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

• ClinicalTrials.gov Identifier: NCT06050837
• Recruitment Status: Not yet recruiting
• First Posted: September 22, 2023
• Last Update Posted: September 22, 2023
• Sponsor: Institute of Liver and Biliary Sciences, India
• Information provided by (Responsible Party): Institute of Liver and Biliary Sciences, India

Tracking Information

• First Submitted Date: September 16, 2023
• First Posted Date: September 22, 2023
• Last Update Posted Date: September 22, 2023
• Estimated Study Start Date: September 30, 2023
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 16, 2023): To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks [ Time Frame: 4 weeks ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 16, 2023)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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

  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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: High Risk Esophageal Varices

Intervention

Other: No intervention

No intervention

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 16, 2023): 130
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Dr Omkar Rudra, MD; 01146300000; omkar.rudra@gmail.com

• Listed Location Countries: India

Administrative Information

• NCT Number: NCT06050837
• Other Study ID Numbers: ILBS-SPARE-B-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Institute of Liver and Biliary Sciences, India
• Original Responsible Party: Same as current
• Current Study Sponsor: Institute of Liver and Biliary Sciences, India
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Institute of Liver and Biliary Sciences, India
• Verification Date: September 2023