Effect of Midodrine on HVPG in Advanced Chronic Liver Disease

Study Overview
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Brief Summary
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Primary objective: HVPG response after administration of midodrine as defined by decrease in HVPG by > 20 % from baseline or to less than equals to 12 mmHg. Secondary objectives: Change in HVPG, SVR, heart rate, cardiac output, cardiac index, Blood pressure (systolic, diastolic and mean). Methodology: Consecutive patients of chronic liver disease in the Institute (admitted or coming to OPD) as per the inclusion and exclusion criteria will be studied. Study Population: Patients of advanced chronic liver disease admitted or OPD patients in ILBS Study Design: A single arm interventional study Study Period: 6 months Inclusion Criteria: i) CLD with grade III ascites with Na < 130 / Systolic BP < 90 / type 2 HRS(n=30 ) (ii) ACLF (APASL criteria) with Na < 130 / Systolic BP < 90 / AKI (n=30) Exclusion Criteria: age < 18 and > 75, pregnancy, splanchnic venous thrombosis, HCC, HE, significant cardiopulmonary disease, uncontrolled diabetes, hypertension, intrinsic renal disease, peripheral vascular disease. Sample Size with justification: This is a pilot study where a total of 60 patients will be enrolled - 30 each in the two groups. Intervention: HVPG will be done in these patients at baseline and then after 3 hours of 10 mg of midodrine tablets. Monitoring and assessment: Various parameters will be assessed during the procedure before and after 3 hours of midodrine such as HVPG (WHVP - FHVP), SVR, heart rate, cardiac output, cardiac index, Blood pressure (systolic, diastolic and mean), SpO2. - Statistical Analysis: Continuous data will be represented by mean ± SD or median ± IQR. Categorical data will be represented by n = frequency (%). Categorical data will be analyzed by Chi square test or Fisher exact test as appropriate. Continuous data will be compared by using student t test or Mann Whitney test (when applicable). The change in HVPG will be analyzed by using paired t test or Wilcoxon signed rank test. The % change in the individual group will be compared to see the significance between the groups. The significance will be seen at 5%. Adverse Effects: same as for HVPG (mild pain / hematoma at the puncture site, transient arrhythmias). Midodrine has got good safety profile and is used in patients of advanced chronic liver disease. Stopping Rule of study: nil Expected outcome of the project: If result shows that HVPG is decreased by midodrine, then it can be used in place of beta blockers when they are contraindicated or have the potential of causing adverse effects.

Official Title
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Effect of Midodrine on HVPG in Advanced Chronic Liver Disease - A Pilot Study

Conditions
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Chronic Liver Disease

Intervention / Treatment
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* Drug: Midodrine Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - i) CLD with grade III ascites with Na < 130 / Systolic BP < 90 / type 2 HRS(n=30 ) ii) ACLF (APASL criteria) with Na < 130 / Systolic BP < 90 / AKI (n=30) Exclusion Criteria: age < 18 and > 75, Pregnancy, Splanchnic venous thrombosis, Hepatocellular Carcinoma, Hepaticencephalopathy, Significant cardiopulmonary disease, Uncontrolled diabetes, Hypertension, Intrinsic renal disease, Peripheral vascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midodrine<br>Midodrine will be given 10 mg for one time only. HVPG will be done at baseline and after 3 hours | Drug: Midodrine Oral Tablet<br>* Midodrine will be given 10 mg for one time only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HVPG response after administration of midodrine as defined by decrease in HVPG by > 20 % from baseline or to less than equals to 12 mmHg |  | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hepatic Venous Pressure Gradient. |  | 3 hours | 
| Change in Systemic Vascular Resistance. |  | 3 hours | 
| Change in Heart Rate. |  | 3 hours | 
| Change in Cardiac Output. |  | 3 hours | 
| Change in Blood pressure (Systolic, Diastolic and Mean). |  | 3 hours | 
| Change in Cardiac Index. |  | 3 hours |