Trial · NCT01936831
High-Dose Isoniazid Among Adult Patients With Different Genetic Variants of INH-Resistant Tuberculosis (TB)
NCT01936831, Phase 2, Completed, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections; results first posted 2023-02-17
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. High-Dose Isoniazid Among Adult Patients With Different Genetic Variants of INH-Resistant Tuberculosis (TB). Trials, record NCT01936831. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01936831
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- High-Dose Isoniazid Among Adult Patients With Different Genetic Variants of INH-Resistant Tuberculosis (TB)
- NCT number
- NCT01936831
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 282 participants, actual
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Conditions
- Tuberculosis
- Interventions
- Isoniazid, Vitamin B6
- First posted
- 2013-09-06
- Last updated
- 2023-02-17
- Results first posted
- 2023-02-17
Source ClinicalTrials.gov
Registered outcomes12
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Daily Change in log10 Colony-forming Unit (CFU) | Measured at baseline and Day 7 | Negative daily change in log10 CFU indicate decreases in bacterial burden over the 7 day period. Defined as EBA0-7(CFU) = \[Day 7 log10 CFU per mL - baseline log10 CFU per mL\]/7. The baseline measure is the mean of the pre-entry visit and entry visit sputum colony counts. |
| Primary | Daily Change in Time to Positivity (TTP) | Measured at baseline and Day 7 | The time to positivity (TTP) measures growth of mycobacterium tuberculosis using MGIT assay in hours. Higher values of daily change in TTP indicate greater decrease in bacterial burden over the 7 day period and is therefore better. Daily change is defined as EBA0-7(TTP) = \[Day 7 TTP - Baseline TTP\]/7. Baseline is the mean of the pre-entry visit and entry visit TTPs. |
| Primary | INH PK Parameter Area Under the Concentration Time Curve (AUC 0-24 Hours) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose, estimated through non-compartmental methods using the linear trapezoidal rule. |
| Primary | Number of Participants With Grade 2 or Higher Drug-related Adverse Clinical or Laboratory Events | Measured from entry through Day 21 | Post-entry, all new diagnoses, signs/symptoms and laboratory events of ≥Grade 2 that were assessed by the site as drug related. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used. |
| Secondary | INH PK Parameter Minimum Plasma Concentration (Cmin) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | Cmin defines minimum concentration observed over the 24 hours of the INH dosing interval. |
| Secondary | INH PK Parameter Maximum Plasma Concentration (Cmax) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | Cmax defines maximum concentration observed over the 24 hours of the INH dosing interval. |
| Secondary | INH Minimum Inhibitory Concentration (MIC) Against M. Tuberculosis Isolates | Day 0 | MIC are determined by phenotypic drug susceptibility testing (DST) based on spot sputum collected at Step 1 Day 0. For group 3 participants shown, MIC was tested using Thermofisher Sensititre MYCOTB plates. |
| Secondary | Proportions of Participants Estimated to Have a Drop in log10 CFU/mL at or Above 0.65 log10 CFU/mL. | From baseline through day 7 | Proportions of participants obtained through simulation using the estimated model who have a drop in log10 CFU/mL at or above the threshold of 0.65 log10 CFU/mL; 0.65 is half the drop in log10 CFU/mL observed in participants with DS-TB (Group 2) on day 7. A total of 10000 simulated pseudo-participants per arm were used based on data from the study participants. The NAT2 genotype distribution was based only on Group 1 and 2 participants since NAT2 genotype data was not available for Group 3. The simulations were run repeatedly. The point estimate of the proportion was based on the median proportion of the pseudo-individuals across the repeated simulations and the 90% confidence interval used the 5th and 95th percentiles of the proportion across the repeated simulations. |
