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Prevention of Tuberculosis in Prisons

Sponsor
Federal University of Mato Grosso (Other)
Overall Status
Terminated
CT.gov ID
NCT03028129
Collaborator
Oswaldo Cruz Foundation (Other)
467
Enrollment
1
Location
2
Arms
23.2
Actual Duration (Months)
20.2
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Isoniazid 900 milligrams
  • Drug: Placebo
 Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
467 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Primary Prophylaxis for Prevention of TB in Prison's Populations
Actual Study Start Date :
Sep 4, 2017
Actual Primary Completion Date :
Aug 10, 2019
Actual Study Completion Date :
Aug 10, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment

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

Drug: Isoniazid 900 milligrams
Oral tablet, with the isoniazid 900mg, given two weekly. The administration will be supervised.
Other Names:
  • Antibiotic Treatment

    		•
    Placebo Comparator: Control

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

    Drug: Placebo
    Oral tablet, without the active ingredient, similar in size, weight, color, taste and odor.
    Other Names:
  • Placebo Treatment

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit. [up to 6 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Roberto Oliveira Dourados Mato Grosso Do Sul Brazil 78824210

    Sponsors and Collaborators

    • Federal University of Mato Grosso
    • Oswaldo Cruz Foundation

    Investigators

    • Study Chair: Flora MF Moreira, Graduate, MsC Student
    • Study Chair: Andrea SS Carbone, MsC, PhD student
    • Study Chair: Flavia PC Sacchi, MsC, PhD student
    • Study Chair: Paulo CP Santos, Graduate, MsC Student
    • Study Chair: Rafaele CP Araújo, MsC, PhD student
    • Study Chair: Alessandra C Leite, MsC, PhD student
    • Study Chair: Cassia B Reis, PhD, Pos doc Student
    • Study Chair: Valeria C Rolla, PhD, Professor
    • Study Chair: Jason R Andrews, PhD, Professor

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Roberto D Oliveira, PhD Student, Federal University of Mato Grosso
    ClinicalTrials.gov Identifier:
    NCT03028129
    Other Study ID Numbers:
    • U1111-1189-0829
    First Posted:
    Jan 23, 2017
    Last Update Posted:
    Oct 25, 2019
    Last Verified:
    Oct 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Roberto D Oliveira, PhD Student, Federal University of Mato Grosso
    Tuberculosis
    Primary prevention
    Prisoners
    Controlled Clinical Trial
    Isoniazid
    Additional relevant MeSH terms:
    Tuberculosis
    Tuberculosis, Pulmonary
    Anti-Bacterial Agents
    Isoniazid

    Study Results

    Participant Flow

    Recruitment Details Eligible participants were interviewed for eligibility criteria (age, race, alcohol use, comorbidities) and laboratory tests (HIV, hepatitis B and C, liver enzymes, interferon gamma dosing for tuberculosis antigens and active tuberculosis).
    Pre-assignment Detail Study was discontinued at ninth month after interim analysis and showed efficacy in intervention group less than 2.5%
    Arm/Group Title Treatment Control
    Arm/Group Description Each subject received two oral supervised weekly doses of isoniazid 900 milligrams. Each subject received two weekly supervised oral doses of placebo, without the active ingredient, similar in size, weight, color, taste and odor.
    Period Title: Overall Study
    STARTED 258 209
    COMPLETED 132 122
    NOT COMPLETED 126 87

    Baseline Characteristics

    Arm/Group Title Treatment Control Total
    Arm/Group 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). Total of all reporting groups
    Overall Participants 258 209 467
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    29.2
    (6.7)
    29.0
    (7.1)
    29.1
    (6.9)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    258
    100%
    209
    100%
    467
    100%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    0.4%
    1
    0.5%
    2
    0.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    22
    8.5%
    9
    4.3%
    31
    6.6%
    White
    130
    50.4%
    109
    52.2%
    239
    51.2%
    More than one race
    105
    40.7%
    90
    43.1%
    195
    41.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Brazil
    258
    100%
    209
    100%
    467
    100%

    Outcome Measures

    1. Primary Outcome
    Title Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.
    Description 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.
    Time Frame up to 6 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of isoniazid or placebo and who had blood sample collected to QFT examination at premature exclusion visit.
    Arm/Group Title Treatment Control
    Arm/Group 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).
    Measure Participants 132 122
    Number [participants]
    49
    19%
    77
    36.8%

    Adverse Events

    Time Frame 9 months
    Adverse Event Reporting Description On the intervention days, all participants were asked about the presence of any unusual signs and / or symptoms. Data were recorded in a log containing start and end date, event description, degree and intervention performed.
    Arm/Group Title Treatment Control
    Arm/Group 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).
    All Cause Mortality
    Treatment Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/258 (0%) 0/209 (0%)
    Serious Adverse Events
    Treatment Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/258 (0.4%) 1/209 (0.5%)
    Hepatobiliary disorders
    Elevated SGOT 1/258 (0.4%) 1 1/209 (0.5%) 1
    Other (Not Including Serious) Adverse Events
    Treatment Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 190/258 (73.6%) 109/209 (52.2%)
    Gastrointestinal disorders
    Gastric pain 27/258 (10.5%) 27 15/209 (7.2%) 15
    Nausea 20/258 (7.8%) 20 4/209 (1.9%) 4
    General disorders
    Malaise 29/258 (11.2%) 29 7/209 (3.3%) 7
    Infections and infestations
    Flu syndrome 7/258 (2.7%) 7 15/209 (7.2%) 15
    Nervous system disorders
    Dizziness 27/258 (10.5%) 27 8/209 (3.8%) 8
    Headache 30/258 (11.6%) 30 15/209 (7.2%) 15
    Psychiatric disorders
    Somnolence 20/258 (7.8%) 20 9/209 (4.3%) 9
    Respiratory, thoracic and mediastinal disorders
    Cough 21/258 (8.1%) 21 24/209 (11.5%) 24
    Chest pain 9/258 (3.5%) 9 12/209 (5.7%) 12

    Limitations/Caveats

    Loss to follow-up Interruption of the study Arms presented differential group allocation Statistical power to detect the primary endpoint was 73%, lower than estimated in our sample size calculation

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Julio Croda
    Organization Federal University of Mato Grosso do Sul
    Phone +5567981229959
    Email julio.croda@ufms.br
    Responsible Party:
    Roberto D Oliveira, PhD Student, Federal University of Mato Grosso
    ClinicalTrials.gov Identifier:
    NCT03028129
    Other Study ID Numbers:
    • U1111-1189-0829
    First Posted:
    Jan 23, 2017
    Last Update Posted:
    Oct 25, 2019
    Last Verified:
    Oct 1, 2019