Clinical trial NCT01560078: Efficacy Study of Thrice Weekly Directly Observed Treatment Short-Course Regimen in Tubercular Pleural Effusion
Official title: Evaluation of Efficacy of Thrice Weekly DOTS Regimen in Tubercular Pleural Effusion at 6 Months
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Pleural Effusion
Keywords: Tuberculosis
Pleural effusion
Category 3
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Sri Venkateswara Institute of Medical Sciences University
First posted: 2012-03-22
Enrollment: 360
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1042 patients presenting with unilateral tubercular pleural effusion who attended DOTS Centres/Chest clinics at the respective Study sites between the ages 15 and 65 years were screened for the study.351 were enrolled after 691 were excluded due to various reasons.

Brief summary: Tubercular pleural effusion is the second most common form of extrapulmonary tuberculosis (EPTB) seen in clinical practice after tuberculosis (TB) lymphadenitis. It is common that after complete treatment of the patient with tubercular pleural effusion with six months of the short-course chemotherapy under Directly Observed Treatment Short-Course (DOTS), pleural effusion has not resolved completely. In these cases treatment need to be extended for one or two more months by giving extension pouches.

Since DOTS does not recommend demonstration of complete resolution of tubercular pleural effusion at the end of treatment completion, there is paucity of data in terms of the patients declared cure for the sputum negative pulmonary and extra-pulmonary TB as such which includes TB pleural effusion as well. This project aims to look into the patient characteristics, treatment outcome, and compute the number of cases which require an extended regimen and to what extent is the pleural effusion persistent at the end of six months of standard DOTS therapy.

Detailed description: India's Revised National Tuberculosis Control Programme (RNTCP), based on Directly Observed Treatment Short-Course (DOTS) strategy, began as a pilot project in 1993 and was launched as a national program in 1997. Three categories of treatment were recommended based on disease characteristics. Category III regimen comprised of thrice-weekly isoniazid, rifampicin and pyrazinamide in the intensive phase; with isoniazid and rifampicin in the continuation phase. This regimen was recommended for sputum smear negative and extrapulmonary tuberculosis (TB) patients who were not seriously ill. The omission of ethambutol in non-cavitary, smear-negative pulmonary TB patients who were known to be human immunodeficiency virus (HIV) negative was endorsed by the World Health Organization (WHO) guidelines. However, in view of high level of initial resistance to isoniazid in many areas, recent guidelines recommend adding ethambutol in the intensive phase, effectively eliminating category III.

This study was designed as a multicentre, longitudinal observational study and was carried out between 2006 and 2011. Three hundred and sixty patients were planned to be enrolled across 4 centres, namely AIIMS (New Delhi), SMS Medical College (Jaipur), SVIMS (Tirupati) and BJ Medical College (Ahmedabad); i.e. 90 patients at each centre. Lost to follow-up/default rate of 12% was expected in the study. Recruitment was done from the study sites directly as well as from referrals via nearby DOTS centres, hospitals and chest clinics.

Eligibility criteria: Inclusion Criteria:

* Patients with unilateral TB pleural effusion \< 1500 ml

Exclusion Criteria:

* Patients \< 15 years and \> 65 years were excluded
* Patients with opacity greater than four intercostal spaces in the posteroanterior (PA) chest radiograph
* Bilateral pleural effusion
* Patients who were failures/defaulters/relapses (eligible for cat II as per RNTCP guidelines)
* Sputum-smear positive cases, miliary TB, moderately advanced and far advanced parenchymal involvement on chest radiograph (eligible for cat I)
* HIV positive
* Hepatitis B surface antigen (HBsAg) positive
* Diabetes mellitus
* Refusing thoracocentesis
* Evidence of empyema
* Residence outside the study area
* Refuse to give consent

Primary outcomes:
measure: Complete resolution of pleural effusion on ultrasonogram
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
Study officials:
affiliation: All India Institute of Medical Sciences
name: Surendra K Sharma, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: