Trial Outcomes & Findings for Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) (NCT NCT03302299)
NCT ID: NCT03302299
Last Updated: 2023-10-19
Results Overview
Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period.
COMPLETED
PHASE4
302 participants
Hepatotoxicity occurring during the six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.
2023-10-19
Participant Flow
Participants were recruited from an HIV clinic from April 2017 through December 2019.
Participant milestones
| Measure |
INH and Vitamin B6
This was a single arm trial with a recruitment goal of 200 participants who reported current (prior 3 months) alcohol use, and 100 prior year abstinence from alcohol use. All participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Overall Study
STARTED
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302
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Overall Study
Completed 3 Month Visit
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295
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Overall Study
Completed 6 Month Visit
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289
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Overall Study
COMPLETED
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301
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
INH and Vitamin B6
This was a single arm trial with a recruitment goal of 200 participants who reported current (prior 3 months) alcohol use, and 100 prior year abstinence from alcohol use. All participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Overall Study
Protocol Violation
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1
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Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
INH and Vitamin B6
n=301 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Age, Continuous
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40 year
n=301 Participants
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Sex: Female, Male
Female
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154 Participants
n=301 Participants
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Sex: Female, Male
Male
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147 Participants
n=301 Participants
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Region of Enrollment
Uganda
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301 participants
n=301 Participants
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PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
INH and Vitamin B6
n=301 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity
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8.3 percent
Interval 5.4 to 12.0
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SECONDARY outcome
Timeframe: Six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.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.
Outcome measures
| Measure |
INH and Vitamin B6
n=301 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Number of Participants Who Discontinued Treatment
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32 Participants
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SECONDARY outcome
Timeframe: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter)Population: 279/301 participants completed at least 1 study visit at either 3 or 6 months while on INH and are included here. 275 participants were included at 3 months; 264 participants were included at 6 months.
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.
Outcome measures
| Measure |
INH and Vitamin B6
n=279 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Percentage of Participants With Suboptimal INH Medication Adherence
at 3 months
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31.3 percentage of participants
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Percentage of Participants With Suboptimal INH Medication Adherence
at 6 months
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43.9 percentage of participants
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SECONDARY outcome
Timeframe: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INHPopulation: 290 unique participants are included here. 285 individuals are included at 3 months; 268 individuals are included at 6 months. Participants with missed visits or who were not taking INH (ie. due to either a temporary pause due to the COVID lockdown in Uganda, or because they were discontinued) were excluded.
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.
Outcome measures
| Measure |
INH and Vitamin B6
n=290 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days
at 3 months
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30 days
Interval 28.0 to 30.0
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Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days
at 6 months
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30 days
Interval 27.0 to 30.0
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SECONDARY outcome
Timeframe: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INHPopulation: 280 unique participants are included here. 279 individuals are included at 3 months; 260 individuals are included at 6 months. Participants who reported no INH use in the prior 30 days were excluded.
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.
Outcome measures
| Measure |
INH and Vitamin B6
n=280 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Good
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41 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Excellent
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160 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Very good
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79 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Good
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38 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Fair
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0 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Poor
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2 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 3 months · Very poor
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0 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Excellent
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124 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Very good
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90 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Fair
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4 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Poor
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0 Participants
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Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale
At 6 months · Very poor
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1 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: Measured at 3- and 6- months after INH initiationPopulation: We had funding to analyze the first shipped batch of hair (n=161 total visits, representing 97 unique participants) for INH.
INH concentration in hair (pmol/mg) will be measured at 3- and 6- months during INH therapy.
Outcome measures
| Measure |
INH and Vitamin B6
n=97 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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INH Concentration in Hair: (INH Pmol + Acetyl INH Pmol) Per mg of Hair
at 3 months
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36.0 pmol/mg
Interval 18.7 to 63.3
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INH Concentration in Hair: (INH Pmol + Acetyl INH Pmol) Per mg of Hair
at 6 months
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37.8 pmol/mg
Interval 13.7 to 60.4
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OTHER_PRE_SPECIFIED outcome
Timeframe: Study screening visitPopulation: People who completed liver transaminase testing as part of the screening for this study.
Alanine transaminase (ALT) or aspartate transaminase (AST) elevations (\>2x the upper limit of normal) at study screening
Outcome measures
| Measure |
INH and Vitamin B6
n=1303 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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Number of Participants With Alanine Transaminase (ALT) or Aspartate Transaminase (AST) Elevations at Study Screening
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80 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: Study screening visitPopulation: People who completed tuberculin skin testing (TST) as part of the study screening. People who did not return for the TST reading within the required window of 48-72 hours are excluded here.
Latent tuberculosis assessed at screening via tuberculin skin testing (TST). A TST induration \>=5mm was considered positive for latent tuberculosis.
Outcome measures
| Measure |
INH and Vitamin B6
n=1156 Participants
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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Number of Participants With Latent Tuberculosis at Study Screening.
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308 Participants
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Adverse Events
INH and Vitamin B6
Serious adverse events
| Measure |
INH and Vitamin B6
n=301 participants at risk
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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Hepatobiliary disorders
Elevated AST or ALT
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2.0%
6/301 • Number of events 6 • Data were collected over the course of study participation, for a maximum of 42 months.
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Injury, poisoning and procedural complications
Accident
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Death
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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Infections and infestations
Septicemia
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Blood and lymphatic system disorders
Low hemoglobin
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Cardiac disorders
High blood pressure
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Hospitalization
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Other adverse events
| Measure |
INH and Vitamin B6
n=301 participants at risk
This was a single arm trial; participants were given 300 mg INH daily by mouth for 6 months, and 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months.
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|---|---|
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Hepatobiliary disorders
Grade 3: AST or ALT elevation
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6.0%
18/301 • Number of events 18 • Data were collected over the course of study participation, for a maximum of 42 months.
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Hepatobiliary disorders
Grade 2: AST or ALT elevation
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20.6%
62/301 • Number of events 71 • Data were collected over the course of study participation, for a maximum of 42 months.
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Immune system disorders
PPD hypersensitivity
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1.00%
3/301 • Number of events 3 • Data were collected over the course of study participation, for a maximum of 42 months.
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Nervous system disorders
Paresthesias
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Fatigue
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Gastrointestinal disorders
Abdominal pain
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Skin and subcutaneous tissue disorders
Skin rash
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Vomiting
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Nausea
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Dizziness
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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Immune system disorders
Angioedema
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Eye disorders
Allergic conjuctivitis
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Nervous system disorders
Shooting pains
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Visual changes (blurring)
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Hypotension
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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General disorders
Poor appetite
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Injury, poisoning and procedural complications
Physically assaulted
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Injury, poisoning and procedural complications
Soft tissue injury
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0.33%
1/301 • Number of events 1 • Data were collected over the course of study participation, for a maximum of 42 months.
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Cardiac disorders
Hypertension
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0.66%
2/301 • Number of events 2 • Data were collected over the course of study participation, for a maximum of 42 months.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place