Clinical trial NCT06050837: 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).
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: High Risk Esophageal Varices
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2023-09-22
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: To evaluate the diagnostic accuracy of change in splenic stiffness to predict HVPG responders to beta-blockers at 4 weeks
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in Liver stiffness measurement
timeFrame: 4 weeks
measure: Change in Fib-4, Fib-5
timeFrame: 4 weeks
measure: Change in vWF-antigen, VITRO
timeFrame: 4 weeks
measure: Change in collagen markers - Procollagen 3 peptide, tissue inhibitor of matrix metalloproteinase 1, Hyaluronic acid
timeFrame: 4 weeks
measure: To develop an AI based model to predict HVPG responders to beta blockers
timeFrame: 4 weeks
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences
state: Delhi
Study officials:
References: