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| Name | Class |
|---|---|
| Botswana Ministry of Health | OTHER_GOV |
| United States Agency for International Development (USAID) | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continuous isoniazid | Experimental | The treatment (experimental arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid). |
|
| Limited isoniazid (6 months) + placebo | Placebo Comparator | Participants receive 6 months of open-label isoniazid followed by 30 months of placebo (coded medication). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isoniazid | Drug | Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months vs 36 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Incident Tuberculosis | Incident tuberculosis during follow-up. Tuberculosis cases were categorized as: Definite: ≥1 positive culture for M. tuberculosis or ≥2 sputum smears positive for acid-fast bacilli; Probable: 1 sputum smear or biopsy specimen positive for acid-fast bacilli; Possible: clinical diagnosis with negative or unavailable smear/culture results. Outcome data include definite, probable, and possible tuberculosis cases combined, consistent with the published analysis. | During follow-up (36 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Died | All-cause mortality during the 36-month follow-up period. | During follow-up (36 months) |
| Tuberculosis and Death Composite Outcome | Composite of incident tuberculosis and all deaths during the 36-month follow-up period. The paper presents this as "Tuberculosis and all deaths." |
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Inclusion Criteria:
HIV-infected
Age >=18 years
Tuberculin skin test positive or negative
Laboratory:
Karnofsky performance status >=60
Signed informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Taraz Samandari, MD, PHD | Centers for Disease Control and Prevention | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gaborone and Francistown Health Clinics | Gaborone | Botswana |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20132624 | Background | 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. | |
| 20003694 | Background | 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. |
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The planned sample size was 2000 participants; however, 1995 participants were ultimately enrolled and randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Continuous Isoniazid Arm | The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months. |
| FG001 | Limited (Placebo) Isoniazid Arm | The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Continuous Isoniazid Arm | The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid) for an additional 30 months. Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Incident Tuberculosis | Incident tuberculosis during follow-up. Tuberculosis cases were categorized as: Definite: ≥1 positive culture for M. tuberculosis or ≥2 sputum smears positive for acid-fast bacilli; Probable: 1 sputum smear or biopsy specimen positive for acid-fast bacilli; Possible: clinical diagnosis with negative or unavailable smear/culture results. Outcome data include definite, probable, and possible tuberculosis cases combined, consistent with the published analysis. | Posted | Count of Participants | Participants | During follow-up (36 months) |
|
From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Continuous Isoniazid Arm | The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatitis | Hepatobiliary disorders | Systematic Assessment |
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Use of antiretroviral therapy was not controlled in the study design; therefore, assessment of antiretroviral therapy effects has limitations similar to observational cohort analyses. Findings may not be generalizable to populations that do not undergo similar screening procedures.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Taraz Samandari | US CDC | 4046391676 | tts0@cdc.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 1, 2008 | Nov 11, 2022 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 22, 2004 | Nov 11, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D015658 | HIV Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
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| ID | Term |
|---|---|
| D007538 | Isoniazid |
| ID | Term |
|---|---|
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
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|
| During follow-up (36 months) |
| 19934764 | Background | 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. |
| 20378730 | Background | 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. |
| 21492926 | Result | 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. |
| 21541021 | Result | 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. |
| 22046230 | Result | 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. |
| 23317952 | Result | 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. |
| 23533318 | Result | 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. |
| 25340318 | Derived | 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. |
| Limited (Placebo) Isoniazid Arm |
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| OG001 |
| Limited (Placebo) Isoniazid Arm |
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months. |
|
|
| Secondary | Number of Participants Who Died | All-cause mortality during the 36-month follow-up period. | All randomized participants were included in the mortality analysis (Continuous isoniazid arm: N=1006; placebo arm: N=989). | Posted | Count of Participants | Participants | During follow-up (36 months) |
|
|
|
| Secondary | Tuberculosis and Death Composite Outcome | Composite of incident tuberculosis and all deaths during the 36-month follow-up period. The paper presents this as "Tuberculosis and all deaths." | All randomized participants were included in the composite tuberculosis and death analysis. | Posted | Count of Participants | Participants | During follow-up (36 months) |
|
|
|
| 39 |
| 1,006 |
| 9 |
| 1,006 |
| 0 |
| 1,006 |
| EG001 | Limited (Placebo) Isoniazid Arm | The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication). Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months. | 38 | 989 | 6 | 989 | 0 | 989 |
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Peripheral Neuropathy | Nervous system disorders | Systematic Assessment |
|
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| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012897 | Slow Virus Diseases |
| D006571 |
| Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |