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Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Intradermal injection of Mycobacterium w
Sponsored by
Ministry of Science and Technology, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring India, Pulmonary Tuberculosis, Category-I Pulmonary Tuberculosis, Immunomodulator, Mycobacterium w

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Patients of either sex aged between 18 to 60 yrs. Newly diagnosed sputum positive pulmonary TB cases with at least 2 sputum samples that are positive on sputum microscopy (Negative, Scanty, Scanty may be enrolled. Patients who are willing to give an informed consent. Exclusion Criteria Known hypersensitivity to Category I anti-TB drugs on history at the time of Screening. Known history of DR-TB (includes MDR-TB and XDR-TB) at the time of screening. Patients with Mtb isolate resistant to one or more drugs are to be excluded. Presence of secondary immunodeficiency states: HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids (illicited on detailed history and lab investigations). Hepatitis B and C positivity. Patients with known extrapulmonary TB and/or patients requiring surgical intervention. Currently receiving cytotoxic therapy, or have received it within the last 3 months- Ask on History. Pregnancy and lactation on history. Patients with a known seizure disorder on history. Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease on history. Patients with abnormal renal function (Serum creatinine more than 1.5 or proteinuria more than 2+ ) Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP more than 1.5 x ULN; PT = 1.3x control) Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3; platelets less than or equal to 100,000/mm3). Seriously ill and moribund patients with complications: low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive cardiac failure, BMI<15, severe hypoalbuminemia (< 2.5 g/dl). Patients unlikely to survive for less than 6 months. Patients unable to comply with the treatment regimen. Patients with history of alcohol or drug abuse- to be asked for on history and assessed using the CAGE Questions. The patient should be asked four questions in the following manner. A positive response to any of the following questions will be considered an exclusion criterion. i. Have you ever felt a need to CUT DOWN your drinking? ii. Have you ever felt ANGRY when confronted about the amount of alcohol you drink? iii. Have you ever felt GUILTY when confronted about the amount of alcohol you drink? iv. Have you ever felt the need to have a drink first thing in the morning? (EYE OPENER).

Sites / Locations

  • All India Institute of Medical Sciences
  • Central JALMA Institute of Leprosy and Other Mycobacterial Diseases

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category I ATT drugs according to RNTCP guidelines

In this Arm patient will receive Placebo along with Category I ATT drugs according to RNTCP guidelines

Outcomes

Primary Outcome Measures

The time of sputum conversion as well as the early sputum conversion between the two groups will be evaluated.
The cure rate will be evaluated as the primary parameter of efficacy.
The relapse in patients of category-I pulmonary TB will be compared in both the groups.
Recording of any clinical adverse reactions for assessment of safety.

Secondary Outcome Measures

An additional secondary efficacy endpoint is the patient's and physicians's global assessment of the clinical cure.

Full Information

First Posted
June 20, 2006
Last Updated
April 25, 2013
Sponsor
Ministry of Science and Technology, India
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1. Study Identification

Unique Protocol Identification Number
NCT00341328
Brief Title
Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.
Official Title
Efficacy and Safety of Immunomodulator (Mycobacterium w.) as an Adjunct Therapy in Category I Pulmonary Tuberculosis and Along With Assessment of Immunological Parameters
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ministry of Science and Technology, India