| Secondary | Daily Change in log10 CFU Measured by Early- (EBA0-2) and Late-phase (EBA2-7) Individual-based Parameter Estimates From Nonlinear Models | At baseline, day 2, and day 7 | Negative daily change in log10 CFU indicate decreases in bacterial burden over the time period. The mean CFU are estimated using all values by fitting a biphasic regression models for each participant. The daily change for the first two days of treatment was calculated as EBA0-2 (CFU)= \[Day 2 log10 CFU per mL - baseline log10 CFU per mL\]/2. The daily change from day 2 to day 7 was calculated as EBA2-7 (CFU)= \[Day 7 log10 CFU per mL - Day 2 log10 CFU per mL\]/5. Baseline is the average of pre-entry and entry visits. |
| Secondary | Daily Change in TTP Measured by Early- (EBA0-2) and Late-phase (EBA2-7) Individual-based Parameter Estimates From Nonlinear Models | At baseline, day 2, and day 7 | The time to positivity (TTP) measures growth of mycobacterium tuberculosis using MGIT assay in hours. Higher values of daily change in TTP indicate greater decrease in bacterial burden over the time period and is therefore better. The mean log transformed TTP are estimated using all values by fitting a biphasic regression models for each participant. The daily change over the first two days of treatment is calculated as EBA0-2 (TTP)= \[Day 2 TTP - baseline TTP\]/2. The daily change from Day 2 to Day 7 is calculated as EBA2-7 (TTP)= \[Day 7 TTP - Day 2 TTP\]/5. Baseline is the average of pre-evaluation and entry visits. |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 registered outcomesOutcomes12
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Daily Change in log10 Colony-forming Unit (CFU) | Measured at baseline and Day 7 | Participants who took at least one dose of study treatment in Step 2 in Groups 1 and 2. CFU was not collected for Group 3. Participants who had missing Baseline or Day 7 CFU counts were not included. | log10 CFU per mL sputum per day | MEAN |
| PRIMARY | Daily Change in Time to Positivity (TTP) | Measured at baseline and Day 7 | Participants who took at least one dose of study treatment in Step 2. Participants who had missing Baseline or Day 7 TTP counts were not included. | hours per day | MEAN |
| PRIMARY | INH PK Parameter Area Under the Concentration Time Curve (AUC 0-24 Hours) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | Participants in each treatment dose arm with intensive PK results in Step 2. | ug*hr/mL | MEDIAN |
| PRIMARY | Number of Participants With Grade 2 or Higher Drug-related Adverse Clinical or Laboratory Events | Measured from entry through Day 21 | Participants who took at least one dose of study treatment in Step 2. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | INH PK Parameter Minimum Plasma Concentration (Cmin) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | Participants in each treatment dose arm with intensive PK results in Step 2. | ug/mL | MEDIAN |
| SECONDARY | INH PK Parameter Maximum Plasma Concentration (Cmax) | Intensive INH PK samples collected on Day 6 of INH initiation at sample times pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose. | Participants in each treatment dose arm with intensive PK results in Step 2. | ug/mL | MEDIAN |
| SECONDARY | INH Minimum Inhibitory Concentration (MIC) Against M. Tuberculosis Isolates | Day 0 | Step 1 participants in Group 3 for whom MIC results were available and tested using Thermofisher Sensititre MYCOTB plates. MIC was not done using Thermofisher Sensititre MYCOTB plates for participants enrolled under versions 1.0 and 2.0 of the protocol (including all Group 1 and 2 participants and many Group 3 participants). Three Group 3 Version 3 participants had missing MIC results. Note: Participants were not yet randomized to a treatment in Step 1 so all Group 3 participants are combined. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Proportions of Participants Estimated to Have a Drop in log10 CFU/mL at or Above 0.65 log10 CFU/mL. | From baseline through day 7 | Data from all participants were included in the modeling. | proportion of simulated participants | MEDIAN |
| SECONDARY | Daily Change in log10 CFU Measured by Early- (EBA0-2) and Late-phase (EBA2-7) Individual-based Parameter Estimates From Nonlinear Models | At baseline, day 2, and day 7 | Four participants were excluded from the analysis due to missing CFU values in Group 1-INH 10 mg (2), Group 1-INH 15mg (1), and Group 2 (1). CFU was not collected for Group 3. | log10 CFU per mL sputum per day | MEAN |
| SECONDARY | Daily Change in TTP Measured by Early- (EBA0-2) and Late-phase (EBA2-7) Individual-based Parameter Estimates From Nonlinear Models | At baseline, day 2, and day 7 | All available TTP results were used. | hours per day | MEAN |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 outcomesResults by group69
