Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients.

Study Overview
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Brief Summary
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The patients with ACLF having Ascites who require ascitic tapping will undergone ascitic tapeither under albumin cover alone or with midodrine. The patient will be monitored for complication and changes of PICD. Study analysis will be done with primary objective being reduction in incidence of PICD.

Detailed Description
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OBJECTIVE: Primary objective: Incidence of Paracentesis induced circulatory dysfunction in patients undergoing modest volume paracentesis (MVP) (>3 and <5 litres) with midodrine plus 25% albumin v/s 25% albumin infusion alone at day 7 Secondary objective: Change in systolic, diastolic and mean BP at day 3 and 6 Increase in plasma renin activity at day 6 Incidence of Hyponatremia, HE and AKI at day 3 and 6 Predictors of Paracentesis induced circulatory dysfunction Predictors of 28 day survival. Methodology : Patients with Acute on chronic liver failure having grade III ascites will be given either albumin or albumin plus midodrine. Midodrine will be started 4 hrs before tap to achieve target MAP. Ascitic tapping will be followed by vital monitoring and monitoring of vital parameters along with measurement of changes in s. rennin at day 3 and 6. All patient will be undergo complete physical examination and complete clinical history will be recorded. Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin levels Those eligible will be randomised in to two groups GROUP A will be given albumin 8g/l of ascitic tap during tap along with placebo for 7 days. GROUP B will be given midodrine 7.5 mg to 12.5 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group. Study Population: Patients of acute on chronic liver failure who are admitted to and attending the OPD at ILBS. Study Design: Randomized controlled trial Study Period:NOV 2019 to march 2019 Sample Size: Considering incidence of PICD in albumin group is 30% and reduction to 10% by adding midodrine with alpha =5%, and power of study being 80%. No. of cases in each group- 66 Total-132 Furthur with 10% dropout we need to enroll 150 cases (75 in each group) randomly allocated in two groups by block randomization method with block size of 5. Intervention: This RCT will be conducted at ILBS New Delhi between Dec 2019 and March 2021 Monitoring and assessment: All patient will be undergo complete physical examination and complete clinical history will be recorded. Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin levels Those eligible will be randomised in to two groups GROUP A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week) GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group. Expected outcome of the project: Primary: Incidence of PICD at day 3 and day6 Secondary: Changes in hemodynamic parameters at 1, 3 and 6 hour, Day 3, Day 6 post paracentesis Increase in plasma renin activity at Day 3, Day 6 Incidence of Hyponatremia, HE and AKI at day 3 and 6

Official Title
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Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients-A Randomized Controlled Trial.

Conditions
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Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Biological: Albumin
* Drug: Midodrine Oral Tablet
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - ACLF patients (as per APASL definition) with grade II/III ascites Exclusion Criteria: Age < 18 or >75 years Hepatocellular carcinoma Extrahepatic portal vein obstruction Non cirrhotic ascites Serum creatinine >1.5mg/dl Refractory septic shock Beta blockersPortal vein thrombosis Grade 3-4 HE Pregnancy or Lactation Active variceal bleed Respiratory, cardiac, renal failure Uncontrolled hypertension Severe coagulopathy Refusal to participate

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albumin with placebo<br>Group A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week) | Biological: Albumin<br>* Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week)<br>Other: Placebo<br>* Placebo<br>|
| Experimental: Albumin with Midodrine<br>GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group. | Biological: Albumin<br>* Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week)<br>Drug: Midodrine Oral Tablet<br>* Midodrine 7.5 mg to 10 mg TDS (keeping the target MAP above 70 mmHg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of PICD (Paracentesis Induced Circulatory Dysfunction) |  | Day 3 | 
| Incidence of PICD (Paracentesis Induced Circulatory Dysfunction) |  | Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Mean Arterial Pressure (MAP) post paracentesis. |  | 1 hour | 
| Changes in Heart Rate post paracentesis. |  | 1 hour | 
| Changes in Mean Arterial Pressure (MAP) post paracentesis. |  | 3 hours | 
| Changes in Heart Rate post paracentesis. |  | 3 hours | 
| Changes in Mean Arterial Pressure (MAP) post paracentesis. |  | 6 hours | 
| Changes in Heart Rate post paracentesis. |  | 6 hours | 
| Changes in Mean Arterial Pressure (MAP) post paracentesis. |  | Day 3 | 
| Changes in Heart Rate post paracentesis. |  | Day 3 | 
| Changes in Mean Arterial Pressure (MAP) post paracentesis. |  | Day 6 | 
| Changes in Heart Rate post paracentesis. |  | Day 6 | 
| Change in plasma renin activity in both groups |  | Day 3 | 
| Change in plasma renin activity in both groups |  | Day 6 | 
| Incidence of Hyponatremia in both groups |  | Day 3 | 
| Incidence of Hyponatremia in both groups |  | Day 6 | 
| Incidence of Hepatic Encephalopathy in both groups |  | Day 3 | 
| Incidence of Hepatic Encephalopathy in both groups |  | Day 6 | 
| Incidence of Acute Kidney Injury in both groups |  | Day 3 | 
| Incidence of Acute Kidney Injury in both groups |  | Day 6 |