Effect of Midodrine on HVPG in Advanced Chronic Liver Disease

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

• 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.

Study Overview

• Status: Completed
• Conditions: Chronic Liver Disease
• Intervention / Treatment: Drug: Midodrine Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. age < 18 and > 75,
2. Pregnancy,
3. Splanchnic venous thrombosis,
4. Hepatocellular Carcinoma,
5. Hepaticencephalopathy,
6. Significant cardiopulmonary disease,
7. Uncontrolled diabetes,
8. Hypertension,
9. Intrinsic renal disease,
10. Peripheral vascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2020
• Primary Completion (Actual): December 13, 2021
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: ILBS-Cirrhosis-33

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