NCT00164281

Brief Summary

This is a randomized, blinded, two-arm comparative trial of continued versus limited isoniazid (INH) tuberculosis (TB) preventive therapy in HIV-infected adults in Gaborone and Francistown, Botswana. Subjects will be accrued over two years and followed for a minimum of 36 months.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,000

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2004

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2004

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

September 9, 2005

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 14, 2005

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2011

Completed
Last Updated

February 6, 2014

Status Verified

February 1, 2014

Enrollment Period

4.7 years

First QC Date

September 9, 2005

Last Update Submit

February 5, 2014

Conditions

TuberculosisHIV Infections

Keywords

TBTuberculosisINHIsoniazidPreventive therapyHIVAIDSBotswanaLTBILatent TB Infection

Outcome Measures

Primary Outcomes (1)

  • Incident tuberculosis

    During enrolment

Secondary Outcomes (2)

  • Death

    During enrolment

  • Adverse events

    During provision of study medication

Study Arms (1)

Continuous vs limited isoniazid

EXPERIMENTAL

The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication). The treatment (experimental arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).

Drug: Isoniazid

Interventions

IsoniazidDRUG

Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months vs 36 months.

Also known as: Isonicotinic Acid Hydrazide
Continuous vs limited isoniazid

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HIV-infected
  • Age \>=18 years
  • Tuberculin skin test positive or negative
  • Laboratory:
  • Hemoglobin (Hgb) \>6.5 gm/dl;
  • Neutrophil count \>1,000 cells/mm3;
  • Platelets \>75,000/mm3;
  • AST (SGOT) \<122 U/L;
  • Creatinine \<1.5 mg/dl;
  • Beta HCG = negative
  • Karnofsky performance status \>=60
  • Signed informed consent

You may not qualify if:

  • History of TB in the last 3 years or current active TB
  • History of noncompliance to chronic therapies

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Gaborone and Francistown Health Clinics

Gaborone and Francistown, Botswana

Location

Related Publications (10)

  • Agizew T, Bachhuber MA, Nyirenda S, Makwaruzi VZ, Tedla Z, Tallaksen RJ, Parker JE, Mboya JJ, Samandari T. Association of chest radiographic abnormalities with tuberculosis disease in asymptomatic HIV-infected adults. Int J Tuberc Lung Dis. 2010 Mar;14(3):324-31.

    PMID: 20132624BACKGROUND

  • Agizew TB, Arwady MA, Yoon JC, Nyirenda S, Mosimaneotsile B, Tedla Z, Motsamai O, Kilmarx PH, Wells CD, Samandari T. Tuberculosis in asymptomatic HIV-infected adults with abnormal chest radiographs screened for tuberculosis prevention. Int J Tuberc Lung Dis. 2010 Jan;14(1):45-51.

    PMID: 20003694BACKGROUND

  • Mosimaneotsile B, Mathoma A, Chengeta B, Nyirenda S, Agizew TB, Tedla Z, Motsamai OI, Kilmarx PH, Wells CD, Samandari T. Isoniazid tuberculosis preventive therapy in HIV-infected adults accessing antiretroviral therapy: a Botswana Experience, 2004-2006. J Acquir Immune Defic Syndr. 2010 May 1;54(1):71-7. doi: 10.1097/QAI.0b013e3181c3cbf0.

    PMID: 19934764BACKGROUND

  • Tedla Z, Nyirenda S, Peeler C, Agizew T, Sibanda T, Motsamai O, Vernon A, Wells CD, Samandari T. Isoniazid-associated hepatitis and antiretroviral drugs during tuberculosis prophylaxis in hiv-infected adults in Botswana. Am J Respir Crit Care Med. 2010 Jul 15;182(2):278-85. doi: 10.1164/rccm.200911-1783OC. Epub 2010 Apr 8.

    PMID: 20378730BACKGROUND

  • Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Shang N, Mosimaneotsile B, Motsamai OI, Bozeman L, Davis MK, Talbot EA, Moeti TL, Moffat HJ, Kilmarx PH, Castro KG, Wells CD. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 May 7;377(9777):1588-98. doi: 10.1016/S0140-6736(11)60204-3. Epub 2011 Apr 12.

    PMID: 21492926RESULT

  • Gust DA, Mosimaneotsile B, Mathebula U, Chingapane B, Gaul Z, Pals SL, Samandari T. Risk factors for non-adherence and loss to follow-up in a three-year clinical trial in Botswana. PLoS One. 2011 Apr 25;6(4):e18435. doi: 10.1371/journal.pone.0018435.

    PMID: 21541021RESULT

  • Chaisson LH, Kass NE, Chengeta B, Mathebula U, Samandari T. Repeated assessments of informed consent comprehension among HIV-infected participants of a three-year clinical trial in Botswana. PLoS One. 2011;6(10):e22696. doi: 10.1371/journal.pone.0022696. Epub 2011 Oct 27.

    PMID: 22046230RESULT

  • Sibanda T, Tedla Z, Nyirenda S, Agizew T, Marape M, Miranda AG, Reuter H, Johnson JL, Samandari T. Anti-tuberculosis treatment outcomes in HIV-infected adults exposed to isoniazid preventive therapy in Botswana. Int J Tuberc Lung Dis. 2013 Feb;17(2):178-85. doi: 10.5588/ijtld.12.0314.

    PMID: 23317952RESULT

  • Taylor AW, Mosimaneotsile B, Mathebula U, Mathoma A, Moathlodi R, Theebetsile I, Samandari T. Pregnancy outcomes in HIV-infected women receiving long-term isoniazid prophylaxis for tuberculosis and antiretroviral therapy. Infect Dis Obstet Gynecol. 2013;2013:195637. doi: 10.1155/2013/195637. Epub 2013 Mar 7.

    PMID: 23533318RESULT

  • Tedla Z, Nguyen ML, Sibanda T, Nyirenda S, Agizew TB, Girde S, Rose CE, Samandari T. Isoniazid-associated hepatitis in adults infected with HIV receiving 36 months of isoniazid prophylaxis in Botswana. Chest. 2015 May;147(5):1376-1384. doi: 10.1378/chest.14-0215.

    PMID: 25340318DERIVED

Related Links

MeSH Terms

Conditions

TuberculosisHIV InfectionsAcquired Immunodeficiency Syndrome

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

HydrazinesOrganic ChemicalsIsonicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Taraz Samandari, MD, PHD

    Centers for Disease Control and Prevention

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2005

First Posted

September 14, 2005

Study Start

November 1, 2004

Primary Completion

July 1, 2009

Study Completion

May 1, 2011

Last Updated

February 6, 2014

Record last verified: 2014-02

Locations

BO(1)