TuberculosisPhase 2PHINXNCT05124678
Pharmacogenetics-guided Isoniazid Dosing in TB-HIV
A Phase 2 study testing Isoniazid Tablets in people with Tuberculosis, run by Makerere University at 1 site in Uganda.
Trial summary
The current TB treatment as recommended by World Health Organization (WHO) although capable of achieving 85% cure rates, has limitations, in particular drug interactions, toxicities, and the long treatment duration which increases the possibility of nonadherence. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUganda
- Study dates
- 7 Dec 2021to 30 Jun 2022
- Phase
- Phase 2
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Age of ≥18 years
- Bacteriologically confirmed pulmonary TB (determined by Xpert, culture, or microscopy)
- Confirmed HIV-1 infection.
- On TB treatment for ≤ 7 days at the time of enrolment (Within this time, the patient is still expected to have mycobacteria present in sputum and will provide enough time to conduct screening procedures)
Who cannot join
- TB infection of any organ/systems requiring TB treatment longer than 6 months
- Pregnancy
- Decompensated liver disease and/or aminotransferases >2.5 x ULN
Trial locations and contacts
1 site in 1 country.
Uganda1 site, 1 recruiting
- Recruiting
Infectious Diseases Institute
Kampala, 256
Christine Sekaggya-Wiltshire, MBChB, PhD, csekaggya@idi.co.ug
Christine Sekaggya-Wiltshire, MBChB, PhD
About this study
Official title: A Phase II Trial to Describe the Pharmacokinetics, Safety and Efficacy of Pharmacogenetics-guided Dosing of Isoniazid in Patients With HIV-associated TB
The current TB treatment as recommended by World Health Organization (WHO) although capable of achieving 85% cure rates, has limitations, in particular drug interactions, toxicities, and the long treatment duration which increases the possibility of nonadherence.
Sub-therapeutic isoniazid concentrations were demonstrated in several studies, including our previous work, carried out among patients with tuberculosis receiving the standard dose (5mg/kg) of isoniazid. The investigators found 78% of patients with HIV had isoniazid concentrations below the recommended threshold. Malabsorption, drug-drug interactions, poor adherence due to high pill burden may contribute to this. Pharmacogenetic variation may compound these factors; isoniazid displays inter-individual variation in serum concentrations and clearance due to differences in individual acetylator status.
Read more
While patients who metabolize isoniazid slowly (slow acetylators) are at a higher risk of high drug concentrations and toxicities, fast acetylators are more likely to have sub-therapeutic isoniazid concentrations.
In other studies, insufficient exposure with isoniazid, one of the cornerstone drugs for TB treatment, has been associated with delayed sputum clearance, development of drug resistance, and treatment failure.
Isoniazid is metabolized by the enzyme N-acetyl transferase, which in turn is controlled by the N-acetyl transferase-2 (NAT-2) gene. Polymorphisms in this gene are responsible for the N-acetylation phenotypes, with the distribution of NAT-2 fast, intermediate, and slow acetylators being highly variable especially among African populations.
Given that NAT2 acetylator status explains most of the variability in INH exposures, knowledge of NAT2 status may be a simpler way to select the right dose for individual patients. The investigators will therefore provide higher doses to fast acetylators and compare the isoniazid pharmacokinetics in these patients to slow acetylators who receive the standard dose, who are more likely to already be achieving target concentrations.
Read the detailed description
N-acetyl transferase genotyping will be performed on HIV infected patients diagnosed with T B. Slow acetylators will be initiated on the standard dose of isoniazid (5mg/kg) while fast and intermediate acetylators will be initiated on 10mg/kg of isoniazid. All other TB drugs will be given at their standard doses.
Monitoring for toxicities will be performed every two weeks (including ALT and screening for peripheral neuropathy) and isoniazid concentrations will be measured four weeks after initiating treatment at Ohr, 30mins, 1 hr, Thr and 4hr following observed drug intake.
Patients will be continued on standard dose isoniazid after completing the first 8 weeks of treatment (intensive phase).
