Clinical trial NCT00265226: Efficacy and Safety Study of Immunomodulator as an Adjunct Therapy in Pulmonary Tuberculosis (TB) Retreatment Patients
Official title: Efficacy and Safety Study of Immunomodulator (Mycobacterium w) as an Adjunct Therapy in Category-II Pulmonary Tuberculosis Along With Assessment of Immunological Parameters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tuberculosis
Keywords: India
Pulmonary Tuberculosis
Category-II tuberculosis
Immunomodulator
Mycobacterium w
Revised National Tuberculosis Control Programme
Category-II Pulmonary Tuberculosis
Lead sponsor: Ministry of Science and Technology, India
Sponsor class: OTHER_GOV
First posted: 2005-12-14
Enrollment: 1020
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The time of sputum conversion as well as the early sputum conversion between the 2 groups will be evaluated.
timeFrame: from baseline (visit 2)
measure: The cure rate will be evaluated as the primary parameter of efficacy.
timeFrame: 8-9 months
measure: The relapse in patients of category II tuberculosis will be compared in both the groups.
timeFrame: at an interval of 6, 12, 18 and 24 months after the completion of the therapy
measure: Recording of any clinical adverse reactions at anytime during the study for assessment of safety
timeFrame: 2-8 weeks
Secondary outcomes:
measure: An additional secondary efficacy endpoint is the patient's and physician's global assessment of the clinical cure.
timeFrame: 8-9 months
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Mahavir Hospital
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Lala Ram Swarup Institute of Tuberculosis and Respiratory Diseases
state: Delhi
city: Ahmedabad
country: India
facility: Smt NHL Municipal Medical College & B.J. Medical College
state: Gujarat
city: Bangalore
country: India
facility: National Tuberculosis Institute
state: Karnataka
city: Jaipur
country: India
facility: SMS Medical College
state: Rajasthan
city: Chennai
country: India
facility: Tuberculosis Research Centre
state: Tamilnadu
city: Agra
country: India
facility: Central JALMA Institute of Leprosy
state: Uttar Pradesh
Study officials:
affiliation: Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
name: Surendra K Sharma, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Department of Biotechnology, MST, GOI
name: Bindu Dey, Ph.D.
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
citation: Khatri GR, Frieden TR. Controlling tuberculosis in India. N Engl J Med. 2002 Oct 31;347(18):1420-5. doi: 10.1056/NEJMsa020098.