Clinical trial NCT00164281: Study of Limited Versus Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana
Official title: A Randomized, Placebo-Controlled Study of Limited vs. Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Tuberculosis
HIV Infections
Keywords: TB
Tuberculosis
INH
Isoniazid
Preventive therapy
HIV
AIDS
Botswana
LTBI
Latent TB Infection
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Botswana Ministry of Health
name: United States Agency for International Development (USAID)
First posted: 2005-09-14
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: Randomized, double blinded, two-arm comparative trial of continuous vs. limited isoniazid 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.

Eligibility criteria: Inclusion Criteria:

1. HIV-infected
2. Age \>=18 years
3. Tuberculin skin test positive or negative
4. 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
5. Karnofsky performance status \>=60
6. Signed informed consent

Exclusion Criteria:

1. History of TB in the last 3 years or current active TB
2. History of noncompliance to chronic therapies

Primary outcomes:
measure: Incident tuberculosis
timeFrame: During enrolment
Secondary outcomes:
measure: Death
timeFrame: During enrolment
measure: Adverse events
timeFrame: During provision of study medication
Other outcomes:
Locations:
city: Gaborone and Francistown
country: Botswana
facility: Gaborone and Francistown Health Clinics
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Taraz Samandari, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.