Comparative Study to assess efficacy and safety of Mycobacterium W. in Combination with Standard Therapy versus Standard Therapy Alone in treatment of Sepsis.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2015/07/005961
• Date of registration: 03-07-2015
• Prospective Registration: No
• Primary sponsor: Cadila Pharmaceuticals Limited
• Public title: Comparative Study to assess efficacy and safety of Mycobacterium W. in Combination with Standard Therapy versus Standard Therapy Alone in treatment of Sepsis.
• Scientific title: Randomized, Double blind, Two Arm, Comparative Controlled, Prospective Clinical Trial of Mycobacterium w in Combination with Standard Therapy versus Standard Therapy Alone in Sepsis due to Gram Negative Infection
• Date of first enrolment: 15-06-2015
• Target sample size: 150
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=8577
• Study type: Interventional
• Study design: Randomized, Parallel Group Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Pharmacy-controlled Randomization Blinding and masking:Participant and Investigator Blinded
• Phase: Phase 2/ Phase 3

Countries of recruitment

India

Contacts

• Name: Dr Arun Maseeh
• Affiliation: CRO-Cadila Pharmaceuticals Ltd

• Name: Dr Arun Maseeh
• Affiliation: CRO-Cadila Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria: 1. Any patient of severe sepsis or septic shock as defined below:

-Systemic Inflammatory Response Syndrome (SIRS): Two or more of the following conditions: temperature >38.5°C or <36.0°C; heart rate of >90 beats/min; respiratory rate of

>20 breaths/min or PaCO2 of <32 mm Hg; and WBC count of >12,000 cells/mL or <4000

cells/mL, or >10 percent immature (band) forms



-Sepsis: SIRS in response to presumed or documented infection (culture or Gram stain of

blood, sputum, urine, or normally sterile body fluid positive for pathogenic microorganism;

or focus of infection identified by visual inspection, e.g., ruptured bowel with free air or

bowel contents found in abdomen at surgery, wound with purulent discharge, consolidation

on chest radiograph).



-Severe sepsis: Sepsis and at least one of the following signs of organ hypoperfusion or organ

dysfunction: areas of mottled skin; capillary refilling of 3 s; urinary output of <0.5 mL/kg

for at least 1 h or renal replacement therapy; lactate >2 mmol/L; abrupt change in mental status or abnormal EEG findings; platelet count of <100,000 cells/mL or disseminated

intravascular coagulation; acute lung injury/ARDS; and cardiac dysfunction

(echocardiography)



-Septic shock: Severe sepsis and one of the following conditions:

Systemic mean BP of <60 mm Hg ( <80 mm Hg if previous hypertension) after 40 to 60

mL/kg saline solution, or PCWP between 12 and 20 mm Hg; and Need for dopamine of >5

mcg/kg/min, or norepinephrine or epinephrine of <0.25 mcg/kg/min to maintain mean BP at

>60 mm Hg (80 mm Hg if previous hypertension)



-Refractory septic shock: Need for dopamine at >15 mcg/kg/min, or nor-epinephrine or

epinephrine at >0.25 mcg/kg/min to maintain mean BP at >60 mm Hg (80 mm Hg if previous

hypertension



2. AND having at least one of the following:



-Source of Gram negative sepsis presumed to be originating from these sources

(gastrointestinal, hepatobiliary, genitourinary tract, pulmonary, neurological) or



-Documented by typical clinical signs and symptoms and confirmed by blood culture and/or

histology or



-Documented by typical clinical signs and symptoms and confirmed by CSF culture/tissue

culture and/or histology or



-Positive culture or histology confirmation or any other investigation deemed necessary must

be obtained at the time of enrolment and prior to the first dose of study medication



3. Patients and/or legally authorized representative(s), if applicable, have been fully informed and have given written informed consent. A patient unable to write and /or read but who fully understands the oral information given by the investigator (or nominated representative) has given oral informed consent witnessed in writing by an independent person.



4. Patients of either gender in the age range of 18-65 years



5. Female patients of child bearing potential must have a negative pregnancy test within 14 days prior to first dose of study medication. They must avoid becoming pregnant while receiving

study medication by maintaining adequate birth control practice



6. Patients must have sufficient venous access to permit administration of medication and

Exclusion criteria: 1. Blood culture is positive for Gram positive organism.



2. Patient is pregnant or nursing.



3. Patients whose sole diagnosis is fungal sepsis.



4. Patients with history of allergy, hypersensitivity, or any serious reaction to study medication.



5. Patient previously enrolled into this study.



6. Patient participating or having participated in a clinical trial with another investigational drug within the last 28 days except for investigational drugs against cancer, leukaemia or HIV.



7. Patients with a concomitant medical condition, whose participation, in the opinion of the investigator, may create an unacceptable additional risk.



8. Patients with a life expectancy judged to be less than five days from the basic disease other

than sepsis.



9. History of cardiopulmonary resuscitation for the current episode of sepsis



10. Patients not willing to participate or not likely to complete the trial as per judgement of the investigator.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Sepsis due to Gram Negative Infection Health Condition 2: A419- Sepsis, unspecified organism

Intervention(s)

Intervention1: MW and standard treatment of sepsis: single daily dose of 0.3 ml of Mw intra-dermal for 3 consecutive days and standard treatment of sepsis
Control Intervention1: Placebo of MW and standard treatment of sepsis: single daily dose of 0.3 ml of Mw-placebo intra-dermal for 3
consecutive days and standard treatment of sepsis

Primary Outcome(s)

efficacy of Mw in reducing mortality of patients with

sepsisTimepoint: 28 day

Secondary Outcome(s)

To study the effect of Mw on recovery of organ function as assessed by daily



SOFA scores



Ventilator free days



Time-to-vasopressor withdrawal



ICU length of stay

Hospital length of stay



Decline in inflammatory markers (IL-1, IL-2, TNF-, CRP, etc. at admission

and every 5 days till discharge/death)



To assess safety/tolerability by determining the incidence of adverse events in

the treatment group versus the control groupTimepoint: till 28 day or till discharge

Secondary ID(s)

PGI /0151 Version-02, dated 10/01/15

Source(s) of Monetary Support

Cadila Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date: 03/03/2012
Contact:

Institutional ethics Committee PGIMER

Status: Approved
Approval date: 13/12/2013
Contact:

ST. JOHNS MEDICAL COLLEGE & HOSPITAL INSTITUTIONAL ETHICS COMMITTEE

Status: Approved
Approval date: 30/06/2016
Contact:

Institutional Ethics Committee, PGIMS/UHS

Status: Approved
Approval date: 27/08/2016
Contact:

Institutional Ethics Committee - Clinical Studies

Status: Approved
Approval date: 22/05/2017
Contact:

SHIVAM ETHICS COMMITTEE

Status: Approved
Approval date: 22/05/2017
Contact:

Supe Hospital Ethics Committee

Status: Approved
Approval date: 05/07/2017
Contact:

Sumandeep Vidhyapeeth Institutional Ethics Committee

Status: Not Approved
Approval date:
Contact:

Institutional ethics Committee DMC & Hospital

Status: Not Approved
Approval date:
Contact:

Institutional ethics Committee PT. BDS PGIMS

Results

• Date Completed: 03/11/2018