Role of Ulinastatin in Preventing Severe Sepsis and Consequent Morbidities and Mortality

Study Overview
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Brief Summary
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The study will enhance the theory in the frame of reference on the efficacy of Ulinastatin while managing sepsis and subsequent morbidity and mortality. Moreover, the present study will explore Ulinastatin's prophylactic role in progression of multiple organ dysfunctions. Furthermore, the study will have the clinical implications in predicting the ICU admitted patient's stay and related cost in the context of new drug. Current researches will explore the new dimensions in Pakistan's healthcare facilities, paving the way of future academics to analyze it in order to enhance healthcare outcomes.

Detailed Description
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The current study is a randomised clinical trial with the aim of exploring the following objectives in the context of Pakistan: To determine the efficacy of Ulinastatin in preventing the progression of Sepsis to Severe Sepsis and septic shock. To assess the role of Ulinastatin in preventing the onset of MODS in sepsis-induced patients. To investigate the impact of Ulinastatin on sepsis associated mortality and morbidity. To explore the role of Ulinastatin in reducing ICU stays and associated costs in defined patients. To provides a condensed basis to understand ULINASTATIN as a sepsis management drug.

Official Title
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MUNI-SEP TRIAL-The Role of Ulinastatin in Preventing Severe Sepsis and Consequent Morbidities and Mortality; A Randomized Clinical Trial in Pakistan.

Conditions
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Severe Sepsis, Septic Shock, MODS

Intervention / Treatment
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* Drug: Ulinastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 or <60 Sepsis, and severe sepsis, as defined in operational definitions Patients voluntarily agreed to participate in the study after informed consent Exclusion Criteria: Fulminant hepatic failure Acute cerebrovascular accidents Acute poisoning Chronic Kidney Disease stage 5 Diagnosed case of immune thrombocytopenia Low output cardiac failure, with left ventricular ejection fraction <20% Advance chronic obstructive pulmonary disease on long term oxygen therapy Lactation or pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group Arm<br>Standard of care treatment arm, study medication will not be given | |
| Experimental: Active Intervention Arm<br>This group will receive Nine MiU Ulinastatin in three divided doses 8 hourly | Drug: Ulinastatin<br>* Nine MiU Ulinastatin in three divided doses 8 hourly for 3-5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of MOD's in patients with sepsis | To assess the role of Ulinastatin in preventing the onset of MODS in sepsis-induced patients. Sepsis is defnied as evidence of infection (positive culture of blood, Urine, Tracheal) or suspected infection (by a physician) plus 2 out of 4 criteria's of SIRS. MODS is presence of two or more organ dysfunction with scoring ≥2 of each organ as per Sequential Organ Failure Assessment (SOFA) score. | Day 1 of enrollment | 
| Prevention of MOD's in patients with sepsis | To assess the role of Ulinastatin in preventing the onset of MODS in sepsis-induced patients. Sepsis is defnied as evidence of infection (positive culture of blood, Urine, Tracheal) or suspected infection (by a physician) plus 2 out of 4 criteria's of SIRS. MODS is presence of two or more organ dysfunction with scoring ≥2 of each organ as per Sequential Organ Failure Assessment (SOFA) score. | Day 3 of enrollment | 
| Prevention of MOD's in patients with sepsis | To assess the role of Ulinastatin in preventing the onset of MODS in sepsis-induced patients. Sepsis is defnied as evidence of infection (positive culture of blood, Urine, Tracheal) or suspected infection (by a physician) plus 2 out of 4 criteria's of SIRS. MODS is presence of two or more organ dysfunction with scoring ≥2 of each organ as per Sequential Organ Failure Assessment (SOFA) score. | Day 5 of enrollment | 
| Effect on in-hospital mortality | To investigate the impact of Ulinastatin on sepsis associated mortality. | During first 48 hours of hospital stay after enrollment | 
| Effect on 7 days mortality | To investigate the impact of Ulinastatin on sepsis associated mortality. | During the 7 days of enrollment | 
| Effect on 14 days mortality | To investigate the impact of Ulinastatin on sepsis associated mortality. | During the 14 days of enrollment | 
| Effect on 28 days mortality | To investigate the impact of Ulinastatin on sepsis associated mortality. | During the 28 days of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days on mechanical ventilation | To explore the role of Ulinastatin in reducing the number of days on mechanical ventilation | Up to 28 days after enrollment | 
| Number of days in ICU | To explore the role of Ulinastatin in reducing ICU stays. | Up to 28 days after enrollment | 
| Prevention of Severe Sepsis in patients admitted with Sepsis | To determine the efficacy of Ulinastatin in preventing the progression of sepsis to severe sepsis. Severe sepsis is sepsis as defined above plus at least one organ/system dysfunction scoring ≥ 2 as per Sequential Organ Failure Assessment (SOFA) score. | Up to 28 days after enrollment | 
| Prevention of Septic Shock in patients admitted with Sepsis | To determine the efficacy of Ulinastatin in preventing the progression of sepsis to septic shock. Septic shock is persistent hypotension requiring vasopressors to maintain mean arterial pressure of 65mmHg or higher and a serum lactate level greater than 2mmol/L despite adequate volume resuscitation with 30ml/kg of crystalloid solution. | Up to 28 days after enrollment |