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of the study is to evaluate the efficacy and safety of Mycobacterium w in new lung tuberculosis patients. Mycobacterium w is a strain of bacterium which is being used as vaccine and adjunct drug against leprosy. This agent has also been found to be useful in the treatment of lung tuberculosis in limited number of patients. We are conducting this study in category-I patients( As per World Health Organization,Geneva classification of tuberculosis) having lung tuberculosis to see the efficacy and also to see any change in the immunological parameters.
Detailed Description
Mycobacterium w is a recently introduced immunomodulator ,which has been found to be useful in rapid killing of Mycobacterium leprae. It improves clearance of Mycobacterium leprae from body and is thereby useful in reducing duration of therapy significantly for multibacillary leprosy. Mycobacterium w shares antigens with Mycobacterium leprae as well as Mycobacterium tuberculosis. Mycobacterium w is also found to be useful in prevention of tuberculosis in experimental animals. Previous studies for efficacy of Mycobacterium w as immunomodulator in pulmonary tuberculosis patients have shown faster sputum conversion rates in patients given Mycobacterium w as an adjuvant therapy along with standard anti-tuberculosis treatment. It has faster and remarkable sputum converting capacity. Similar studies conducted in pulmonary TB category -II [Re-treatment as per Revised National Tuberculosis Control Programme (RNTCP), Govt. of India] patients have shown improved cure rates. Mycobacterium w is commercially available under the brand name of "Immuvac" injection in 0.5 ml multi-dose vials approved for use as immunomodulator against Mycobacterium leprae in patients with leprosy. Each vial has 500 million heat-killed bacilli in a buffered solution. It is manufactured by Cadila Pharmaceuticals Ltd.; Ahmedabad, Gujarat-382 210, India. In this clinical trial one dose consists of 0.1 ml given as intradermal injection, which contains 100 million bacilli. A total of 6 doses are given during the Intensive Phase(as per RNTCP,Ministry of Health and Family Welfare,Govt.of India) of treatment. Two injections on both upper arms on day-0 and subsequently one injection on days 14,28,42 and 56. No injections are given during the Continuation Phase(as per RNTCP,Ministry of Health and Family Welfare,Govt.of India)of treatment. As of now it is not commercially available for therapeutic use in TB patients as immunomodulator.Therefore we are investigating Mycobacterium w for its efficacy in TB patients in a "double-blind placebo-controlled randomized clinical control trial" fashion. We are conducting this trial in Category-I pulmonary TB Patients(as per RNTCP,Ministry of Health and Family Welfare,Govt.of India),and are assessing the outcome in the form of clinical improvement,sputum conversion and immunological parameters. This is a multi-centric trial sponsored by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India and Cadila Pharmaceuticals Ltd., India.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
India, Pulmonary Tuberculosis, Category-I Pulmonary Tuberculosis, Immunomodulator, Mycobacterium w

