Mycobacterium w in Patients With Severe Sepsis

Study Overview
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Brief Summary
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Recent evidence suggests that sepsis continuum includes an immune paralytic state, which may play a significant role in sepsis. Mycobacterium w by its TLR4 agonist activity may help in restoring immunity, thereby improving outcomes in patients with severe sepsis. In this randomized trial, the investigators propose to evaluate the efficacy of Mw in patients with severe sepsis.

Official Title
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Phase IIb Randomized, Double Blind, Two Arm, Controlled Clinical Trial of Mycobacterium W in Combination With Standard Therapy Versus Standard Therapy Alone in Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Biological: Mycobacterium w
* Other: Best standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe sepsis within 48 hours of first organ dysfunction Cardiovascular system dysfunction: systolic blood pressure ≤90 mm Hg or the mean arterial pressure ≤70 mm Hg for at least one hour despite adequate fluid resuscitation or the use of vasopressors to maintain a systolic blood pressure or mean arterial pressure of >90 and >65 mm Hg, respectively Renal dysfunction: urine output <0.5 ml/kg/hour for two consecutive hours despite adequate fluid resuscitation Respiratory system dysfunction: PaO2/FiO2 ≤300 or ≤250 if lung sepsis Hematologic dysfunction: platelet count <100,000/mm3 or decrease by 50% in the three days preceding enrollment Unexplained metabolic acidosis: pH ≤7.30 Exclusion Criteria: Pregnancy Gram-positive culture Only fungal infection as source of sepsis Patients who received cardiopulmonary resuscitation Those on immunosuppressive therapy Those unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mycobacterium w group<br>Patients in the experimental arm (Mw) in addition to standard care will receive single daily dose of 0.3 mL of Mw (heat-inactivated Mw [0.5 × 10^9]; Cadila Pharma, Ahmedabad, India) in the deltoid region for 3 consecutive days | Biological: Mycobacterium w<br>* Single daily dose of 0.3 mL of Mw (heat-inactivated Mw [0.5 × 10^9]; Immuvac, Cadila Pharma, Ahmedabad, India) in the deltoid region for 3 consecutive days<br>Other: Best standard care<br>* Antibiotics as early as possible; Norepinephrine > vasopressin > epinephrine for hypotension; Blood glucose 140-180 mg/dL; DVT and stress ulcer prophylaxis; Low tidal volume mechanical ventilation; Standard VAP, CLABSI prevention bundles<br>|
| Active Comparator: Best standard care<br>Best standard care for sepsis | Other: Best standard care<br>* Antibiotics as early as possible; Norepinephrine > vasopressin > epinephrine for hypotension; Blood glucose 140-180 mg/dL; DVT and stress ulcer prophylaxis; Low tidal volume mechanical ventilation; Standard VAP, CLABSI prevention bundles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 28-day all-cause mortality | 28-day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New onset organ dysfunction measured by delta SOFA (maximum minus baseline SOFA) | Measured by delta SOFA (maximum minus baseline SOFA) | 28-day | 
| Ventilator-free days | Day off the mechanical ventilator | 28-day | 
| Time-to-vasopressor withdrawal |  | 28-day | 
| ICU length of stay |  | 28-day | 
| Hospital length of stay |  | 28-day | 
| New-onset infection |  | 28-day |