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Tuberculosis, PulmonaryPhase 4NCT03028129

Prevention of Tuberculosis in Prisons

A Phase 4 study testing Isoniazid 900 milligrams in people with Tuberculosis, Pulmonary and Antibiotic Prophylaxis, run by Federal University of Mato Grosso at 1 site in Brazil.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years, men onlyHealthy volunteers can take part
What is being tested?
Isoniazid 900 milligrams
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
467 participants
Where
1 siteBrazil
Study dates
4 Sep 2017to 10 Aug 2019
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • 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;

Trial locations and contacts

1 site in 1 country.

Brazil1 site
  • Roberto Oliveira

    Dourados, Mato Grosso do Sul, 78824210

Other trials in Brazil

About this study

Official title: Primary Prophylaxis for Prevention of TB in Prison's Populations

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.

Read the 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.

Being tested
Isoniazid 900 milligrams, Placebo
Keywords
Tuberculosis, Primary prevention, Prisoners, Controlled Clinical Trial, Isoniazid
Medical subject headings
Tuberculosis, Pulmonary, Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Isoniazid 900 milligramsDrug

    Also called Antibiotic Treatment

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

  • PlaceboDrug

    Also called Placebo Treatment

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

Study groups in NCT03028129
Study groupRoleWhat they receive
TreatmentExperimentalEach subject received two oral supervised weekly doses of isoniazid 900 milligrams.
Receives: Drug: Isoniazid 900 milligrams
ControlPlacebo comparatorEach subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2017 (estimated)
  2. Study start4 Sep 2017
  3. Primary completion10 Aug 2019
  4. Study completion10 Aug 2019

Why it stopped: Interim analysis showed efficacy less than 2.5%.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
467 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03028129
Sponsor's protocol ID
U1111-1189-0829
Status last verified
Oct 2019
First submitted
5 Dec 2016
Last updated
25 Oct 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994 Jan 14;263(5144):227-30. doi: 10.1126/science.8284673.

    PubMed 8284673
  • Barry CE 3rd, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ, Young D. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol. 2009 Dec;7(12):845-55. doi: 10.1038/nrmicro2236. Epub 2009 Oct 26.

    PubMed 19855401
  • Basu S, Stuckler D, McKee M. Addressing institutional amplifiers in the dynamics and control of tuberculosis epidemics. Am J Trop Med Hyg. 2011 Jan;84(1):30-7. doi: 10.4269/ajtmh.2011.10-0472.

    PubMed 21212197
  • Baussano I, Williams BG, Nunn P, Beggiato M, Fedeli U, Scano F. Tuberculosis incidence in prisons: a systematic review. PLoS Med. 2010 Dec 21;7(12):e1000381. doi: 10.1371/journal.pmed.1000381.

    PubMed 21203587
  • BERNSTEIN J, LOTT WA, STEINBERG BA, YALE HL. Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (nydrazid) and related compounds. Am Rev Tuberc. 1952 Apr;65(4):357-64. doi: 10.1164/art.1952.65.4.357. No abstract available.

    PubMed 14903503
  • Brites D, Gagneux S. Old and new selective pressures on Mycobacterium tuberculosis. Infect Genet Evol. 2012 Jun;12(4):678-85. doi: 10.1016/j.meegid.2011.08.010. Epub 2011 Aug 17.

    PubMed 21867778
  • Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C, Eiglmeier K, Garnier T, Gutierrez C, Hewinson G, Kremer K, Parsons LM, Pym AS, Samper S, van Soolingen D, Cole ST. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3684-9. doi: 10.1073/pnas.052548299. Epub 2002 Mar 12.

    PubMed 11891304
  • Carbone Ada S, Paiao DS, Sgarbi RV, Lemos EF, Cazanti RF, Ota MM, Junior AL, Bampi JV, Elias VP, Simionatto S, Motta-Castro AR, Pompilio MA, de Oliveira SM, Ko AI, Andrews JR, Croda J. Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study. BMC Infect Dis. 2015 Jan 22;15:24. doi: 10.1186/s12879-015-0764-8.

    PubMed 25608746
  • Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, Parkhill J, Malla B, Berg S, Thwaites G, Yeboah-Manu D, Bothamley G, Mei J, Wei L, Bentley S, Harris SR, Niemann S, Diel R, Aseffa A, Gao Q, Young D, Gagneux S. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet. 2013 Oct;45(10):1176-82. doi: 10.1038/ng.2744. Epub 2013 Sep 1.

    PubMed 23995134
  • Dowdy DW, Golub JE, Chaisson RE, Saraceni V. Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9557-62. doi: 10.1073/pnas.1203517109. Epub 2012 May 29.

    PubMed 22645356
  • Estevan AO, Oliveira SM, Croda J. Active and latent tuberculosis in prisoners in the Central-West Region of Brazil. Rev Soc Bras Med Trop. 2013 Jul-Aug;46(4):515-8. doi: 10.1590/0037-8682-1441-2013.

    PubMed 23904084
  • Ferreira MM, Ferrazoli L, Palaci M, Salles PS, Medeiros LA, Novoa P, Kiefer CR, Schechtmann M, Kritski AL, Johnson WD, Riley LW, Ferreira Junior OC. Tuberculosis and HIV infection among female inmates in Sao Paulo, Brazil: a prospective cohort study. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Oct 1;13(2):177-83. doi: 10.1097/00042560-199610010-00009.

    PubMed 8862283
  • Fournet N, Sanchez A, Massari V, Penna L, Natal S, Biondi E, Larouze B. Development and evaluation of tuberculosis screening scores in Brazilian prisons. Public Health. 2006 Oct;120(10):976-83. doi: 10.1016/j.puhe.2006.06.004. Epub 2006 Sep 11.

    PubMed 16965796
  • FOX HH. The chemical approach to the control of tuberculosis. Science. 1952 Aug 8;116(3006):129-34. doi: 10.1126/science.116.3006.129. No abstract available.

    PubMed 14950210
  • Hanson ML, Comstock GW, Haley CE. Community isoniazid prophylaxis program in an underdeveloped area of Alaska. Public Health Rep (1896). 1967 Dec;82(12):1045-56. No abstract available.

    PubMed 4966218

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Isoniazid 900 milligrams in people with Tuberculosis, Pulmonary and Antibiotic Prophylaxis, run by Federal University of Mato Grosso at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit. (time frame: up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03028129, which also lists 43 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2019.

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