TuberculosisPhase 4ADEPTTNCT03302299
Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT)
A Phase 4 study testing Isoniazid 300 Mg ORAL TABLET and Pyridoxine 25 Mg Oral Tablet in people with Tuberculosis and HIV/AIDS, run by University of California, San Francisco at 1 site in Uganda.
Trial summary
The Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) will examine the safety and tolerability of, and adherence to, 6 months of daily INH (6H) in 300 TB and HIV-infected persons (200 drinkers and 100 non-drinkers) in Uganda. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, HIV/AIDS, Alcohol Abuse
- What is being tested?
- Isoniazid 300 Mg ORAL TABLET and Pyridoxine 25 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 1 siteUganda
- Study dates
- 7 Apr 2017to 1 Apr 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years old
- Patient of the MRRH ISS Clinic
- HIV-infected
- Consume alcohol (self-reported consumption in the prior 3 months) (2/3) OR prior year non-drinker (1/3)
- Live within 2 hours of travel time to the ISS Clinic
- Fluent in either Runyankole or English
Show all 11Show fewer
- No ALT/AST elevations (< = 2X ULN) confirmed by testing
- On ART for at least 6 months
- No history of active TB, TB treatment, or TB preventive therapy
- No probable current active TB as determined by symptom screening and followed by chest X-ray and Xpert MTB/RIF (if symptomatic)
- Positive TST results confirmed by testing
Who cannot join
- Plans to move out of the catchment area within 6 months
- Probable TB via symptom screen and subsequent assessments
- History or current or past active TB, TB treatment, or TB preventive therapy
- ALT or AST >2x ULN
- Pregnant women
Trial locations and contacts
1 site in 1 country.
Uganda1 site
Mbarara University of Science and Technology/Mbarara Regional Referral Hospital
Mbarara
About this study
Official title: URBAN ARCH (3/5) Uganda Cohort TB Preventive Therapy for HIV-infected Alcohol Users in Uganda: an Evaluation of Safety Tolerability and Adherence
The Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) will examine the safety and tolerability of, and adherence to, 6 months of daily INH (6H) in 300 TB and HIV-infected persons (200 drinkers and 100 non-drinkers) in Uganda. The first aim is to evaluate the safety and tolerability of 6H overall and by level of alcohol use. The second aim is to estimate adherence and compare adherence by level of alcohol use and at 3 and 6 months. Self-reported measures of alcohol use will be augmented by phosphatidylethanol (PEth), an established biomarker of alcohol use. Objective measures of adherence will include electronic pill bottle monitoring and a novel measure of INH exposure, INH concentration in hair. The study will actively monitor for hepatotoxicity using the U.S. standard of care for TB preventive therapy for heavy drinkers and discontinue if any Grade 3/4 toxicities are detected. The investigators will use the safety, tolerability, and adherence results, together with the known efficacy and mortality benefit of TB preventive therapy in HIV-infected persons in SSA, and an established decision analytic model of TB preventive therapy to conduct the third aim: to determine whether the benefits of TB preventive therapy outweigh the toxicity risks for HIV-infected drinkers in resource limited settings. The study will additionally follow the cohort every 6 months after completing INH to monitor drinking and the development of active TB.
Read the detailed description
Tuberculosis (TB) is the leading cause of mortality in persons with HIV worldwide, accounting for 20-33% of HIV-related deaths, and is a high-priority area of research in HIV/AIDS by the NIH. TB preventive therapy decreases both all-cause mortality and active TB in persons with HIV by 30-50% above and beyond the benefits of antiretroviral therapy (ART) alone. Based on these findings, the World Health Organization (WHO) recommends isoniazid (INH) preventive therapy (IPT) for all persons with HIV in resource constrained settings. However, the WHO warns against the use of IPT in persons with "regular and heavy alcohol use." This exclusion stems from concern for increased hepatotoxicity in heavy drinkers in settings where liver enzymes are not routinely monitored. Heavy drinking in persons with HIV is very common, approximately 25%, in sub-Saharan Africa (SSA). Heavy drinking increases the risk for active TB at least threefold; thus, HIV-infected alcohol users should be prioritized for TB prevention. However, no studies have systematically assessed the safety of TB preventive therapy in heavy drinkers with or without HIV infection. It is critical to examine the safety and tolerability of TB preventive therapy for HIV-infected drinkers, given the high rates of HIV, TB infection, and alcohol comorbidities worldwide. While the risk of toxicity exists, the risk of TB disease could outweigh the toxicity harms. Thus, it is also crucial to determine whether the mortality benefits outweigh the toxicity risks for this significant portion of the HIV-infected population.