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category I ATT drugs according to RNTCP guidelines
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
In this Arm patient will receive Placebo along with Category I ATT drugs according to RNTCP guidelines
Intervention Type
Biological
Intervention Name(s)
Intradermal injection of Mycobacterium w
Other Intervention Name(s)
Immuvac
Intervention Description
Mw Vaccine is given as intradermal administration. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks
Primary Outcome Measure Information:
Title
The time of sputum conversion as well as the early sputum conversion between the two groups will be evaluated.
Time Frame
from the baseline(visit 2)
Title
The cure rate will be evaluated as the primary parameter of efficacy.
Time Frame
6-7 month
Title
The relapse in patients of category-I pulmonary TB will be compared in both the groups.
Time Frame
at an interval of 6,12,18 and 24 months after the completion of the therapy
Title
Recording of any clinical adverse reactions for assessment of safety.
Time Frame
at anytime during the study
Secondary Outcome Measure Information:
Title
An additional secondary efficacy endpoint is the patient's and physicians's global assessment of the clinical cure.
Time Frame
6-7 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients of either sex aged between 18 to 60 yrs. Newly diagnosed sputum positive pulmonary TB cases with at least 2 sputum samples that are positive on sputum microscopy (Negative, Scanty, Scanty may be enrolled. Patients who are willing to give an informed consent. Exclusion Criteria Known hypersensitivity to Category I anti-TB drugs on history at the time of Screening. Known history of DR-TB (includes MDR-TB and XDR-TB) at the time of screening. Patients with Mtb isolate resistant to one or more drugs are to be excluded. Presence of secondary immunodeficiency states: HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids (illicited on detailed history and lab investigations). Hepatitis B and C positivity. Patients with known extrapulmonary TB and/or patients requiring surgical intervention. Currently receiving cytotoxic therapy, or have received it within the last 3 months- Ask on History. Pregnancy and lactation on history. Patients with a known seizure disorder on history. Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease on history. Patients with abnormal renal function (Serum creatinine more than 1.5 or proteinuria more than 2+ ) Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP more than 1.5 x ULN; PT = 1.3x control) Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3; platelets less than or equal to 100,000/mm3). Seriously ill and moribund patients with complications: low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive cardiac failure, BMI<15, severe hypoalbuminemia (< 2.5 g/dl). Patients unlikely to survive for less than 6 months. Patients unable to comply with the treatment regimen. Patients with history of alcohol or drug abuse- to be asked for on history and assessed using the CAGE Questions. The patient should be asked four questions in the following manner. A positive response to any of the following questions will be considered an exclusion criterion. i. Have you ever felt a need to CUT DOWN your drinking? ii. Have you ever felt ANGRY when confronted about the amount of alcohol you drink? iii. Have you ever felt GUILTY when confronted about the amount of alcohol you drink? iv. Have you ever felt the need to have a drink first thing in the morning? (EYE OPENER).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Surendra K Sharma, MD, Ph.D.
Organizational Affiliation
Professor and Head,Department of Medicine, AIIMS, New Delhi-110029
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Bindu Dey, Ph.D.
Organizational Affiliation
Department of Biotechnology, MST, GOI
Official's Role
Study Director
Facility Information:
Facility Name
All India Institute of Medical Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110029
Country
India
Facility Name
Central JALMA Institute of Leprosy and Other Mycobacterial Diseases
City
Agra
ZIP/Postal Code
282001
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
15198421
Citation
Patel N, Trapathi SB. Improved cure rates in pulmonary tuberculosis category II (retreatment) with mycobacterium w. J Indian Med Assoc. 2003 Nov;101(11):680, 682.
Results Reference
background
PubMed Identifier
12408283
Citation
Patel N, Deshpande MM, Shah M. Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis. J Indian Med Assoc. 2002 Mar;100(3):191-3.
Results Reference
background
PubMed Identifier
7602215
Citation
Katoch K, Katoch VM, Natrajan M, Bhatia AS, Sreevatsa, Gupta UD, Sharma VD, Shivannavar CT, Patil MA, Bharadwaj VP. Treatment of bacilliferous BL/LL cases with combined chemotherapy and immunotherapy. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):202-12.
Results Reference
background
PubMed Identifier
16038246
Citation
Sharma P, Mukherjee R, Talwar GP, Sarathchandra KG, Walia R, Parida SK, Pandey RM, Rani R, Kar H, Mukherjee A, Katoch K, Benara SK, Singh T, Singh P. Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: clinical field trials with a follow up of 8-10 years. Lepr Rev. 2005 Jun;76(2):127-43.
Results Reference
background
PubMed Identifier
10575404
Citation
Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Disabilities in multibacillary leprosy following multidrug therapy with and without immunotherapy with Mycobacterium w antileprosy vaccine. Int J Lepr Other Mycobact Dis. 1999 Sep;67(3):250-8.
Results Reference
background
PubMed Identifier
10920614
Citation
Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine. Lepr Rev. 2000 Jun;71(2):193-205. doi: 10.5935/0305-7518.20000021.
Results Reference
background
PubMed Identifier
10920613
Citation
Sharma P, Misra RS, Kar HK, Mukherjee A, Poricha D, Kaur H, Mukherjee R, Rani R. Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after treatment. Lepr Rev. 2000 Jun;71(2):179-92. doi: 10.5935/0305-7518.20000020.
Results Reference
background
PubMed Identifier
10575405
Citation
Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine. Int J Lepr Other Mycobact Dis. 1999 Sep;67(3):259-69.
Results Reference
background
PubMed Identifier
12462334
Citation
Sharma SK, Mitra DK, Balamurugan A, Pandey RM, Mehra NK. Cytokine polarization in miliary and pleural tuberculosis. J Clin Immunol. 2002 Nov;22(6):345-52. doi: 10.1023/a:1020604331886.
Results Reference
background
PubMed Identifier
12409545
Citation
Khatri GR, Frieden TR. Controlling tuberculosis in India. N Engl J Med. 2002 Oct 31;347(18):1420-5. doi: 10.1056/NEJMsa020098.
Results Reference
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Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.

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