Mycobacterium w in Patients With Severe Sepsis (MISS)

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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Biological: Mycobacterium w; Other: Best standard care

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • UT
    • Chandigarh, UT, India, 160012
      • Department of Pulmonary Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mycobacterium w group; 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; 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; Other: Best standard care; 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
Active Comparator: Best standard care; Best standard care for sepsis	Other: Best standard care; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Collaborators: Pandit Bhagwat Dayal Sharma, PGIMS, Rohtak; St.John's National Academy of Health Sciences

Publications and helpful links

General Publications

• Sehgal IS, Agarwal R, Aggarwal AN, Jindal SK. A randomized trial of Mycobacterium w in severe sepsis. J Crit Care. 2015 Feb;30(1):85-9. doi: 10.1016/j.jcrc.2014.08.012. Epub 2014 Aug 28.
• Sehgal IS, Basumatary NM, Dhooria S, Prasad KT, Muthu V, Aggarwal AN, Pal A, Desai M, Chaudhry D, Supe PD, Kurmi P, Choudhuri R, Shah C, Agarwal R. A Randomized Trial of Mycobacterium w in Severe Presumed Gram-Negative Sepsis. Chest. 2021 Oct;160(4):1282-1291. doi: 10.1016/j.chest.2021.03.062. Epub 2021 May 7.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: December 26, 2014
• First Submitted That Met QC Criteria: December 31, 2014
• First Posted (Estimate): January 5, 2015

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: Pulm/Mw/002