MBT Versus HVPG in Identifying Responders to Portal Hypertension Therapy

Phase 1

Completed

• Conditions: Chronic Liver Disease; Bleeding; Cirrhosis; Esophageal Varices; Portal Hypertension
• Interventions: Device: Methacetin (with Breath testing device)

• Registration Number: NCT01851252
• Lead Sponsor: Meridian Bioscience, Inc.

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.

Study Timeline

• Study First Submitted: 2013-05-08
• Study First Submitted QC: 2013-05-09
• Study First Posted: 2013-05-10
• Study Start: 2013-10
• Primary Completion: 2017-08
• Study Completion: 2017-08
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-19
• Last Update Posted: 2022-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Methacetin (for BT) before / after Propanolol treatment.	Methacetin (with Breath testing device)	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.

Primary Outcome Measures

Name	Time	Method
The changes between MBT at baseline level and after chronic treatment in Propranolol	7 days	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	67 days	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.
Correlation between HVPG and MBT and their changes following the i.v. administration of Propranolol	7 days	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.

Trial Locations

Locations (1)

Carmel Medical Center; 🇮🇱 Haifa, Israel