Sputum cultures for mycobacteria will be performed at baseline, week 2, 4 and week 8. TB treatment outcome will be assessed after 6 months of treatment.
Non-linear mixed effects modelling will be used to model PK-PD data taking into account clinical and demographic factors like age, sex and BMI. The investigators will develop a model to establish the population parameters for isoniazid (for example clearance, absorption rate constant and volume of distribution) and the variability around these primary PK parameters. The investigators will then use the model to derive secondary PK parameters, namely area under the concentration-time curve (AUC) and maximum concentrations (Cmax) of isoniazid for each participant. The investigators will compare the PK parameters of isoniazid in fast/intermediate acetylators taking 10mg/kg and slow acetylators taking 5mg/kg of isoniazid.
In addition to the main objectives of the study, the investigators will also compare the PK in patients in the PG guided isoniazid dosing group to those in the historical cohort while matching for NAT2 status, age and sex. In the historical cohort, NAT-2 acetlyator genotyping was performed but patients received standard dosing regardless of NAT-2 acetylator status. In this trial, the investigators will use pharmacogenetic guided therapy for all participants. The investigators will therefore be able to compare the pharmacokinetic data above, safety and efficacy in patients who received pharmacogenetic therapy and those who did not.
The investigators will use PK-PD models to describe the relationship between concentrations and pharmacodynamic data (including toxicities and sputum conversion at week 8) in patients on the different doses. In addition to this, the investigators will also make this same comparison for patients in this study and those who did not receive PG guided therapy from the historical cohort. The investigators will also compare the number of grade 3-5 adverse events and time to sputum culture conversion in patients in patients who did and did not receive PG guided therapy while matching for NAT2 status, age and sex
- Conditions
- Tuberculosis
- Being tested
- Isoniazid Tablets
- Keywords
- Pharmacokinetics, Pharmacogenetics, High-dose Isoniazid
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid TabletsDrug
Also called INH
High dose of isoniazid
| Study group | Role | What they receive |
|---|---|---|
| Fast/intermediate acetylators | Experimental | Participants in this arm have fast/intermediate acetylator status from NAT2 genotyping.
In the Intensive phase (Month 1-2) of treatment, they will receive; Oral Isoniazid 10mg/kg/day + Rifampicin, Ethambutol and Pyrazinamide at standard dose.
In the continuation phase (Month 3 - 6 ) of treatment, they will receive; Oral Isoniazid 5mg/kg/day +Rifampicin at standard dose Receives: Drug: Isoniazid Tablets |
| Slow acetylators | No intervention | Participants in this arm have a slow acetylator status from NAT2 genotyping. They will receive the standard of care. In the Intensive phase (Month 1-2) of treatment, they will receive; Oral Isoniazid 5mg/kg/day + Rifampicin, Ethambutol and Pyrazinamide at standard dose. In the continuation phase (Month 3 - 6 ) of treatment, they will receive; Oral Isoniazid 5mg/kg/day +Rifampicin at standard dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the maximum concentrations of isoniazid stratified by NAT2 group
Maximum concentrations (Cmax)
Measured: Week 4 of treatment
Estimate the area under the concentration-time curve of isoniazid stratified by NAT2 group
Area under the concentration-time curve (AUC)
Measured: Week 4 of treatment
Estimate the of Clearance isoniazid stratified by NAT2 group
Clearance (L/h)
Measured: Week 4 of treatment
Estimate the Volume of distribution of isoniazid stratified by NAT2 group
Volume of distribution (L)
Measured: Week 4 of treatment
Secondary outcomes (4)
Drug-induced hepatotoxicity
Grade 2 or higher elevation in ALT or total bilirubin (drug-induced hepatotoxicity)
Measured: Up to week 8 of treatment
Other drug-related adverse events
Other grade 2 or higher adverse events
Measured: Up to week 8 of treatment
Peripheral neuropathy
Grade 2 or higher peripheral neuropathy
Measured: Up to week 8 of treatment
Sputum culture conversion at week 8
Proportion of patients who remain sputum positive
Measured: Up to week 8 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2021
- Study start7 Dec 2021
- Primary completion30 Mar 2022 (estimated)
- Study completion30 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christine Sekaggya-Wiltshire, MBChB, PhD, Principal investigator, Infectious Diseases Institute-Kampala
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05124678
- Sponsor's protocol ID
- IDI SRC Ref:16/2020
- Acronym
- PHINX
- Status last verified
- Oct 2021
- First submitted
- 1 Oct 2021
- Last updated
- 25 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual patient data (IPD) will made available to other researchers for further analysis or met-analysis upon reasonable request to the investigators.
Publications
Adams LV, Mahlalela N, Talbot EA, Pasipamire M, Ginindza S, Calnan M, Haumba S. High completion rates of isoniazid preventive therapy among persons living with HIV in Swaziland. Int J Tuberc Lung Dis. 2017 Oct 1;21(10):1127-1132. doi: 10.5588/ijtld.16.0946.
PubMed 28911356World Health Organization, Guildelines for treatment of Tuberculosis. 2013.
Han T. Effectiveness of standard short-course chemotherapy for treating tuberculosis and the impact of drug resistance on its outcome. JBI Libr Syst Rev. 2006;4(3):1-27. doi: 10.11124/01938924-200604030-00001.
PubMed 27819814Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC, Wells CD, Reingold AL, Kenyon TA, Moeti TL, Tappero JW. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009 Jun 15;48(12):1685-94. doi: 10.1086/599040.
PubMed 19432554McIlleron H, Rustomjee R, Vahedi M, Mthiyane T, Denti P, Connolly C, Rida W, Pym A, Smith PJ, Onyebujoh PC. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines. Antimicrob Agents Chemother. 2012 Jun;56(6):3232-8. doi: 10.1128/AAC.05526-11. Epub 2012 Mar 12.
PubMed 22411614Park JS, Lee JY, Lee YJ, Kim SJ, Cho YJ, Yoon HI, Lee CT, Song J, Lee JH. Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome. Antimicrob Agents Chemother. 2015 Oct 12;60(1):92-8. doi: 10.1128/AAC.00693-15. Print 2016 Jan.
PubMed 26459901Peloquin CA, Nitta AT, Burman WJ, Brudney KF, Miranda-Massari JR, McGuinness ME, Berning SE, Gerena GT. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996 Sep;30(9):919-25. doi: 10.1177/106002809603000901.
PubMed 8876848Sekaggya-Wiltshire C, von Braun A, Lamorde M, Ledergerber B, Buzibye A, Henning L, Musaazi J, Gutteck U, Denti P, de Kock M, Jetter A, Byakika-Kibwika P, Eberhard N, Matovu J, Joloba M, Muller D, Manabe YC, Kamya MR, Corti N, Kambugu A, Castelnuovo B, Fehr JS. Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations. Clin Infect Dis. 2018 Aug 16;67(5):708-716. doi: 10.1093/cid/ciy179.
PubMed 29514175Ding J, Thuy Thuong Thuong N, Pham TV, Heemskerk D, Pouplin T, Tran CTH, Nguyen MTH, Nguyen PH, Phan LP, Nguyen CVV, Thwaites G, Tarning J. Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis. Clin Pharmacol Ther. 2020 Apr;107(4):1023-1033. doi: 10.1002/cpt.1783. Epub 2020 Feb 29.
PubMed 31956998Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980 Jun;121(6):939-49. doi: 10.1164/arrd.1980.121.6.939. No abstract available.
PubMed 6774638Sloan D: Pharmacokinetic Variability in TB Therapy: Associations with HIV and Effect on Outcome. In: Conference on Retroviruses and Opportunistic Infections. Boston, Massachusetts, U.S.A; 2014
Mah A, Kharrat H, Ahmed R, Gao Z, Der E, Hansen E, Long R, Kunimoto D, Cooper R. Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients. Int J Tuberc Lung Dis. 2015 Feb;19(2):210-5. doi: 10.5588/ijtld.14.0405.