In addition, TB preventive therapy is only effective if taken consistently for the full course. Alcohol use is an established risk factor for decreased ART pill taking and active TB treatment discontinuation. Whether HIV-infected drinkers on ART can be adherent to TB preventive therapy is not known. Therefore it is essential to determine the level of adherence to TB preventive therapy by HIV-infected drinkers on ART, thus this study aims to examine adherence to TB preventative therapy as well.
This is a study to examine 6 months of daily INH (6H) among N=300 persons co-infected with HIV and TB. The aims of the study are:
Aim 1: To examine the safety and tolerability of 6H in HIV/TB co-infected drinkers, measured by hepatotoxicity and treatment discontinuation rates. The main aim is to estimate safety and tolerability overall among drinkers (primary) and by level of drinking (secondary).
Aim 2: To determine the level of TB preventive therapy adherence overall among drinkers and by level of drinking, and at 3 and 6 months. The main goal of this aim is to estimate adherence overall among drinkers (primary). Secondarily the investigators will estimate adherence by level of drinking (heavy, current but not heavy drinkers, and non-drinkers) and compare adherence across drinking levels. The investigators hypothesize that adherence will be highest among the non-drinkers.
Aim 3: To determine whether the benefits of providing TB preventive therapy to HIV-infected drinkers in resource-limited settings outweigh the risks compared to no treatment. The investigators hypothesize that providing TB preventive therapy will result in longer life expectancy and quality-adjusted life expectancy than not providing TB preventive therapy (current standard of care).
- Conditions
- Tuberculosis, HIV/AIDS, Alcohol Abuse
- Being tested
- Isoniazid 300 Mg ORAL TABLET, Pyridoxine 25 Mg Oral Tablet
- Keywords
- Adherence, Hepatotoxicity, Phosphatidtylethanol
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid 300 Mg ORAL TABLETDrug
Also called INH
The study intervention will include a single arm given (1) 6H: 300 mg INH daily by mouth for 6 months.
Pyridoxine 25 Mg Oral TabletDrug
Also called Vitamin B6
All participants will also receive 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months for the treatment duration to reduce the risk of INH-induced peripheral neuropathy.
| Study group | Role | What they receive |
|---|---|---|
| Isoniazid & pyridoxine | Experimental | Isoniazid 300 mg oral tablet: 300 mg daily by mouth for 6 months. Pyridoxine 25 mg oral tablet: 25mg daily by mouth for 6 months. Receives: Drug: Isoniazid 300 Mg ORAL TABLET; Drug: Pyridoxine 25 Mg Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity
Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period.
Measured: Hepatotoxicity occurring during the six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.
Secondary outcomes (4)
Number of Participants Who Discontinued Treatment
Lack of tolerability will be defined as any isoniazid (INH) treatment discontinuation prior to completion of the prescribed course (6 months of INH taken over a maximum period of 9 months) due to side effects or alanine transaminase (ALT)/aspartate transaminase (AST) elevations.
Measured: Six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.
Percentage of Participants With Suboptimal INH Medication Adherence
Suboptimal INH adherence was defined as <90% of days with at least 1 electronic medication management (EMM) pill cap opening in the previous 90 days, at 3- and 6-months.
