Efficacy of Antituberculous Therapy in Management of Sarcoidosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ritesh Agarwal, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT01245036
First received: November 15, 2010
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

From the time sarcoidosis has been described, there has always been a belief that the disease is in some way related to tuberculosis. If indeed tuberculosis is a causal factor in sarcoidosis, then the hypothesis can be further reinforced, if anti-tubercular therapy (ATT) is useful in treatment of sarcoidosis. Very few trials have been conducted in the past but the results of these trials have been discouraging. These trials were generally small studies and limited by time bias and used older regimens based on isoniazid, amino-salicylic acid and streptomycin. In our experience nearly one third of patients who are finally diagnosed to have sarcoidosis, have received ATT for variable length of time, but its impact of final outcome of sarcoidosis has not been studied. The aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of Rifampicin and Isoniazid along with prednisolone compared to prednisolone alone in treatment of Sarcoidosis.


Condition Intervention
Sarcoidosis
Tuberculosis
Drug: Antituberculous therapy along with steroids

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rifampicin and Isoniazid Along With Prednisolone Compared to Prednisolone Alone in Treatment of Sarcoidosis: a Pilot Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Postgraduate Institute of Medical Education and Research:

Primary Outcome Measures:
  • Remission rates [ Time Frame: Three months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse rates in the two groups [ Time Frame: six and 12 months after completion of treatment ] [ Designated as safety issue: Yes ]
  • Treatment related adverse effects in the two groups. [ Time Frame: Through out ] [ Designated as safety issue: Yes ]

Enrollment: 100
Study Start Date: January 2009
Study Completion Date: March 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glucocorticoid arm
Prednisolone 0.75 mg/kg/day for 6 weeks (maximum 60 mg) Prednisolone 0.5 mg/kg/day for 6 weeks (maximum 40 mg) Prednisolone 0.25 mg/kg/day for 6 months (maximum 20 mg) Taper over the next three months Prednisolone 0.25 mg/kg EOD for 15 days Prednisolone 0.125 mg/kg EOD for 15 days Then taper by 5 mg every 15 days to complete one year
Drug: Antituberculous therapy along with steroids
INH (300 mg/day) plus Rifampicin (450 mg/day if wt.<50 kg and 600 mg/day if wt. >50 kg) for six months Prednisolone 1 mg/kg/day for 6 weeks (maximum 80 mg) Prednisolone 0.75 mg/kg/day for 6 weeks (maximum 60 mg) Prednisolone 0.5 mg/kg/day for 3 months (maximum 40 mg) Prednisolone 0.25 mg/kg/day for 3 months (maximum 20 mg) Taper over the next three months Prednisolone 0.25 mg/kg EOD for 15 days Prednisolone 0.125 mg/kg EOD for 15 days Then taper by 5 mg every 15 days to complete one year

Detailed Description:

Sarcoidosis has evolved from the position of a disease of relative obscurity in the tropics, towards an increasing recognition and reporting from India and around. From the time sarcoidosis has been described, there has always been a belief that the disease is in some way related to tuberculosis. However, the inability to identify mycobacteria by histologic staining or culture from pathologic tissues continues to be one of the strongest arguments against a potential role for mycobacteria. Of late, molecular analysis (such as polymerase chain reaction [PCR] techniques) for nucleic acids of the putative agents serves as an alternative method for isolating fastidious organisms. A recent meta-analysis suggested a 30% prevalence rate of mycobacterial DNA in sarcoid samples but the individual studies reported detection rates from 0-50%. Moreover, most of these studies were published from countries with low prevalence for tuberculosis. If indeed mycobacteria are etiologically linked to sarcoidosis then the detection rates for mycobacterial DNA in sarcoid samples would be higher in countries with high prevalence of TB. In a recent prospective case-control study aimed at detection of mycobacterial DNA in patients with sarcoidosis from India, reinforced the hypothesis by showing mycobacterial DNA with PCR for 65 kDa protein gene in 48% of samples (BAL or biopsy) from freshly diagnosed patients of sarcoidosis.

There are numerous factors that favor mycobacteria being a trigger for sarcoidosis. These include histopathological appearances of the granulomas 15, reports of mycobacterial disease either existing coincidentally, succeeding or antedating sarcoidosis and the finding of mycobacteria in occasional granulomas of sarcoidosis.Passage experiments have also suggested that mycobacteria with characteristics of M. tuberculosis may be the incriminating agent.Recent studies on humoral immunity to mycobacterial antigens from sarcoidosis patients have renewed interest in a potential of mycobacteria in sarcoidosis. It has been shown that mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by known sarcoidosis susceptibility allele, DRB1*1101. It is possible that the presence of mycobacterial infection or BCG vaccination in genetically predisposed host may be involved in the development of autoimmunity.It has also been suggested that the organism might exist in a cell wall deficient L-form and may be difficult to isolate.

This possible link not only has implications in the differential diagnosis of the two common conditions, it may also have some therapeutic implications. Reactivation of tuberculosis after cortico-steroid treatment is instituted for sarcoidosis is a genuine concern, given the high prevalence of latent infection in our country. If indeed tuberculosis is a causal factor in sarcoidosis, then the hypothesis can be further reinforced, if anti-tubercular therapy (ATT) is useful in treatment of sarcoidosis. Very few trials have been conducted in the past but the results of these trials have been discouraging. These trials were generally small studies and limited by time bias and used older regimens based on isoniazid, amino-salicylic acid and streptomycin. In our experience nearly one third of patients who are finally diagnosed to have sarcoidosis, have received ATT for variable length of time, but its impact of final outcome of sarcoidosis has not been studied.

The aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of Rifampicin and Isoniazid along with prednisolone compared to prednisolone alone in treatment of Sarcoidosis.

  Eligibility

Ages Eligible for Study:   15 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

newly diagnosed sarcoidosis defined by presence of all of the following criteria:

  1. Presence with clinical features of pulmonary (dyspnea, dry cough, chest pain, fever, fatigue or crackles) or extra pulmonary organ (lymph nodes, liver, spleen, skin, eyes, heart, etc.) involvement and consistent radiological involvement and
  2. Compact non-caseating granulomas on trans-bronchial biopsy which are tissue AFB smear-negative

Exclusion Criteria:

Patients who have received glucocorticoid treatment before initial evaluation by us, or with presence of concomitant other cardio pulmonary disease will be excluded.

  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: NCT01245036

Locations
India
Deaprtment of Pulmonary Medicine, PGIMER
Chandigarh, India, 160012
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
Principal Investigator: Dheeraj Gupta PGIMER, Chandigarh
  More Information

No publications provided

Responsible Party: Ritesh Agarwal, Associate Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT01245036     History of Changes
Other Study ID Numbers: Sarc/Att/01
Study First Received: November 15, 2010
Last Updated: May 13, 2013
Health Authority: India: Dept of Pulmonary Medicine

Keywords provided by Postgraduate Institute of Medical Education and Research:
Sarcoidosis
Tuberculosis

Additional relevant MeSH terms:
Sarcoidosis
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Lymphatic Diseases
Lymphoproliferative Disorders
Mycobacterium Infections
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 20, 2014