PubMed 25574921Cordes H, Thiel C, Aschmann HE, Baier V, Blank LM, Kuepfer L. A Physiologically Based Pharmacokinetic Model of Isoniazid and Its Application in Individualizing Tuberculosis Chemotherapy. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6134-45. doi: 10.1128/AAC.00508-16. Print 2016 Oct.
PubMed 27480867Katiyar SK, Bihari S, Prakash S, Mamtani M, Kulkarni H. A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008 Feb;12(2):139-45.
PubMed 18230245Sekaggya-Wiltshire C, von Braun A, Scherrer AU, Manabe YC, Buzibye A, Muller D, Ledergerber B, Gutteck U, Corti N, Kambugu A, Byakika-Kibwika P, Lamorde M, Castelnuovo B, Fehr J, Kamya MR. Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients. J Antimicrob Chemother. 2017 Apr 1;72(4):1172-1177. doi: 10.1093/jac/dkw534.
PubMed 28108678
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial to Describe the Pharmacokinetics, Safety and Efficacy of Pharmacogenetics-guided Dosing of Isoniazid in Patients With HIV-associated TB
- ClinicalTrials.gov ID
- NCT05124678
- Acronym / sponsor ID
- PHINX / IDI SRC Ref:16/2020
- Conditions
- Tuberculosis
- Keywords
- Pharmacokinetics, Pharmacogenetics, High-dose Isoniazid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Study start
- 7 Dec 2021 (actual)
- Primary completion
- 30 Mar 2022 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 18 Nov 2021 (actual)
- 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 current TB treatment as recommended by World Health Organization (WHO) although capable of achieving 85% cure rates, has limitations, in particular drug interactions, toxicities, and the long treatment duration which increases the possibility of nonadherence.
Sub-therapeutic isoniazid concentrations were demonstrated in several studies, including our previous work, carried out among patients with tuberculosis receiving the standard dose (5mg/kg) of isoniazid. The investigators found 78% of patients with HIV had isoniazid concentrations below the recommended threshold. Malabsorption, drug-drug interactions, poor adherence due to high pill burden may contribute to this. Pharmacogenetic variation may compound these factors; isoniazid displays inter-individual variation in serum concentrations and clearance due to differences in individual acetylator status.
While patients who metabolize isoniazid slowly (slow acetylators) are at a higher risk of high drug concentrations and toxicities, fast acetylators are more likely to have sub-therapeutic isoniazid concentrations.
In other studies, insufficient exposure with isoniazid, one of the cornerstone drugs for TB treatment, has been associated with delayed sputum clearance, development of drug resistance, and treatment failure.
Isoniazid is metabolized by the enzyme N-acetyl transferase, which in turn is controlled by the N-acetyl transferase-2 (NAT-2) gene. Polymorphisms in this gene are responsible for the N-acetylation phenotypes, with the distribution of NAT-2 fast, intermediate, and slow acetylators being highly variable especially among African populations.
Given that NAT2 acetylator status explains most of the variability in INH exposures, knowledge of NAT2 status may be a simpler way to select the right dose for individual patients. The investigators will therefore provide higher doses to fast acetylators and compare the isoniazid pharmacokinetics in these patients to slow acetylators who receive the standard dose, who are more likely to already be achieving target concentrations.
Detailed description
N-acetyl transferase genotyping will be performed on HIV infected patients diagnosed with T B. Slow acetylators will be initiated on the standard dose of isoniazid (5mg/kg) while fast and intermediate acetylators will be initiated on 10mg/kg of isoniazid. All other TB drugs will be given at their standard doses.
Monitoring for toxicities will be performed every two weeks (including ALT and screening for peripheral neuropathy) and isoniazid concentrations will be measured four weeks after initiating treatment at Ohr, 30mins, 1 hr, Thr and 4hr following observed drug intake.
Patients will be continued on standard dose isoniazid after completing the first 8 weeks of treatment (intensive phase).
Sputum cultures for mycobacteria will be performed at baseline, week 2, 4 and week 8. TB treatment outcome will be assessed after 6 months of treatment.
