Back to results

Prevention of Tuberculosis in Prisons

Primary Purpose

Tuberculosis, Pulmonary, Antibiotic Prophylaxis

Status

Terminated

Phase

Phase 4

Locations

Brazil

Study Type

Interventional

Intervention

Isoniazid 900 milligrams

Placebo

About this trial

This is an interventional prevention trial for Tuberculosis, Pulmonary focused on measuring Tuberculosis, Primary prevention, Prisoners, Controlled Clinical Trial, Isoniazid

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion criteria:

Age above 18 and under 45 at the time of inclusion;
Sign the informed consent form.

Exclusion criteria:

Be indigenous;
Active TB or previous use of isoniazid;
Score Alcohol Use Disorders Identification Test ≥15.
Reactive serology for HIV, hepatitis B and C;
Reactive result for quantiferon, considering as positive the result of Tube 1 and / or Tube22 above 0.2 IU / mL;
Liver enzymes (Aspartate aminotransferase and Alanate aminotransferase) three times the upper limit;
History or treatment for epilepsy;

Sites / Locations

Roberto Oliveira

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment

Control

Arm Description

Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.

Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).

Outcomes

Primary Outcome Measures

Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.

Number of participants who had a Quantiferon TB Gold Plus (QIAGEN®) score greater than or equal to 0.35 international units per milliliter, at the time of the premature exclusion visit, on all participants in the group.

Secondary Outcome Measures

Full Information

NCT ID

NCT03028129

First Posted

December 5, 2016

Last Updated

October 2, 2019

Sponsor

Federal University of Mato Grosso

Collaborators

Oswaldo Cruz Foundation

1. Study Identification

Unique Protocol Identification Number

NCT03028129

Brief Title

Prevention of Tuberculosis in Prisons

Official Title

Primary Prophylaxis for Prevention of TB in Prison's Populations

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Terminated

Why Stopped

Interim analysis showed efficacy less than 2.5%.

Study Start Date

September 4, 2017 (Actual)

Primary Completion Date

August 10, 2019 (Actual)

Study Completion Date

August 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Federal University of Mato Grosso

Collaborators

Oswaldo Cruz Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to determine if the isoniazid is effective in the prevention of tuberculosis in a prison population, exposed to the high endemicity of the disease.

