant percentage of patients do not respond to therapy and need to be prescribed to an alternative therapy. The clinical application of this observation is limited since it requires a repeated HVPG measurement,which is not feasible in most cases. A non-invasive breath test that can assess portal pressure in correlation to HVPG and allow efficient management of patients at risk, could be very useful.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Liver Disease, Cirrhosis, Esophageal Varices, Portal Hypertension, Bleeding
Keywords
Cirrhotics, Esophageal varices, Portal Hypertension

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methacetin (for BT) before / after Propanolol treatment.
Arm Type
Experimental
Arm Description
The methacetin breath test (MBT) will be performed before and after (within 2 hours) injection of Propanolol (BB) dose and once again after 60 days of oral administration of Propanolol.
Intervention Type
Device
Intervention Name(s)
Methacetin (with Breath testing device)
Intervention Description
The methacetin is enriched with carbon 13, a stable non- radioactive isotope, and has been found to be safe in hundreds of studies. The material is very similar to acetominophen. 75 milligrams (mm) of this material pre- dissolved in water are used. This material undergoes rapid metabolism by the liver.
Primary Outcome Measure Information:
Title
Correlation between HVPG and MBT and their changes following the i.v. administration of Propranolol
Description
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
Time Frame
7 days
Title
The changes between MBT at baseline level and after chronic treatment in Propranolol
Description
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
Time Frame
7 days
Title
MBT correlation to clinical events after 2 month of treatment
Description
The MBT will be performed on subjects again after 60 days of oral beta blocker treatment and its results will be compared to previous MBT values.
Time Frame
67 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: -> 18 years old (M/F) -Diagnosis of cirrhosis: i. By liver biopsy ii. Or strong suspicion of cirrhosis by accepted criteria for the clinical diagnosis of cirrhosis (e.g. peripheral edema or varices, palpable hard left lobe of the liver, small right lobe span or palpable splenomegaly), and/or radiological evidence of cirrhosis (by abdominal US, CT, or MRI, showing a nodular liver and/or portosystemic collaterals with portal vein patency and/or ascites and/or splenomegaly, and/or colloid shift on a colloid-isotope liver-spleen scan), and/or laboratory variables (platelets <100,000/mm3, albumin< 3.5g/dL, or international normalized ratio (INR)>1.3) iii. Presence of esophageal varices (without previous variceal bleeding episode) or HVPG≥10mmHg 12mmHg from previous testing. -Has been scheduled for hemodynamic study testing, including response to acute therapy.- Exclusion Criteria: Patients already receiving beta blockers Hepatocellular carcinoma Portal vein thrombosis Contraindications to non-selective beta blocker Propanolol Cholestatic liver disease Severe heart, pulmonary or renal disease. Patient has previous surgical bypass surgery for morbid obesity Patient has extensive small bowel resection Any major surgery in the past 3 months. Patient is a recipient of any organ transplant Patient allergic to acetaminophen. Patients who are taking hepatotoxic drugs Patient, based on the opinion of the investigator, should not be enrolled into this study. Patients unable or unwilling to sign informed consent Patients that are participating in other clinical trials evaluating experimental treatments or procedures or have participated in a clinical trial in the past 3 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eyal Ashkenazi, M.D.
Organizational Affiliation
Carmel Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Carmel Medical Center
City
Haifa
ZIP/Postal Code
34362
Country
Israel

12. IPD Sharing Statement

Citations:
PubMed Identifier
12650802
Citation
Chalasani N, Kahi C, Francois F, Pinto A, Marathe A, Bini EJ, Pandya P, Sitaraman S, Shen J. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003 Mar;98(3):653-9. doi: 10.1111/j.1572-0241.2003.07294.x.
Results Reference
background
PubMed Identifier
15349904
Citation
Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy VG, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology. 2004 Sep;40(3):652-9. doi: 10.1002/hep.20339.
Results Reference
background
PubMed Identifier
16496319
Citation
Stokkeland K, Brandt L, Ekbom A, Hultcrantz R. Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969-2002. Hepatology. 2006 Mar;43(3):500-5. doi: 10.1002/hep.21089.
Results Reference
background
PubMed Identifier
15925423
Citation
de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005 Jul;43(1):167-76. doi: 10.1016/j.jhep.2005.05.009. No abstract available. Erratum In: J Hepatol. 2005 Sep;43(3):547.
Results Reference
background
PubMed Identifier
17681169
Citation
Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, Escorsell A, Garcia-Pagan JC, Makuch R, Patch D, Matloff DS, Bosch J; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007 Aug;133(2):481-8. doi: 10.1053/j.gastro.2007.05.024. Epub 2007 May 21.
Results Reference
background
PubMed Identifier
12668985
Citation
Abraldes JG, Tarantino I, Turnes J, Garcia-Pagan JC, Rodes J, Bosch J. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology. 2003 Apr;37(4):902-8. doi: 10.1053/jhep.2003.50133.
Results Reference
background
PubMed Identifier
16542287
Citation
Turnes J, Garcia-Pagan JC, Abraldes JG, Hernandez-Guerra M, Dell'Era A, Bosch J. Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis. Am J Gastroenterol. 2006 Mar;101(3):506-12. doi: 10.1111/j.1572-0241.2006.00453.x.
Results Reference
background
PubMed Identifier
2210246
Citation
Groszmann RJ, Bosch J, Grace ND, Conn HO, Garcia-Tsao G, Navasa M, Alberts J, Rodes J, Fischer R, Bermann M, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990 Nov;99(5):1401-7. doi: 10.1016/0016-5085(90)91168-6.
Results Reference
background
PubMed Identifier
7564785
Citation
Feu F, Garcia-Pagan JC, Bosch J, Luca A, Teres J, Escorsell A, Rodes J. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet. 1995 Oct 21;346(8982):1056-9. doi: 10.1016/s0140-6736(95)91740-3.
Results Reference
background
PubMed Identifier
11050041
Citation
Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Bellini B, Bighin R, Gatta A. The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology. 2000 Nov;32(5):930-4. doi: 10.1053/jhep.2000.19322.
Results Reference
background
PubMed Identifier
12447860
Citation
Bureau C, Peron JM, Alric L, Morales J, Sanchez J, Barange K, Payen JL, Vinel JP. "A La Carte" treatment of portal hypertension: Adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology. 2002 Dec;36(6):1361-6. doi: 10.1053/jhep.2002.36945.
Results Reference
background
PubMed Identifier
6609870
Citation
Bosch J, Groszmann RJ. Measurement of azygos venous blood flow by a continuous thermal dilution technique: an index of blood flow through gastroesophageal collaterals in cirrhosis. Hepatology. 1984 May-Jun;4(3):424-9. doi: 10.1002/hep.1840040312.
Results Reference
background
PubMed Identifier
10796880
Citation
Escorsell A, Bordas JM, Castaneda B, Llach J, Garcia-Pagan JC, Rodes J, Bosch J. Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension. Hepatology. 2000 May;31(5):1061-7. doi: 10.1053/he.2000.6779.
Results Reference
background
PubMed Identifier
3943775
Citation
Garcia-Tsao G, Grace ND, Groszmann RJ, Conn HO, Bermann MM, Patrick MJ, Morse SS, Alberts JL. Short-term effects of propranolol on portal venous pressure. Hepatology. 1986 Jan-Feb;6(1):101-6. doi: 10.1002/hep.1840060119.
Results Reference
background
PubMed Identifier
19501930
Citation
La Mura V, Abraldes JG, Raffa S, Retto O, Berzigotti A, Garcia-Pagan JC, Bosch J. Prognostic value of acute hemodynamic response to i.v. propranolol in patients with cirrhosis and portal hypertension. J Hepatol. 2009 Aug;51(2):279-87. doi: 10.1016/j.jhep.2009.04.015. Epub 2009 May 24.
Results Reference
background
PubMed Identifier
3500973
Citation
Valla D, Jiron MI, Poynard T, Braillon A, Lebrec D. Failure of haemodynamic measurements to predict recurrent gastrointestinal bleeding in cirrhotic patients receiving propranolol. J Hepatol. 1987 Oct;5(2):144-8. doi: 10.1016/s0168-8278(87)80565-2.
Results Reference
background
PubMed Identifier
16128681
Citation
Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Cavasin L, Gatta A. Disagreement between acute and chronic haemodynamic effects of nadolol in cirrhosis: a pathophysiological interpretation. Aliment Pharmacol Ther. 2005 Sep 1;22(5):433-9. doi: 10.1111/j.1365-2036.2005.02585.x.
Results Reference
background
PubMed Identifier
3610045
Citation
Vorobioff J, Picabea E, Villavicencio R, Puccini V, Rossi O, Bordato J, Audano M. Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients. Hepatology. 1987 Jul-Aug;7(4):648-53. doi: 10.1002/hep.1840070406.
Results Reference
background
PubMed Identifier
12447861
Citation
Banares R, Moitinho E, Matilla A, Garcia-Pagan JC, Lampreave JL, Piera C, Abraldes JG, De Diego A, Albillos A, Bosch J. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology. 2002 Dec;36(6):1367-73. doi: 10.1053/jhep.2002.36947.
Results Reference
background
PubMed Identifier
15679768
Citation
Braden B, Faust D, Sarrazin U, Zeuzem S, Dietrich CF, Caspary WF, Sarrazin C. 13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2005 Jan 15;21(2):179-85. doi: 10.1111/j.1365-2036.2005.02317.x.
Results Reference
background
PubMed Identifier
15609414
Citation
Festi D, Capodicasa S, Sandri L, Colaiocco-Ferrante L, Staniscia T, Vitacolonna E, Vestito A, Simoni P, Mazzella G, Portincasa P, Roda E, Colecchia A. Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels. World J Gastroenterol. 2005 Jan 7;11(1):142-8. doi: 10.3748/wjg.v11.i1.142.
Results Reference
background
PubMed Identifier
17593076
Citation
Goetze O, Selzner N, Fruehauf H, Fried M, Gerlach T, Mullhaupt B. 13C-methacetin breath test as a quantitative liver function test in patients with chronic hepatitis C infection: continuous automatic molecular correlation spectroscopy compared to isotopic ratio mass spectrometry. Aliment Pharmacol Ther. 2007 Jul 15;26(2):305-11. doi: 10.1111/j.1365-2036.2007.03360.x.
Results Reference
background
PubMed Identifier
11097497
Citation
de Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol. 2000 Nov;33(5):846-52. doi: 10.1016/s0168-8278(00)80320-7. No abstract available.
Results Reference
background
PubMed Identifier
17051449
Citation
Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis. 2006 Nov;26(4):348-62. doi: 10.1055/s-2006-951603.
Results Reference
background
PubMed Identifier
14767976
Citation
Groszmann RJ, Wongcharatrawee S. The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology. 2004 Feb;39(2):280-2. doi: 10.1002/hep.20062. No abstract available.
Results Reference
background
Links:
URL
http://www.ehow.com/how_7539959_measure-pressure-portal-vein.html
Description
How to measure the pressure of the portal vein

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MBT Versus HVPG in Identifying Responders to Portal Hypertension Therapy

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