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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
SK Sharma, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier:
NCT00265226
First received: December 13, 2005
Last updated: January 3, 2014
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Biological: Intra-dermal administration of Mycobacterium w
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ministry of Science and Technology, India:

Primary Outcome Measures:
  • The time of sputum conversion as well as the early sputum conversion between the 2 groups will be evaluated. [ Time Frame: from baseline (visit 2) ] [ Designated as safety issue: Yes ]
  • The cure rate will be evaluated as the primary parameter of efficacy. [ Time Frame: 8-9 months ] [ Designated as safety issue: Yes ]
  • The relapse in patients of category II tuberculosis 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 ] [ Designated as safety issue: Yes ]
  • Recording of any clinical adverse reactions at anytime during the study for assessment of safety [ Time Frame: 2-8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • An additional secondary efficacy endpoint is the patient's and physician's global assessment of the clinical cure. [ Time Frame: 8-9 months ] [ Designated as safety issue: Yes ]

Enrollment: 1020
Study Start Date: March 2005
Study Completion Date: March 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category II ATT according to RNTCP guidelines
Biological: 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
Other Name: Immuvac
Placebo Comparator: 2
In this Arm patient will receive Placebo along with Category II ATT drugs according to RNTCP guidelines
Biological: 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
Other Name: Immuvac

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00265226

Locations
India
Mahavir Hospital
Hyderabad, Andhra Pradesh, India, 500004
All India Institute of Medical Sciences
New Delhi, Delhi, India, 110029
Lala Ram Swarup Institute of Tuberculosis and Respiratory Diseases
New Delhi, Delhi, India, 110030
Smt NHL Municipal Medical College & B.J. Medical College
Ahmedabad, Gujarat, India, 380006
National Tuberculosis Institute
Bangalore, Karnataka, India, 560 003
SMS Medical College
Jaipur, Rajasthan, India
Tuberculosis Research Centre
Chennai, Tamilnadu, India, 600 031
Central JALMA Institute of Leprosy
Agra, Uttar Pradesh, India, 282001
Sponsors and Collaborators
Ministry of Science and Technology, India
Investigators
Study Chair: Surendra K Sharma, M.D., Ph.D. Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
Study Director: Bindu Dey, Ph.D. Department of Biotechnology, MST, GOI
  More Information

Publications:

Responsible Party: SK Sharma, Professor and Head, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier: NCT00265226     History of Changes
Other Study ID Numbers: CR-01A/2003-10, NI-705
Study First Received: December 13, 2005
Last Updated: January 3, 2014
Health Authority: India: Ministry of Health

Keywords provided by Ministry of Science and Technology, India:
India
Pulmonary Tuberculosis
Category-II tuberculosis
Immunomodulator
Mycobacterium w
Revised National Tuberculosis Control Programme
Category-II Pulmonary Tuberculosis

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014