TuberculosisHAART-IPTNCT00463086
Isoniazid Plus Antiretroviral Therapy to Prevent Tuberculosis in HIV-infected Persons
A study testing isoniazid in people with Tuberculosis and Latent Tuberculosis Infection, run by University of Cape Town at 1 site in South Africa.
Trial summary
The purpose of this study is to evaluate whether isoniazid can safely (and further) reduce the risk of tuberculosis in HIV infected people receiving HAART. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Latent Tuberculosis Infection, HIV Infections
- What is being tested?
- isoniazid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,368 participants
- Where
- 1 siteSouth Africa
- Study dates
- Nov 2007to Nov 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Male and female attendees (age ≥18yo) of the Ubuntu HIV and ARV Clinic identified as eligible for the ARV programme will be invited to participate.
- Willingness to participate
- Able to engage in informed consent procedures
Who cannot join
- Evidence of active TB or suspicion of active TB as determined by a symptoms screening algorithm.
- Current TB chemotherapy ( TB treatment completed in the preceding 30 days will not be an exclusion)
- Current or previous treatment of latent TB infection since HIV infection (any duration)
- Current treatment with fluoroquinolones or other antibiotics with significant anti-tuberculous activity currently being used to treat TB in South Africa
- Past reaction/intolerance to INH.
- Acute hepatitis or existing Grade III-IV peripheral neuropathy.
- Pregnancy or < 6weeks post-partum period (Due to increased risk of hepatotoxicity).
- Grade III or higher baseline abnormal liver function. (Note: toxicity grades are all according to ACTG toxicity tables for persons on ART).
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Ubuntu Clinic,Site B Khayelitsha
Cape Town, Western Cape
About this study
Official title: A Randomized-controlled Trial of Isoniazid Plus Highly Active Antiretroviral Therapy Against Placebo to Prevent Tuberculosis in HIV-infected Persons
The purpose of this study is to evaluate whether isoniazid can safely (and further) reduce the risk of tuberculosis in HIV infected people receiving HAART.
Read the detailed description
The incidence of Tuberculosis (TB) in poor settlements around Cape Town continues to rise despite highly-active-anti-retroviral therapy (HAART) roll-out and DOTS. In Khayelitsha district, where this project will be conducted, TB incidence is about 1600/100000. There is an equally high HIV prevalence, currently 33%. Over 50% of adults presenting with active TB are co-infected with HIV and a third of all patients starting HAART have active TB. Although HAART has been shown to reduce the overall risk of TB by 59-80%, this risk still far exceeds the general risk. In the Khayelitsha HAART cohort, the risk of developing TB whilst on HAART is ~12 per 100 p-y. In the nearby community of Gugulethu, there is a 14% risk of active TB with at least half of the cases occurring within the first 3months on HAART. In a region where RD1-detected prevalence of latent TB infection is at least 80%, there is a real concern that TB will likely undo the benefit of HAART in the long run. Additional measures are therefore required to reduce the risk of TB in those already receiving or starting HAART. Isoniazid preventive therapy (IPT) represents an option but there is insufficient evidence to determine whether IPT can further (and safely) reduce the risk of TB in the HAART era. In a RCT, we propose to evaluate whether IPT can reduce the risk of active TB in patients receiving HAART.
A total minimum sample size of 1204 is required for the study to detect a 35% reduction in the hazard rates for tuberculosis in the intervention group (h1= 0.052) compared to the control group (h0=0.085) at a power of 80% and a Type II error of 0.05. Our maximum targeted sample size when losses to follow-up and subgroup analyses are considered is 1445. Development of TB will be the primary endpoint.
Additional information (on 10 August 2010):
Recruitment and enrolment into the study was completed in October 2009. We have screened over 2000 patients already on ART and those newly starting ART. However, instead of enrolling our desired maximum sample size of 1445, a revised minimum total of 1368 were instead randomized to the study drug. This followed an amendment to the sample size necessitated by new information on the clinical site; primarily higher rates of patients lost to follow-up at the clinical site than previously anticipated. The amendment to our sample size was reported to, and acknowledged by, the Research Ethics Committee of the University of Cape Town. Follow-up of participants will continue until Oct/November 2011.
- Conditions
- Tuberculosis, Latent Tuberculosis Infection, HIV Infections
- Being tested
- isoniazid, Placebo
- Keywords
- Tuberculosis, TB, Mycobacteria, HIV, Human immunodeficiency virus, Latent tuberculosis infection, HAART, Highly active anti-retroviral therapy, Isoniazid preventive therapy, INH, Opportunistic infections, HIV-1, Treatment Experienced, AIDS, Mycobacterium Tuberculosis
- Medical subject headings
- Tuberculosis, Latent Tuberculosis, HIV Infections, Mycobacterium Infections, Acquired Immunodeficiency Syndrome, Opportunistic Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isoniazidDrug
A self-administered daily dose of 5mg/kg of Isoniazid or placebo for 12months(300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)
PlaceboDrug
A self-administered dose of 5mg/kg of placebo (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)
| Study group | Role | What they receive |
|---|---|---|
| 1.Isoniazid (INH) | Experimental | A self-administered daily dose of 5mg/kg of Isoniazid (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) Receives: Drug: isoniazid |
| 2. Placebo | Placebo comparator | A self-administered daily dose of 5mg/kg of placebo for 12months (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of development of TB (microbiologically confirmed TB or highly probable TB) during the 36 month risk period
Measured: Patients are assessed for TB one two monthly at each ART re-fill appointment
Secondary outcomes (5)
Rate of drug toxicity (specifically, peripheral neuropathy, hepatitis +/-raised ALT grade III or worse and allergic rashes grade III or worse
Measured: during the intervention period (ALT determined at baseline, 1, 2 and 3 months and then 3-monthly. the last safety determination is at 12 months post initiation of the study drug)
Proportions adhering to study drug and HAART at the end of each study year as measured by pharmacy refills
Measured: 1 month to two monthly, depending on the individual patient's clinic appointment
Rate of development of INH monoresistance during the 36 month risk period.
Measured: 36 months
Death
Measured: 36 months
Worsening ART outcomes (virological and immunological failure)
Measured: CD4+count and viral load are assessed as per clinic protocol (6 monthly post ART initiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2007 (estimated)
- Study startNov 2007
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,368 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, Imperial College London, Johns Hopkins University, London School of Hygiene and Tropical Medicine
- Responsible party
- Principal investigator, Prof Gary Maartens, University of Cape Town
- Investigators
- Gary Maartens (overall PI), FCP, Principal investigator, University of Cape TownEric Goemaere (co-investigator), MBBS, Study director, Medecins Sans Frontieres, NetherlandsMolebogeng X Rangaka (Lead Investigator), MBChB, Study director, University of Cape TownGilles van Cutsem co-investigator), MBBS, Study director, Medecins Sans Frontieres, NetherlandsAndrew Boulle co-investigator), FCP, Study director, University of Cape TownRobert J Wilkinson (PI:Immunology Studies), FRCP, Study director, Wellcome TrustShahied Mathee (Ubuntu PMO), MBChB, Study director, Provincial Government of Western Cape
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00463086
- Sponsor's protocol ID
- HAARTIPT07
- Acronym
- HAART-IPT
- Status last verified
- Jul 2012
- First submitted
- 19 Apr 2007
- Last updated
- 17 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rangaka MX, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, van Cutsem G, Wilkinson KA, Goliath R, Mathee S, Goemaere E, Maartens G. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial. Lancet. 2014 Aug 23;384(9944):682-90. doi: 10.1016/S0140-6736(14)60162-8. Epub 2014 May 13.
PubMed 24835842
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized-controlled Trial of Isoniazid Plus Highly Active Antiretroviral Therapy Against Placebo to Prevent Tuberculosis in HIV-infected Persons
- ClinicalTrials.gov ID
- NCT00463086
- Acronym / sponsor ID
- HAART-IPT / HAARTIPT07
- Conditions
- Tuberculosis, Latent Tuberculosis Infection, HIV Infections
- Keywords
- Tuberculosis, TB, Mycobacteria, HIV, Human immunodeficiency virus, Latent tuberculosis infection, HAART, Highly active anti-retroviral therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,368 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, Imperial College London, Johns Hopkins University, London School of Hygiene and Tropical Medicine
- Study start
- Nov 2007
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 20 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether isoniazid can safely (and further) reduce the risk of tuberculosis in HIV infected people receiving HAART.
Detailed description
The incidence of Tuberculosis (TB) in poor settlements around Cape Town continues to rise despite highly-active-anti-retroviral therapy (HAART) roll-out and DOTS. In Khayelitsha district, where this project will be conducted, TB incidence is about 1600/100000. There is an equally high HIV prevalence, currently 33%. Over 50% of adults presenting with active TB are co-infected with HIV and a third of all patients starting HAART have active TB. Although HAART has been shown to reduce the overall risk of TB by 59-80%, this risk still far exceeds the general risk. In the Khayelitsha HAART cohort, the risk of developing TB whilst on HAART is ~12 per 100 p-y. In the nearby community of Gugulethu, there is a 14% risk of active TB with at least half of the cases occurring within the first 3months on HAART. In a region where RD1-detected prevalence of latent TB infection is at least 80%, there is a real concern that TB will likely undo the benefit of HAART in the long run. Additional measures are therefore required to reduce the risk of TB in those already receiving or starting HAART. Isoniazid preventive therapy (IPT) represents an option but there is insufficient evidence to determine whether IPT can further (and safely) reduce the risk of TB in the HAART era. In a RCT, we propose to evaluate whether IPT can reduce the risk of active TB in patients receiving HAART.
A total minimum sample size of 1204 is required for the study to detect a 35% reduction in the hazard rates for tuberculosis in the intervention group (h1= 0.052) compared to the control group (h0=0.085) at a power of 80% and a Type II error of 0.05. Our maximum targeted sample size when losses to follow-up and subgroup analyses are considered is 1445. Development of TB will be the primary endpoint.
Additional information (on 10 August 2010):
Recruitment and enrolment into the study was completed in October 2009. We have screened over 2000 patients already on ART and those newly starting ART. However, instead of enrolling our desired maximum sample size of 1445, a revised minimum total of 1368 were instead randomized to the study drug. This followed an amendment to the sample size necessitated by new information on the clinical site; primarily higher rates of patients lost to follow-up at the clinical site than previously anticipated. The amendment to our sample size was reported to, and acknowledged by, the Research Ethics Committee of the University of Cape Town. Follow-up of participants will continue until Oct/November 2011.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1.Isoniazid (INH) | Experimental | Drug: isoniazidA self-administered daily dose of 5mg/kg of Isoniazid (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) |
| 2. Placebo | Placebo comparator | Drug: PlaceboA self-administered daily dose of 5mg/kg of placebo for 12months (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and female attendees (age ≥18yo) of the Ubuntu HIV and ARV Clinic identified as eligible for the ARV programme will be invited to participate.
- Willingness to participate
- Able to engage in informed consent procedures
Key exclusion criteria (8 listed)
- Evidence of active TB or suspicion of active TB as determined by a symptoms screening algorithm.
- Current TB chemotherapy ( TB treatment completed in the preceding 30 days will not be an exclusion)
- Current or previous treatment of latent TB infection since HIV infection (any duration)
- Current treatment with fluoroquinolones or other antibiotics with significant anti-tuberculous activity currently being used to treat TB in South Africa
- Past reaction/intolerance to INH.
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 |
|---|---|---|
| isoniazidA self-administered daily dose of 5mg/kg of Isoniazid or placebo for 12months(300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) | Drug | 1.Isoniazid (INH) |
| PlaceboA self-administered dose of 5mg/kg of placebo (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg) | Drug | 2. Placebo |
Primary outcome
Rate of development of TB (microbiologically confirmed TB or highly probable TB) during the 36 month risk period
Time frame: Patients are assessed for TB one two monthly at each ART re-fill appointment
5 secondary outcomes
Rate of drug toxicity (specifically, peripheral neuropathy, hepatitis +/-raised ALT grade III or worse and allergic rashes grade III or worse
Time frame: during the intervention period (ALT determined at baseline, 1, 2 and 3 months and then 3-monthly. the last safety determination is at 12 months post initiation of the study drug)
Proportions adhering to study drug and HAART at the end of each study year as measured by pharmacy refills
Time frame: 1 month to two monthly, depending on the individual patient's clinic appointment
Rate of development of INH monoresistance during the 36 month risk period.
Time frame: 36 months
Death
Time frame: 36 months
Worsening ART outcomes (virological and immunological failure)
Time frame: CD4+count and viral load are assessed as per clinic protocol (6 monthly post ART initiation)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2012.
- Derived from this study: PubMed 24835842Rangaka MX, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, van Cutsem G, Wilkinson KA, Goliath R, Mathee S, Goemaere E, Maartens G. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial. Lancet. 2014 Aug 23;384(9944):682-90. doi: 10.1016/S0140-6736(14)60162-8. Epub 2014 May 13.
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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.
Gary Maartens (overall PI), FCP principal investigator
University of Cape Town
Eric Goemaere (co-investigator), MBBS study director
Medecins Sans Frontieres, Netherlands
Molebogeng X Rangaka (Lead Investigator), MBChB study director
University of Cape Town
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing isoniazid in people with Tuberculosis and Latent Tuberculosis Infection, run by University of Cape Town at 1 site in South Africa.
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 3 inclusion and 8 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 17 Jul 2012. 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 South Africa. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of development of TB (microbiologically confirmed TB or highly probable TB) during the 36 month risk period (time frame: Patients are assessed for TB one two monthly at each ART re-fill appointment). 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 NCT00463086, which also lists 1 linked publication.
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 17 Jul 2012.