Efficacy & Safety of Pigtail Catheter Drainage Versus Need Based Thoracocentesis for Recurrent Hepatic Hydrothorax.

Study Overview
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Brief Summary
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In cirrhotic patients with recurrent hepatic hydrothorax liver transplantation is a definitive treatment. But a significant number of individual are ineligible for liver transplantation. In these patients to ameliorate the symptoms various treatment modalities such as TIPS, serial thoracocentesis, pigtail catheter drainage and pleurodesis are used. We are doing this study to assess the safety and efficacy of serial thoracocentesis verus pigtail catheter drainage.

Detailed Description
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Study population - Cirrhotic patients with recurrent hepatic hydrothorax Study design - A prospective, randomized, single center open label study Block Randomization, block size - 10 Sample size - Assuming in single time thoracocentesis group 5+/-3.67 thoracocentesis is required, investigator expect a 50 % reduction in pigtail drainage group. Apha error- 5, power -90, 15% dropout 35 patients in each arm Intervention - Group 1 - on-demand therapeutic thoracocentensis, Group 2 - small volume frequent thoracocentesis using PCD. Monitoring and assessment At enrollment: (A) Complete history and examination Etiology of cirrhosis Severity of ascites, Jaundice Prior Hepatic encephalopathy, bleed, Jaundice Prior Spontaneous bacterial peritonitis, large volume paracentesis frequency Pattern and number of prior decompensation Prior Acute on Chronic Liver Failure and Acute Kidney episodes Use of non selective beta blockers, norfloxaxin, rifaximin and albumin History of Endoscopic Variceal ligation or other endotherapy History of Hypertension, Diabetes Fever , signs of sepsis (SIRS) Examination- Sarcopenia, fraility, icterus, pedal edema At follow-up (at daily till Day - 7, thereafter at Day - 30 and Day 90) Complete history and examination Complications - SBP, SBE, ACLF and Jaundice, HE/ AKI episodes HTN, Diabetes control Fever , signs of sepsis (SIRS) Examination- Sarcopenia, fraility, icterus, pedal edema, ascites, HE Clinical Evaluation 1. Etiology of chronic liver disease (Baseline) 2. Severity of liver disease (Baseline, Day - 7, Day - 30, Day - 90 ) 3. MELD score, MELD-Na score, CTP score (Baseline, Day - 7, Day - 30, Day - 90 ) 4. Complications (Baseline, Day - 7, Day - 30, Day - 90 ) 5. Overt HE, PHT related Bleed, clinical jaundice, ascites, hyponatremia, AKI, SBP, Infection (specify site and severity), Frequency of Large Volume Paracentesis, On Demand Thoracocentesis Labs and follow up Baseline (at admission) - Blood : KFT, LFT, CBC, INR, AFP, PCT, S.PRA, Pro-BNP, Urinary Na Imaging : USG abdomen, X-ray chest, 2D ECHO Pleural fluid/ ascitic fluid - TLC, DLC, Protein, Sugar, SPAG, SAAG, ADA, c/s Hemodynamics : Intrapleural pressures at first TT Baseline (at randomization, Day -3 and Day - 7 in PCD-TT) - Blood : KFT, INR; S.PRA, Pro-BNP, Urinary Na (at Day 7) Imaging : X-ray chest Pleural fluid/ ascitic fluid - TLC, DLC, SPAG, c/s if indicated Day - 60, Day - 90 (end of follow-up) Blood : KFT, LFT, CBC, INR, AFP Imaging : USG abdomen, X-ray chest, 2D ECHO STATISTICAL ANALYSIS - Data will be reported as mean + SD. Categorical variables will be compared using the chi-square test or Fisher exact test Normal continuous variables will be compared using the Student's t test Non normal continuous variables will be compared using the Mann-Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data). The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox regression analysis will be performed to identify independent prognostic factors for survival. Univariate and multivariate analysis will be used whenever applicable. Adverse effects - Chest pain, pain at the site, Breathlessness, infection, pneumothorax, infection, bleeding Stopping rule - Liver Transplant Appearance of SBP, PICD, HE. Mortality End of follow-up

Official Title
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Efficacy & Safety of Pigtail Catheter Drainage Versus Need Based Thoracocentesis for Recurrent Hepatic Hydrothorax. A Randomized Controlled Trial

Conditions
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Hepatic Hydrothorax

Intervention / Treatment
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* Procedure: Large Volume Thoracocentesis
* Procedure: Pigtail Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years CLD with refilling symptomatic hepatic hydrothorax Exclusion Criteria: CTP >12, MELD>25 Tubercular PE, Ischemic cardiac disease If opting for TIPS/ LT Severe HPS Prior or current SBE/ SBP, septic shock Patients on mechanical ventilator Serum Creatinine >2 mg/dl Extrahepatic malignancy Serum Sodium < 120 Post TIPS/ BRTO/ SAE patients Post renal or liver transplantation Lack of informed consent Hepatocellular carcinoma outside milan criteria Non-cirrhotic portal HT Known HIV infection Pregnant women

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Large Volume Thoracocentesis<br>Group 1 - on-demand therapeutic thoracocentensis | Procedure: Large Volume Thoracocentesis<br>* Large Volume Thoracocentesis<br>|
| Active Comparator: Pigtail Catheter<br>Group 2 - small volume frequent thoracocentesis using PCD | Procedure: Pigtail Catheter<br>* Pigtail Catheter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Repeated Thoracocentesis |  | Day 30 | 
| Frequency of Repeated Thoracocentesis |  | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of refilling hydrothorax within |  | 72 hours | 
| Frequency of Repeated Thoracocentesis. |  | Day 30 and Day 90 | 
| Rate of Complete Response, Partial Response, No response. |  | Day 7, Day 30, Day 90 | 
| Number of times Thoracocentesis is required between both groups at Day 30 |  | Day 30 | 
| Number of times Thoracocentesis is required between both groups at Day 90 |  | Day 90 | 
| Proportion of pateint developing Post thoracocentesis Shock (Change in Heart Rate, Blood pressure) at Day 7 |  | Day 7 | 
| Proportion of pateint developing Post thoracocentesis Shock (Change in Heart Rate, Blood pressure) at Day 30 |  | Day 30 | 
| Proportion of pateint developing Post thoracocentesis Shock (Change in Heart Rate, Blood pressure) at Day 90 |  | Day 90 | 
| Change in Renal parameters - Serum Creatinine at Day 7 |  | Day 7 | 
| Change in Renal parameters - Serum Creatinine at Day 30 |  | Day 30 | 
| Change in Renal parameters - Serum Creatinine at Day 90 |  | Day 90 | 
| Hepatic encephalopathy: Grading as per West Haven Classification. | West Haven Grade (1-4) will be used to assess Hepatic Encephaloapthy, Grade 4 means worse outcome. | Day 7 | 
| Hepatic encephalopathy: Grading as per West Haven Classification. | West Haven Grade (1-4) will be used to assess Hepatic Encephaloapthy, Grade 4 means worse outcome. | Day 30 | 
| Hepatic encephalopathy: Grading as per West Haven Classification. | West Haven Grade (1-4) will be used to assess Hepatic Encephaloapthy, Grade 4 means worse outcome. | Day 90 | 
| Proportion of participants developing Na < 120 meg/l Day 7 |  | Day 7 | 
| Proportion of participants developing Na < 120 meg/l Day 30 |  | Day 30 | 
| Proportion of participants developing Na < 120 meg/l Day 90 |  | Day 90 | 
| Dose of Diuretic in each arm Day 7 |  | Day 7 | 
| Dose of Diuretic in each arm Day 30 |  | Day 30 | 
| Dose of Diuretic in each arm Day 90 |  | Day 90 | 
| Proportion of patient developing Spontaneous Bacterial Peritonitis at Day 7 |  | Day 7 | 
| Proportion of patient developing Spontaneous Bacterial Peritonitis at Day 30 |  | Day 30 | 
| Proportion of patient developing Spontaneous Bacterial Peritonitis at Day 90 |  | Day 90 | 
| Proportion of patients developing Spontaneous Bacterial Empyema Day 7 |  | Day 7 | 
| Proportion of patients developing Spontaneous Bacterial Empyema Day 30 |  | Day 30 | 
| Proportion of patients developing Spontaneous Bacterial Empyema Day 90 |  | Day 90 | 
| No. of days pateint surviving without Liver transplant and TIPS at Day 7 |  | Day 7 | 
| No. of days pateint surviving without Liver transplant and TIPS at Day 30 |  | Day 30 | 
| No. of days pateint surviving without Liver transplant and TIPS at Day 90 |  | Day 90 | 
| Incidence of Post procedure complications in between both groups at Day 7 |  | Day 7 | 
| Incidence of Post procedure complications in between both groups at Day 30 |  | Day 30 | 
| Incidence of Post procedure complications in between both groups at Day 90 |  | Day 90 | 
| Changes in MELD between the groups |  | Day 7 | 
| Changes in MELD between the groups |  | Day 30 | 
| Changes in MELD between the groups |  | Day 90 | 
| Changes in CTP between the groups |  | Day 7 | 
| Changes in CTP between the groups |  | Day 30 | 
| Changes in CTP between the groups |  | Day 90 | 
| Number of Episodes of Hospitalization between both groups at Day 7 |  | Day 7 | 
| Number of Episodes of Hospitalization between both groups at Day 30 |  | Day 30 | 
| Number of Episodes of Hospitalization between both groups at Day 90 |  | Day 90 | 
| Cumulative dose of albumin at D7 in two groups |  | Day 7 | 
| Cumulative dose of albumin at D30 in two groups |  | Day 30 | 
| Cumulative dose of albumin at D90 in two groups |  | Day 90 |