Spleen Stiffness as a Measure to Assess the REsponse to β Blocker Therapy (SPARE-B)

Study Overview
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Brief Summary
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HVPG is the gold standard for measurement of the presence and severity of portal hypertension. Clinically Significant Portal Hypertension (CSPH) is defined as HVPG ≥ 10 mmHg. Reducing the HVPG by use of non-selective beta blockers has been associated with reduced risk of variceal hemorrhage, ascites, SBP and thus has a positive effect on survival. Response to Beta blocker therapy is defined as a reduction of HVPG by 10% or to ≤ 12 mmHg. HVPG is an invasive method of assessment of portal pressures, with lack of availability at many centres. While non-invasive tests to predict CSPH have been defined, predicting response to beta-blockers non-invasively is an unmet clinical need. The aim of this study is to use splenic stiffness measurement, a non-invasive test, as a surrogate to assess the response of HVPG to beta blocker therapy.

Detailed Description
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Aim and Objective: To evaluate change in splenic stiffness measurement as a surrogate for response to non-selective beta blockers in patients with high-risk esophageal varices. Primary objectives: To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks - Study population: All patients aged ≥ 18 years and ≤ 70 years presenting to Institute of Liver and Biliary Sciences, New Delhi with high-risk esophageal varices upon presentation and are giving written consent for participation in the study. Study design - Single center, Prospective, observational study. Study period - 1 year Sample size - We are enrolling 130 patients in the study Intervention - Carvedilol will be initiated to all patients with high-risk esophageal varices (in the absence of any contraindications) at a dose of 3.125mg BD and titrated to the maximum tolerable dose within 7 days. Monitoring and assessment - Investigations - performed at Baseline CBC, RFT, LFT, PT/INR, vWF-Ag, HbA1c Collagen markers: Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid ECG 2D Echocardiography CECT Whole Abdomen Splenic stiffness measurement Liver stiffness measurement Upper GI endoscopy HVPG Investigations - performed at 1 month of maximum tolerable dose of Carvedilol CBC, RFT, LFT, PT/INR, vWF-Ag Collagen markers: Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid ECG Splenic stiffness measurement Liver stiffness measurement HVPG Adverse effects (of carvedilol) Allergy Light headedness Exercise intolerance Fatigue Chest tightness Stopping rule - Development of variceal bleed Expected outcome of the project: Change in splenic stiffness will correlates with change in HVPG and can reliably predict response to non-selective beta blockers in patient with high-risk esophageal varices.

Official Title
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Spleen Stiffness as a Measure to Assess the REsponse to β Blocker Therapy (SPARE-B).

Conditions
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High Risk Esophageal Varices

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Cirrhosis of liver of different etiologies, with evidence of high-risk esophageal varices Alcohol abstinence for 3 months Written informed consent Exclusion Criteria: Age ≥ 70 years Previous or imminent variceal ligation Non Cirrhotic Portal Hypertension Portal vein, splenic vein thrombosis Porto-systemic shunts > 10 mm Patients already on beta blockers Contraindications to beta blocker therapy : Heart rate < 50 bpm Systolic BP < 100 mm Hg Severe COPD Atrioventricular block Known PVD Poor control of T2DM (HbA1c>9) Technical difficulties for splenic stiffness measurement Cardio-pulmonary disorders Budd Chiari Syndrome Grade 3 ascites Acute Kidney Injury or Chronic Kidney Disease Severely Obese patients (BMI > 40) Pregnant women Advanced HCC Psychiatric Illness Lack of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No intervention|No intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Liver stiffness measurement |  | 4 weeks | 
| Change in Fib-4, Fib-5 |  | 4 weeks | 
| Change in vWF-antigen, VITRO |  | 4 weeks | 
| Change in collagen markers - Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid |  | 4 weeks | 
| To develop an AI based model to predict HVPG responders to beta blockers |  | 4 weeks |