Measured: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter)
Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days
Participants were asked "In the past 30 days, how many days in total have you not taken your pill?" and were presented with a visual analog scale (VAS) to indicate the percentage of INH taken in the past 30 days. We converted the VAS percentage into number of days out of 30 to match the first question. Our final self-report measure was the minimum number of the 2 self-reported measurements.
Measured: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INH
Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
The Self Rating Single Item (SRSI) adherence scale asks participants to rate their ability to take their medications as prescribed over the past 30 days. Participants reporting INH use in the prior 30 days at the 3- or 6-month interview are included here, and reported their INH adherence in the prior 30 days as excellent, very good, good, fair, poor, or very poor.
Measured: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INH
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2017
- Study start7 Apr 2017
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (117)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University, Boston Medical Center, Mbarara University of Science and Technology
- Responsible party
- Sponsor
- Investigators
- Judith A Hahn, PhD, MA, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03302299
- Sponsor's protocol ID
- 2U01AA020776-06
- Acronym
- ADEPTT
- Status last verified
- Sep 2023
- First submitted
- 15 Sep 2017
- Last updated
- 19 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators will make de-identified data available to investigators with relevant and well-articulated research plans, after the main study analyses have been conducted. No personal identifiers will be shared, and nor identifiers that could be linked back to the original study ID. In addition, some journals require de-identified data to be posted for public access.
Publications
Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD000171. doi: 10.1002/14651858.CD000171.pub3.
PubMed 20091503Edessa D, Likisa J. A Description of Mortality Associated with IPT plus ART Compared to ART Alone among HIV-Infected Individuals in Addis Ababa, Ethiopia: A Cohort Study. PLoS One. 2015 Sep 8;10(9):e0137492. doi: 10.1371/journal.pone.0137492. eCollection 2015.
PubMed 26348618TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
PubMed 26193126Ayele HT, Mourik MS, Debray TP, Bonten MJ. Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials. PLoS One. 2015 Nov 9;10(11):e0142290. doi: 10.1371/journal.pone.0142290. eCollection 2015.
PubMed 26551023Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, Gray GE, McIntyre JA, Chaisson RE, Martinson NA. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009 Mar 13;23(5):631-6. doi: 10.1097/QAD.0b013e328327964f.
PubMed 19525621Akolo C, Bada F, Okpokoro E, Nwanne O, Iziduh S, Usoroh E, Ali T, Ibeziako V, Oladimeji O, Odo M. Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons. World J Virol. 2015 May 12;4(2):105-12. doi: 10.5501/wjv.v4.i2.105.
PubMed 25964875Rangaka MX, Cavalcante SC, Marais BJ, Thim S, Martinson NA, Swaminathan S, Chaisson RE. Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection. Lancet. 2015 Dec 5;386(10010):2344-53. doi: 10.1016/S0140-6736(15)00323-2. Epub 2015 Oct 26.
PubMed 26515679Kader R, Govender R, Seedat S, Koch JR, Parry C. Understanding the Impact of Hazardous and Harmful Use of Alcohol and/or Other Drugs on ARV Adherence and Disease Progression. PLoS One. 2015 May 1;10(5):e0125088. doi: 10.1371/journal.pone.0125088. eCollection 2015.
PubMed 25933422Wandera B, Tumwesigye NM, Nankabirwa JI, Kambugu AD, Parkes-Ratanshi R, Mafigiri DK, Kapiga S, Sethi AK. Alcohol Consumption among HIV-Infected Persons in a Large Urban HIV Clinic in Kampala Uganda: A Constellation of Harmful Behaviors. PLoS One. 2015 May 11;10(5):e0126236. doi: 10.1371/journal.pone.0126236. eCollection 2015.
PubMed 25962171Kader R, Seedat S, Govender R, Koch JR, Parry CD. Hazardous and harmful use of alcohol and/or other drugs and health status among South African patients attending HIV clinics. AIDS Behav. 2014 Mar;18(3):525-34. doi: 10.1007/s10461-013-0587-9.