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Daily Change in log10 Colony-forming Unit (CFU) | Group 1: 5mg Cohort | -0.06 | Standard Deviation 0.14 | log10 CFU per mL sputum per day | |
| Daily Change in log10 Colony-forming Unit (CFU) | Group 1: 10mg Cohort | -0.18 | Standard Deviation 0.12 | log10 CFU per mL sputum per day | |
| Daily Change in log10 Colony-forming Unit (CFU) | Group 1: 15mg Cohort | -0.21 | Standard Deviation 0.15 | log10 CFU per mL sputum per day | |
| Daily Change in log10 Colony-forming Unit (CFU) | Group 2: 5mg Cohort | -0.15 | Standard Deviation 0.11 | log10 CFU per mL sputum per day | |
| Daily Change in Time to Positivity (TTP) | Group 1: 5mg Cohort | 3 | Standard Deviation 8 | hours per day | |
| Daily Change in Time to Positivity (TTP) | Group 1: 10mg Cohort | 8 | Standard Deviation 6 | hours per day | |
| Daily Change in Time to Positivity (TTP) | Group 1: 15mg Cohort | 10 | Standard Deviation 8 | hours per day | |
| Daily Change in Time to Positivity (TTP) | Group 2: 5mg Cohort | 10 | Standard Deviation 4 | hours per day | |
| Daily Change in Time to Positivity (TTP) | Group 3: 15mg Cohort | 2.0 | Standard Deviation 7.9 | hours per day | |
| Daily Change in Time to Positivity (TTP) | Group 3: 20mg Cohort | 4.6 | Standard Deviation 7.9 | hours per day |
1 to 10 of 69Source ClinicalTrials.gov
See all 69 results by groupParticipant flow54
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Step 1: Group Identification | STARTED | Group 1: inhA Mutation | 110 | |
| Step 1: Group Identification | STARTED | Group 2: Neither inhA Nor katG Mutations | 85 | |
| Step 1: Group Identification | STARTED | Group 3: katG Mutation | 87 | |
| Step 1: Group Identification | STARTED | Group 1: 5mg Cohort | 0 | |
| Step 1: Group Identification | STARTED | Group 1: 10mg Cohort | 0 | |
| Step 1: Group Identification | STARTED | Group 1: 15mg Cohort | 0 | |
| Step 1: Group Identification | STARTED | Group 2: 5mg Cohort | 0 | |
| Step 1: Group Identification | STARTED | Group 3: 15mg Cohort | 0 | |
| Step 1: Group Identification | STARTED | Group 3: 20mg Cohort | 0 | |
| Step 1: Group Identification | COMPLETED | Group 1: inhA Mutation | 110 |
1 to 10 of 54Source ClinicalTrials.gov
See all 54 participant flowAdverse events210
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 1- INH 5mg | 1 | 13 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 1- INH 10mg | 0 | 14 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 1- INH 15mg | 0 | 16 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 2- INH 5mg | 0 | 16 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 3- INH 15mg | 0 | 11 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Group 3- INH 20mg | 0 | 10 | |
| other | Palpitations | Cardiac disorders | Group 1- INH 5mg | 1 | 13 | |
| other | Palpitations | Cardiac disorders | Group 1- INH 10mg | 0 | 14 | |
| other | Palpitations | Cardiac disorders | Group 1- INH 15mg | 0 | 16 | |
| other | Palpitations | Cardiac disorders | Group 2- INH 5mg | 0 | 16 |
1 to 10 of 210Source ClinicalTrials.gov
See all 210 adverse eventsAdverse event totals18
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Group 1- INH 5mg | 0 | 13 |
| Total, all-cause mortality | Group 1- INH 10mg | 0 | 14 |
| Total, all-cause mortality | Group 1- INH 15mg | 0 | 16 |
| Total, all-cause mortality | Group 2- INH 5mg | 0 | 16 |
| Total, all-cause mortality | Group 3- INH 15mg | 0 | 11 |
| Total, all-cause mortality | Group 3- INH 20mg | 0 | 10 |
| Total, other adverse events | Group 1- INH 5mg | 12 | 13 |
| Total, other adverse events | Group 1- INH 10mg | 14 | 14 |
| Total, other adverse events | Group 1- INH 15mg | 15 | 16 |
| Total, other adverse events | Group 2- INH 5mg | 16 | 16 |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 adverse event totalsPapers3
The papers the trial lists on ClinicalTrials.gov.
Grants1
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years |
|---|---|---|---|---|---|
| UM1AI068636 | Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | CURRIER, JUDITH S.; ERON, JOSEPH J | UNIVERSITY OF CALIFORNIA LOS ANGELES | NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES | 2011 to 2025 |
Source NIH RePORTER
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01936831
GET https://conductscience.org/api/trials/v1/NCT01936831/results?page=2