Non-linear mixed effects modelling will be used to model PK-PD data taking into account clinical and demographic factors like age, sex and BMI. The investigators will develop a model to establish the population parameters for isoniazid (for example clearance, absorption rate constant and volume of distribution) and the variability around these primary PK parameters. The investigators will then use the model to derive secondary PK parameters, namely area under the concentration-time curve (AUC) and maximum concentrations (Cmax) of isoniazid for each participant. The investigators will compare the PK parameters of isoniazid in fast/intermediate acetylators taking 10mg/kg and slow acetylators taking 5mg/kg of isoniazid.
In addition to the main objectives of the study, the investigators will also compare the PK in patients in the PG guided isoniazid dosing group to those in the historical cohort while matching for NAT2 status, age and sex. In the historical cohort, NAT-2 acetlyator genotyping was performed but patients received standard dosing regardless of NAT-2 acetylator status. In this trial, the investigators will use pharmacogenetic guided therapy for all participants. The investigators will therefore be able to compare the pharmacokinetic data above, safety and efficacy in patients who received pharmacogenetic therapy and those who did not.
The investigators will use PK-PD models to describe the relationship between concentrations and pharmacodynamic data (including toxicities and sputum conversion at week 8) in patients on the different doses. In addition to this, the investigators will also make this same comparison for patients in this study and those who did not receive PG guided therapy from the historical cohort. The investigators will also compare the number of grade 3-5 adverse events and time to sputum culture conversion in patients in patients who did and did not receive PG guided therapy while matching for NAT2 status, age and sex
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fast/intermediate acetylators | Experimental | Drug: Isoniazid TabletsParticipants in this arm have fast/intermediate acetylator status from NAT2 genotyping. In the Intensive phase (Month 1-2) of treatment, they will receive; Oral Isoniazid 10mg/kg/day + Rifampicin, Ethambutol and Pyrazinamide at standard dose. In the continuation phase (Month 3 - 6 ) of treatment, they will receive; Oral Isoniazid 5mg/kg/day +Rifampicin at standard dose |
| Slow acetylators | No intervention | –Participants in this arm have a slow acetylator status from NAT2 genotyping. They will receive the standard of care. In the Intensive phase (Month 1-2) of treatment, they will receive; Oral Isoniazid 5mg/kg/day + Rifampicin, Ethambutol and Pyrazinamide at standard dose. In the continuation phase (Month 3 - 6 ) of treatment, they will receive; Oral Isoniazid 5mg/kg/day +Rifampicin at standard dose |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Age of ≥18 years
- Bacteriologically confirmed pulmonary TB (determined by Xpert, culture, or microscopy)
- Confirmed HIV-1 infection.
Key exclusion criteria (3 listed)
- TB infection of any organ/systems requiring TB treatment longer than 6 months
- Pregnancy
- Decompensated liver disease and/or aminotransferases >2.5 x ULN
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 TabletsAlso: INHHigh dose of isoniazid | Drug | Fast/intermediate acetylators |
Primary outcome
Estimate the maximum concentrations of isoniazid stratified by NAT2 group
Time frame: Week 4 of treatment
Maximum concentrations (Cmax)
Estimate the area under the concentration-time curve of isoniazid stratified by NAT2 group
Time frame: Week 4 of treatment
Area under the concentration-time curve (AUC)
Estimate the of Clearance isoniazid stratified by NAT2 group
Time frame: Week 4 of treatment
Clearance (L/h)
Estimate the Volume of distribution of isoniazid stratified by NAT2 group
Time frame: Week 4 of treatment
Volume of distribution (L)
4 secondary outcomes
Drug-induced hepatotoxicity
Time frame: Up to week 8 of treatment
Other drug-related adverse events
Time frame: Up to week 8 of treatment
Peripheral neuropathy
Time frame: Up to week 8 of treatment
Sputum culture conversion at week 8
Time frame: Up to week 8 of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2022.
- Background: PubMed 28911356Adams LV, Mahlalela N, Talbot EA, Pasipamire M, Ginindza S, Calnan M, Haumba S. High completion rates of isoniazid preventive therapy among persons living with HIV in Swaziland. Int J Tuberc Lung Dis. 2017 Oct 1;21(10):1127-1132. doi: 10.5588/ijtld.16.0946.