PubMed 23921585Kekwaletswe CT, Morojele NK. Alcohol use, antiretroviral therapy adherence, and preferences regarding an alcohol-focused adherence intervention in patients with human immunodeficiency virus. Patient Prefer Adherence. 2014 Mar 31;8:401-13. doi: 10.2147/PPA.S55547. eCollection 2014.
PubMed 24729688Medley A, Seth P, Pathak S, Howard AA, DeLuca N, Matiko E, Mwinyi A, Katuta F, Sheriff M, Makyao N, Wanjiku L, Ngare C, Bachanas P. Alcohol use and its association with HIV risk behaviors among a cohort of patients attending HIV clinical care in Tanzania, Kenya, and Namibia. AIDS Care. 2014;26(10):1288-97. doi: 10.1080/09540121.2014.911809. Epub 2014 Apr 29.
PubMed 24773163Soboka M, Tesfaye M, Feyissa GT, Hanlon C. Alcohol use disorders and associated factors among people living with HIV who are attending services in south west Ethiopia. BMC Res Notes. 2014 Nov 24;7:828. doi: 10.1186/1756-0500-7-828.
PubMed 25417542Narasimhan P, Wood J, Macintyre CR, Mathai D. Risk factors for tuberculosis. Pulm Med. 2013;2013:828939. doi: 10.1155/2013/828939. Epub 2013 Feb 12.
PubMed 23476764Lonnroth K, Williams BG, Stadlin S, Jaramillo E, Dye C. Alcohol use as a risk factor for tuberculosis - a systematic review. BMC Public Health. 2008 Aug 14;8:289. doi: 10.1186/1471-2458-8-289.
PubMed 18702821
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- URBAN ARCH (3/5) Uganda Cohort TB Preventive Therapy for HIV-infected Alcohol Users in Uganda: an Evaluation of Safety Tolerability and Adherence
- ClinicalTrials.gov ID
- NCT03302299
- Acronym / sponsor ID
- ADEPTT / 2U01AA020776-06
- Conditions
- Tuberculosis, HIV/AIDS, Alcohol Abuse
- Keywords
- Adherence, Hepatotoxicity, Phosphatidtylethanol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Boston University, Boston Medical Center, Mbarara University of Science and Technology
- Study start
- 7 Apr 2017 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 5 Oct 2017 (actual)
- Results
- Posted 19 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) will examine the safety and tolerability of, and adherence to, 6 months of daily INH (6H) in 300 TB and HIV-infected persons (200 drinkers and 100 non-drinkers) in Uganda. The first aim is to evaluate the safety and tolerability of 6H overall and by level of alcohol use. The second aim is to estimate adherence and compare adherence by level of alcohol use and at 3 and 6 months. Self-reported measures of alcohol use will be augmented by phosphatidylethanol (PEth), an established biomarker of alcohol use. Objective measures of adherence will include electronic pill bottle monitoring and a novel measure of INH exposure, INH concentration in hair. The study will actively monitor for hepatotoxicity using the U.S. standard of care for TB preventive therapy for heavy drinkers and discontinue if any Grade 3/4 toxicities are detected. The investigators will use the safety, tolerability, and adherence results, together with the known efficacy and mortality benefit of TB preventive therapy in HIV-infected persons in SSA, and an established decision analytic model of TB preventive therapy to conduct the third aim: to determine whether the benefits of TB preventive therapy outweigh the toxicity risks for HIV-infected drinkers in resource limited settings. The study will additionally follow the cohort every 6 months after completing INH to monitor drinking and the development of active TB.
