Spleen Stiffness as a Measure to Assess the REsponse to β Blocker Therapy (SPARE-B).
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks
Study Overview
Brief Summary
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
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
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
Outcomes
Primary Outcomes
To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks
Time Frame: 4 weeks
Secondary Outcomes
- Change in collagen markers - Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid(4 weeks)
- Change in Liver stiffness measurement(4 weeks)
- Change in Fib-4, Fib-5(4 weeks)
- Change in vWF-antigen, VITRO(4 weeks)
- To develop an AI based model to predict HVPG responders to beta blockers(4 weeks)