Efficacy and Safety Study of Immunomodulator as an Adjunct Therapy in Pulmonary Tuberculosis (TB) Retreatment Patients

NCT ID: NCT00265226

Last Updated: 2014-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1020 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2011-03-31

Brief Summary

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The purpose of the study is to study the efficacy and safety of Mycobacterium in treating patients with lung tuberculosis . Mycobacterium is a strain of bacterium which is used as a vaccine and an adjuvant drug against leprosy. This agent has also been found to be effective in the treatment of lung tuberculosis in a limited number of patients.

The researchers are conducting this study in the World Health Organization (WHO) category-II of lung tuberculosis patients to see the efficacy and also to see any change in immunological parameters.

Detailed Description

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Mycobacterium w is a recently introduced immunomodulator, which has been found to be useful in rapid killing of Mycobacterium leprae. It improves the clearance of Mycobacterium leprae from the body and is thereby useful in reducing the duration of therapy significantly for multibacillary leprosy. Mycobacterium w shares an antigen with both Mycobacterium leprae as well as Mycobacterium tuberculosis. Mycobacterium w is also found to be useful in the prevention of tuberculosis in experimental animals.

Previous studies on the efficacy of Mycobacterium w as an immunomodulator in pulmonary tuberculosis patients have shown higher 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 0.5 x 10\^9 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 an intradermal injection, which contains 10\^9 bacilli. A total of 6 doses are given during the Intensive Phase (as per RNTCP, 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, Govt. of India) of treatment.

As of now, it is not commercially available for use in TB patients as an immunomodulator. Therefore, the investigators are investigating Mycobacterium w (Mw) for its efficacy in TB patients in a "double-blind placebo-controlled randomized clinical control trial" fashion. We are conducting this trial in Category-II pulmonary TB patients (as per RNTCP, 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.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

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

Group Type EXPERIMENTAL

Intra-dermal administration of Mycobacterium w

Intervention Type BIOLOGICAL

Mw Vaccine is given as oral suspension. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks

2

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

Group Type PLACEBO_COMPARATOR

Intra-dermal administration of Mycobacterium w

Intervention Type BIOLOGICAL

Mw Vaccine is given as oral suspension. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks

Interventions

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Intra-dermal administration of Mycobacterium w

Mw Vaccine is given as oral suspension. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks

Intervention Type BIOLOGICAL

Other Intervention Names

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Immuvac

Eligibility Criteria

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Inclusion Criteria

* Patients who are sputum positive for pulmonary tuberculosis and who have been treated previously for more than 1 month as per the RNTCP/WHO guidelines.
* Category II inclusion will mean all those patients who are Treatment after Default/Treatment Failure/Treatment Relapse.
* Patients who are willing to give written informed consent.

Exclusion Criteria

* Patients who are known to be hypersensitive to those ATTs being administered.
* Patients co-infected with HIV, hepatitis B or hepatitis C.
* Pregnant and lactating females or females of child bearing age with a urine HCG positive result 24-48 hours prior to every injection of Mw till 8 weeks.
* Patients with abnormal renal function, liver function or hematological tests.
* Seriously ill and moribund patients with complications such as low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive heart failure.
* Severely malnourished patients with body mass index (BMI) \< 15
* Severe hypoalbuminemia.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Science and Technology, India

OTHER_GOV

Sponsor Role lead

Responsible Party

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SK Sharma

Professor and Head

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Surendra K Sharma, M.D., Ph.D.

Role: STUDY_CHAIR

Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India

Bindu Dey, Ph.D.

Role: STUDY_DIRECTOR

Department of Biotechnology, MST, GOI

Locations

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Mahavir Hospital

Hyderabad, Andhra Pradesh, India

Site Status

Smt NHL Municipal Medical College & B.J. Medical College

Ahmedabad, Gujarat, India

Site Status

National Tuberculosis Institute

Bangalore, Karnataka, India

Site Status

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Site Status

Lala Ram Swarup Institute of Tuberculosis and Respiratory Diseases

New Delhi, National Capital Territory of Delhi, India

Site Status

SMS Medical College

Jaipur, Rajasthan, India

Site Status

Tuberculosis Research Centre

Chennai, Tamil Nadu, India

Site Status

Central JALMA Institute of Leprosy

Agra, Uttar Pradesh, India

Site Status

Countries

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India

References

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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.

Reference Type BACKGROUND
PMID: 15198421 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12408283 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7602215 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16038246 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10920614 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10920613 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10575405 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10575404 (View on PubMed)

Khatri GR, Frieden TR. Controlling tuberculosis in India. N Engl J Med. 2002 Oct 31;347(18):1420-5. doi: 10.1056/NEJMsa020098.

Reference Type BACKGROUND
PMID: 12409545 (View on PubMed)

Other Identifiers

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NI-705

Identifier Type: -

Identifier Source: secondary_id

CR-01A/2003-10

Identifier Type: -

Identifier Source: org_study_id

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