Detailed Description

Despite being a known disease of mankind over 9000 years, tuberculosis (TB) is still a major public health problem in developing countries, mainly due to so-called highly endemic sites, such as prisons. It is Infectious disease, with airborne transmission, TB can present both the active or latent form. Despite the biological aspect of transmission, unhealthy environmental conditions (room without direct sunlight, poor ventilation and overcrowded) and individual factors (malnutrition, immunosuppression, use of alcohol and other drugs) have significant influence on transferability and infectivity. With the discovery of drugs active against Mycobacterium tuberculosis, it was observed a reduction of disease incidence in the world. Despite this declining incidence, World Health Organization (WHO) classifies TB as a public health problem due to the emergence of multidrug strains or extensively resistant to treatment, added to the cases of latent TB reactivation, observed with the advent of HIV/AIDS. Studies show a direct relationship between the incidence of TB and the prison environment. Nevertheless, the presence of prisons in one location increases the incidence of this disease, indicating that there is an exchange of disease between the prison and the community. Currently, control of TB in the prison system is based on the tracking of individuals with active TB and / or latent and, in their respective treatment. For the identification of individuals with active disease, it is necessary the recognition of respiratory symptoms (cough mainly) and sputum smear microscopy and sputum culture, and chest X-ray. As the search of individuals with latent form, must be carried to the skin test with Purified Protein Derived (PPD). Most of the units of the Brazilian's prison system these diagnostic methods are not available and hence the transport of individuals for their realization is necessary, generating an additional cost, in most cases, unfeasible process execution. With the completion of this study, it seek to determine the effectiveness of primary prophylaxis in the prison population in order to gather new scientific evidence, to bring affordable methods for the control of TB in prisons. Despite advances in diagnosis and treatment TB, this is the third leading cause of death from infectious diseases worldwide (Naghavi et al, 2015). In 2015, the WHO estimated incidence of 9.6 million new cases of TB in the world, with about 1.1 million deaths. For Brazil it was estimated incidence of 44 cases per 100,000 (WHO, 2015). The incidence of TB has declined about 2% per year, but this rate is not homogeneous in the global context. Brazil occupies the 22nd place in the ranking of the WHO with an estimated annual rate of 83,310 cases of the disease (Zumla et al, 2015). In the past seven years, it is estimated that the incidence declined only 0.7% (per year). A key factor in this slow progress in TB control in Brazil, and other emerging countries is the existence of high-risk subpopulations, including slums and prisons, which act as reservoirs and amplifiers for the transmission of the disease (Basu; Stückler; Mckee 2011; Dowdy et al, 2012). A recent systematic review showed that the average incidence of TB in the prison population can be up to 23 times that recorded in the general population (Baussano et al, 2010). With the fourth largest prison populations in the world, is observed in Brazil, the increased incidence of TB among prisoners in the last seven years. Although prisoners represent only 0.3% of the population, the increase in the prison population over this period resulted in almost doubling the proportion of all TB cases that occur among prisoners (4.1% in 2007, 8, 1% in 2013). The arrests are in an ideal environment for the spread of TB, since they show individuals users of tobacco and alcohol in high doses, in addition to drug abuse in overcrowded cells with poor ventilation and with limited access to care health and diagnosis of TB. Currently, the Ministry of Health recommends active search for TB at the entrance to the prison and once a year by chest X-ray. Due to the cost and logistics, most prisons do not adhere to this recommendation. There is also a clear recommendation not to use the tuberculin skin test or perform the treatment for latent tuberculosis. If the procedures for active case detection and / or prophylactic treatment would impact the high transmission in prisons is a question that still remains open (Al-Darraji; Kamarulzamn; Altice, 2012). The concentration of cases of TB in prisons can represent both an obstacle and an opportunity to control the disease, depending on the effectiveness of interventions in these environments. Preliminary studies show high annual rate of TB infection (26%) among the prison population of 12 penitentiaries of Mato Grosso do Sul. Besides the large burden of disease in this population is significant dispersion of the TB prison to the community (Sacchi et al, 2015). Cross-sectional studies show high yield annual screening for TB, however, the effectiveness of this measure combined with other interventions remains unclear (Ferreira et al, 1996; Fournet et al, 2006; Lemos et al, 2014; Vieira et al, 2010; Sanches et al, 2013; Walnut; Abrahão; Galesi, 2012; Kuhleis et al, 2012; Estevan; Oliveira; Croda, 2013). Due to the combination of high force of infection in prisons and short prison term, primary prophylaxis may be an effective intervention. This new approach has never been evaluated in the context of prisons in low and middle income countries; to assess the impact of program strategies for TB screening and prophylaxis, longitudinal data will be essential. Given the infrastructure that was created for long-term prospective studies in Brazil, there is an excellent opportunity to close the critical knowledge gaps that have been barriers to effective implementation of TB control in high transmission prisons.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis, Pulmonary, Antibiotic Prophylaxis

Keywords

Tuberculosis, Primary prevention, Prisoners, Controlled Clinical Trial, Isoniazid

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

467 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).

Intervention Type

Drug

Intervention Name(s)

Isoniazid 900 milligrams

Other Intervention Name(s)

Antibiotic Treatment

Intervention Description

Oral tablet, with the isoniazid 900mg, given two weekly. The administration will be supervised.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo Treatment

Intervention Description

Oral tablet, without the active ingredient, similar in size, weight, color, taste and odor.

Primary Outcome Measure Information:

Title

Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.

Description

Time Frame

up to 6 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Age above 18 and under 45 at the time of inclusion; Sign the informed consent form. Exclusion criteria: Be indigenous; Active TB or previous use of isoniazid; Score Alcohol Use Disorders Identification Test ≥15. Reactive serology for HIV, hepatitis B and C; Reactive result for quantiferon, considering as positive the result of Tube 1 and / or Tube22 above 0.2 IU / mL; Liver enzymes (Aspartate aminotransferase and Alanate aminotransferase) three times the upper limit; History or treatment for epilepsy;

Overall Study Officials: