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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Esophageal Varices
• Intervention / Treatment: Other: No intervention

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

  1. CBC, RFT, LFT, PT/INR, vWF-Ag, HbA1c
  2. Collagen markers: Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid
  3. ECG
  4. 2D Echocardiography
  5. CECT Whole Abdomen
  6. Splenic stiffness measurement
  7. Liver stiffness measurement
  8. Upper GI endoscopy
  9. HVPG

• Investigations - performed at 1 month of maximum tolerable dose of Carvedilol

  1. CBC, RFT, LFT, PT/INR, vWF-Ag
  2. Collagen markers: Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid
  3. ECG
  4. Splenic stiffness measurement
  5. Liver stiffness measurement
  6. HVPG

• Adverse effects (of carvedilol)

  1. Allergy
  2. Light headedness
  3. Exercise intolerance
  4. Fatigue
  5. 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.

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Dr Omkar Rudra, MD; Phone Number: 01146300000; Email: omkar.rudra@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Omkar Rudra, MD; Phone Number: 01146300000; Email: omkar.rudra@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Cirrhosis of liver of different etiologies, with evidence of high-risk esophageal varices
3. Alcohol abstinence for 3 months
4. Written informed consent

Exclusion Criteria:

1. Age ≥ 70 years
2. Previous or imminent variceal ligation
3. Non Cirrhotic Portal Hypertension
4. Portal vein, splenic vein thrombosis
5. Porto-systemic shunts > 10 mm
6. Patients already on beta blockers

7. Contraindications to beta blocker therapy :

   1. Heart rate < 50 bpm
   2. Systolic BP < 100 mm Hg
   3. Severe COPD
   4. Atrioventricular block
   5. Known PVD
   6. Poor control of T2DM (HbA1c>9)
8. Technical difficulties for splenic stiffness measurement
9. Cardio-pulmonary disorders
10. Budd Chiari Syndrome
11. Grade 3 ascites
12. Acute Kidney Injury or Chronic Kidney Disease
13. Severely Obese patients (BMI > 40)
14. Pregnant women
15. Advanced HCC
16. Psychiatric Illness
17. Lack of informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2023
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 16, 2023
• First Submitted That Met QC Criteria: September 16, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 16, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension, Portal; Esophageal and Gastric Varices
• Other Study ID Numbers: ILBS-SPARE-B-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No