Detailed description
Tuberculosis (TB) is the leading cause of mortality in persons with HIV worldwide, accounting for 20-33% of HIV-related deaths, and is a high-priority area of research in HIV/AIDS by the NIH. TB preventive therapy decreases both all-cause mortality and active TB in persons with HIV by 30-50% above and beyond the benefits of antiretroviral therapy (ART) alone. Based on these findings, the World Health Organization (WHO) recommends isoniazid (INH) preventive therapy (IPT) for all persons with HIV in resource constrained settings. However, the WHO warns against the use of IPT in persons with "regular and heavy alcohol use." This exclusion stems from concern for increased hepatotoxicity in heavy drinkers in settings where liver enzymes are not routinely monitored. Heavy drinking in persons with HIV is very common, approximately 25%, in sub-Saharan Africa (SSA). Heavy drinking increases the risk for active TB at least threefold; thus, HIV-infected alcohol users should be prioritized for TB prevention. However, no studies have systematically assessed the safety of TB preventive therapy in heavy drinkers with or without HIV infection. It is critical to examine the safety and tolerability of TB preventive therapy for HIV-infected drinkers, given the high rates of HIV, TB infection, and alcohol comorbidities worldwide. While the risk of toxicity exists, the risk of TB disease could outweigh the toxicity harms. Thus, it is also crucial to determine whether the mortality benefits outweigh the toxicity risks for this significant portion of the HIV-infected population.
In addition, TB preventive therapy is only effective if taken consistently for the full course. Alcohol use is an established risk factor for decreased ART pill taking and active TB treatment discontinuation. Whether HIV-infected drinkers on ART can be adherent to TB preventive therapy is not known. Therefore it is essential to determine the level of adherence to TB preventive therapy by HIV-infected drinkers on ART, thus this study aims to examine adherence to TB preventative therapy as well.
This is a study to examine 6 months of daily INH (6H) among N=300 persons co-infected with HIV and TB. The aims of the study are:
Aim 1: To examine the safety and tolerability of 6H in HIV/TB co-infected drinkers, measured by hepatotoxicity and treatment discontinuation rates. The main aim is to estimate safety and tolerability overall among drinkers (primary) and by level of drinking (secondary).
Aim 2: To determine the level of TB preventive therapy adherence overall among drinkers and by level of drinking, and at 3 and 6 months. The main goal of this aim is to estimate adherence overall among drinkers (primary). Secondarily the investigators will estimate adherence by level of drinking (heavy, current but not heavy drinkers, and non-drinkers) and compare adherence across drinking levels. The investigators hypothesize that adherence will be highest among the non-drinkers.
Aim 3: To determine whether the benefits of providing TB preventive therapy to HIV-infected drinkers in resource-limited settings outweigh the risks compared to no treatment. The investigators hypothesize that providing TB preventive therapy will result in longer life expectancy and quality-adjusted life expectancy than not providing TB preventive therapy (current standard of care).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Isoniazid & pyridoxine | Experimental | Drug: Isoniazid 300 Mg ORAL TABLET, Drug: Pyridoxine 25 Mg Oral TabletIsoniazid 300 mg oral tablet: 300 mg daily by mouth for 6 months. Pyridoxine 25 mg oral tablet: 25mg daily by mouth for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age > 18 years old
- Patient of the MRRH ISS Clinic
- HIV-infected
- Consume alcohol (self-reported consumption in the prior 3 months) (2/3) OR prior year non-drinker (1/3)
- Live within 2 hours of travel time to the ISS Clinic
Key exclusion criteria (5 listed)
- Plans to move out of the catchment area within 6 months
- Probable TB via symptom screen and subsequent assessments
- History or current or past active TB, TB treatment, or TB preventive therapy
- ALT or AST >2x ULN
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoniazid 300 Mg ORAL TABLETAlso: INHThe study intervention will include a single arm given (1) 6H: 300 mg INH daily by mouth for 6 months. | Drug | Isoniazid & pyridoxine |
| Pyridoxine 25 Mg Oral TabletAlso: Vitamin B6All participants will also receive 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months for the treatment duration to reduce the risk of INH-induced peripheral neuropathy. | Drug | Isoniazid & pyridoxine |
Primary outcome
Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity
Time frame: Hepatotoxicity occurring during the six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.
Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period.
4 secondary outcomes
Number of Participants Who Discontinued Treatment
Time frame: Six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.
Percentage of Participants With Suboptimal INH Medication Adherence
Time frame: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter)
Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days
Time frame: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INH
Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
Time frame: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INH
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20091503Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD000171. doi: 10.1002/14651858.CD000171.pub3.
- Background: PubMed 26348618Edessa D, Likisa J. A Description of Mortality Associated with IPT plus ART Compared to ART Alone among HIV-Infected Individuals in Addis Ababa, Ethiopia: A Cohort Study. PLoS One. 2015 Sep 8;10(9):e0137492. doi: 10.1371/journal.pone.0137492. eCollection 2015.
- Background: PubMed 26193126TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
- Background: PubMed 26551023Ayele HT, Mourik MS, Debray TP, Bonten MJ. Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials. PLoS One. 2015 Nov 9;10(11):e0142290. doi: 10.1371/journal.pone.0142290. eCollection 2015.
- Background: PubMed 19525621Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, Gray GE, McIntyre JA, Chaisson RE, Martinson NA. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009 Mar 13;23(5):631-6. doi: 10.1097/QAD.0b013e328327964f.
- Background: PubMed 25964875Akolo C, Bada F, Okpokoro E, Nwanne O, Iziduh S, Usoroh E, Ali T, Ibeziako V, Oladimeji O, Odo M. Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons. World J Virol. 2015 May 12;4(2):105-12. doi: 10.5501/wjv.v4.i2.105.
- Background: PubMed 26515679Rangaka MX, Cavalcante SC, Marais BJ, Thim S, Martinson NA, Swaminathan S, Chaisson RE. Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection. Lancet. 2015 Dec 5;386(10010):2344-53. doi: 10.1016/S0140-6736(15)00323-2. Epub 2015 Oct 26.
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- Background: PubMed 25962171Wandera B, Tumwesigye NM, Nankabirwa JI, Kambugu AD, Parkes-Ratanshi R, Mafigiri DK, Kapiga S, Sethi AK. Alcohol Consumption among HIV-Infected Persons in a Large Urban HIV Clinic in Kampala Uganda: A Constellation of Harmful Behaviors. PLoS One. 2015 May 11;10(5):e0126236. doi: 10.1371/journal.pone.0126236. eCollection 2015.
- Background: PubMed 23921585Kader R, Seedat S, Govender R, Koch JR, Parry CD. Hazardous and harmful use of alcohol and/or other drugs and health status among South African patients attending HIV clinics. AIDS Behav. 2014 Mar;18(3):525-34. doi: 10.1007/s10461-013-0587-9.
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- How AIDS Changed Everything: 2014 Global Statistics. UNAIDS;2015.Link provided by the sponsor.
- Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings.Link provided by the sponsor.
- UNAIDS Country Report, Uganda. 2014Link provided by the sponsor.
- Global Status Report on Alcohol and Health. Geneva: World Health Organization;2014Link provided by the sponsor.
- Individual participant dataSharing planned: No. The investigators will make de-identified data available to investigators with relevant and well-articulated research plans, after the main study analyses have been conducted. No personal identifiers will be shared, and nor identifiers that could be linked back to the original study ID. In addition, some journals require de-identified data to be posted for public access.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith A Hahn, PhD, MA principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Isoniazid 300 Mg ORAL TABLET and Pyridoxine 25 Mg Oral Tablet in people with Tuberculosis and HIV/AIDS, run by University of California, San Francisco at 1 site in Uganda.
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 11 inclusion and 5 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: finished, as of the sponsor's last update on 19 Oct 2023. 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 Uganda. 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. 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 19 Oct 2023). 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?
Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity (time frame: Hepatotoxicity occurring during the six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 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 NCT03302299, which also lists 117 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 19 Oct 2023.