- BackgroundWorld Health Organization, Guildelines for treatment of Tuberculosis. 2013.
- Background: PubMed 27819814Han T. Effectiveness of standard short-course chemotherapy for treating tuberculosis and the impact of drug resistance on its outcome. JBI Libr Syst Rev. 2006;4(3):1-27. doi: 10.11124/01938924-200604030-00001.
- Background: PubMed 19432554Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC, Wells CD, Reingold AL, Kenyon TA, Moeti TL, Tappero JW. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009 Jun 15;48(12):1685-94. doi: 10.1086/599040.
- Background: PubMed 22411614McIlleron H, Rustomjee R, Vahedi M, Mthiyane T, Denti P, Connolly C, Rida W, Pym A, Smith PJ, Onyebujoh PC. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines. Antimicrob Agents Chemother. 2012 Jun;56(6):3232-8. doi: 10.1128/AAC.05526-11. Epub 2012 Mar 12.
- Background: PubMed 26459901Park JS, Lee JY, Lee YJ, Kim SJ, Cho YJ, Yoon HI, Lee CT, Song J, Lee JH. Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome. Antimicrob Agents Chemother. 2015 Oct 12;60(1):92-8. doi: 10.1128/AAC.00693-15. Print 2016 Jan.
- Background: PubMed 8876848Peloquin CA, Nitta AT, Burman WJ, Brudney KF, Miranda-Massari JR, McGuinness ME, Berning SE, Gerena GT. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996 Sep;30(9):919-25. doi: 10.1177/106002809603000901.
- Background: PubMed 29514175Sekaggya-Wiltshire C, von Braun A, Lamorde M, Ledergerber B, Buzibye A, Henning L, Musaazi J, Gutteck U, Denti P, de Kock M, Jetter A, Byakika-Kibwika P, Eberhard N, Matovu J, Joloba M, Muller D, Manabe YC, Kamya MR, Corti N, Kambugu A, Castelnuovo B, Fehr JS. Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations. Clin Infect Dis. 2018 Aug 16;67(5):708-716. doi: 10.1093/cid/ciy179.
- Background: PubMed 31956998Ding J, Thuy Thuong Thuong N, Pham TV, Heemskerk D, Pouplin T, Tran CTH, Nguyen MTH, Nguyen PH, Phan LP, Nguyen CVV, Thwaites G, Tarning J. Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis. Clin Pharmacol Ther. 2020 Apr;107(4):1023-1033. doi: 10.1002/cpt.1783. Epub 2020 Feb 29.
- Background: PubMed 6774638Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980 Jun;121(6):939-49. doi: 10.1164/arrd.1980.121.6.939. No abstract available.
- BackgroundSloan D: Pharmacokinetic Variability in TB Therapy: Associations with HIV and Effect on Outcome. In: Conference on Retroviruses and Opportunistic Infections. Boston, Massachusetts, U.S.A; 2014
- Background: PubMed 25574921Mah A, Kharrat H, Ahmed R, Gao Z, Der E, Hansen E, Long R, Kunimoto D, Cooper R. Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients. Int J Tuberc Lung Dis. 2015 Feb;19(2):210-5. doi: 10.5588/ijtld.14.0405.
- Individual participant dataSharing planned: Yes. Individual patient data (IPD) will made available to other researchers for further analysis or met-analysis upon reasonable request to the investigators.
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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.
Christine Sekaggya-Wiltshire, MBChB, PhD principal investigator
Infectious Diseases Institute-Kampala
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isoniazid Tablets in people with Tuberculosis, run by Makerere University 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 6 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 25 Jan 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christine Sekaggya-Wiltshire, MBChB, PhD (256772479791, csekaggya@idi.co.ug), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimate the maximum concentrations of isoniazid stratified by NAT2 group (time frame: Week 4 of treatment). The study lists 4 primary outcomes in all. 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 NCT05124678, which also lists 21 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 25 Jan 2022.