Acute hemodynamiC Response To Carvedilol Predicts Survival in ACLF Patients

Acute hemodynamiC Response To Carvedilol Predicts Survival in ACLF Patients - "ACT - C ACLF Study

Clinically significant portal hypertension (CSPH) is defined as HVPG >10 mmHg. Patients with CSPH are at risk of developing esophageal varices and clinical decompensation (variceal bleeding, ascites, jaundice, encephalopathy), which mark the transition from compensated stage to a stage of the disease (decompensated) associated with higher mortality (1). HVPG is calculated by subtracting the free hepatic venous pressure (FHVP), a measure of systemic pressure, from the wedged hepatic venous pressure (WHVP), a measure of hepatic sinusoidal pressure. HVPG is surrogate marker in many clinical applications such as gold standard test to evaluate presence and severity of portal hypertension (PHT) diagnosis, risk stratification, monitoring of the patients on beta blockers (2). Non selective beta-blockers like propranolol and carvedilol are indicated in adults for primary and secondary prophylaxis of variceal hemorrhage. Acute hemodynamic response to intravenous propranolol with HVPG values coming down to <12 mm Hg or reduction to >20% from baseline have been shown to be associated with reduced long term risk of variceal bleed. Hence we are planning the current work to study the Acute hemodynamiC response To Carvedilol predicts survival in ACLF patients - "ACT - C ACLF study

Study Overview

• Status: Not yet recruiting
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Other: No intervention

Detailed Description

To assess whether Acute hemodynamic response to oral Carvedilol can predict short term outcome in ACLF patients.

• To determine the best cut off to define acute hemodynamic response in ACLF patients

Primary outcome - Predictive value of acute HVPG change by carvedilol for 28 day transplant free survival in patients of ACLF

Secondary outcome -

(1) Complications [PHT related bleed, AKI, infections, HE, Hypotension, Cardiac side effect] within 90 days (2) Transplant-free survival rate at 90 days (3) Correlation with evolution of AARC score by 2 week

(b) Methodology

Study population: Patients of age 18 to 70 years with ACLF fulfilling the conditions as per inclusion and exclusion criteria

Baseline parameters that will be recorded:

1. Baseline characteristics:
2. History and etiology of liver disease
3. Symptomatology, Evidence of decompensation (jaundice, encephalopathy, ascites, infections, variceal bleed etc)
4. Clinical and demographic profile
5. Endoscopy

Stopping rule of study:

1. Progression to exclusion criteria
2. In case of hypotension(<90/60mmHg) or Heart Rate <60 after carvedilol
3. Potential liver transplant within 90 days

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Dr Garvit Mundra, MD; Phone Number: 01146300000; Email: garvitmundrailbs@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Garvit Mundra, MD; Phone Number: 01146300000; Email: garvitmundrailbs@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients of age 18 to 70 years with ACLF fulfilling the conditions as per inclusion and exclusion criteria

Description

Inclusion Criteria:

1. Age 18-70 yrs
2. ACLF diagnosis (AARC criteria)

Exclusion Criteria:

1. Contraindications to NSBB (Heart rate < 65 /min, BP < 110/65 mm Hg, Asthma, Heart failure, AKI, Large ascites, SBP, S. Na < 125meq/l)
2. PVT
3. HCC
4. BCS
5. HE grades 2-4
6. NSBB therapy within 5 days
7. Pregnancy
8. Lactation
9. Planned for LT in the next 12 weeks
10. No consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Predictive value of acute HVPG change by carvedilol for 28 day transplant free survival in patients of ACLF	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Complications [PHT related bleed, AKI, infections, HE, Hypotension, Cardiac side effect] within 90 days	90 days
Transplant-free survival rate at 90 days	90 days
Correlation with evolution of AARC score by 2 week	2 week

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2024
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: ILBS-ACLF-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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