Trial Outcomes & Findings for The Impact of Alcohol Consumption on Tuberculosis Treatment Outcomes (NCT NCT02840877)

NCT ID: NCT02840877

Last Updated: 2024-08-27

Results Overview

Time to sterilization/culture conversion during the first twelve weeks of treatment in patients with problem alcohol use compared to those without

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 303 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2024-08-27

Participant Flow

Participant milestones

Measure	TRUST Cohort TRUST Study Cohort
Baseline to 12 Weeks STARTED	303
Baseline to 12 Weeks COMPLETED	282
Baseline to 12 Weeks NOT COMPLETED	21
12 Weeks to 6 Months STARTED	282
12 Weeks to 6 Months COMPLETED	271
12 Weeks to 6 Months NOT COMPLETED	11
6 Months to 18 Months STARTED	271
6 Months to 18 Months COMPLETED	205
6 Months to 18 Months NOT COMPLETED	66

Reasons for withdrawal

Measure	TRUST Cohort TRUST Study Cohort
Baseline to 12 Weeks Withdrawal by Subject	11
Baseline to 12 Weeks Moved/Transferred out	5
Baseline to 12 Weeks Lost to Follow-up	2
Baseline to 12 Weeks Death	1
Baseline to 12 Weeks Changed treatment regimen, no longer on first line drugs.	1
Baseline to 12 Weeks Treatment extended due to bacterial meningitis.	1
12 Weeks to 6 Months Withdrawal by Subject	4
12 Weeks to 6 Months Treatment failure	1
12 Weeks to 6 Months Moved/transferred out	1
12 Weeks to 6 Months Lost to Follow-up	4
12 Weeks to 6 Months Death	1
6 Months to 18 Months Withdrawal by Subject	1
6 Months to 18 Months Treatment failure	7
6 Months to 18 Months Relapse/recurrence of TB	8
6 Months to 18 Months Moved/transferred out	6
6 Months to 18 Months Lost to Follow-up	24
6 Months to 18 Months Death	4
6 Months to 18 Months Diagnosed with multi-drug resistant tuberculosis.	1
6 Months to 18 Months Treatment stopped due to liver injury.	1
6 Months to 18 Months Still in study.	14

Baseline Characteristics

The Impact of Alcohol Consumption on Tuberculosis Treatment Outcomes

Baseline characteristics by cohort

Measure	TRUST Cohort n=303 Participants TRUST Study Cohort
Age, Continuous	37 years n=5 Participants
Sex: Female, Male Female	121 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants
Race/Ethnicity, Customized Coloured/Mixed Ancestry	284 Participants n=5 Participants
Race/Ethnicity, Customized Black African	16 Participants n=5 Participants
Race/Ethnicity, Customized Indian/Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Region of Enrollment South Africa	303 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Individuals newly diagnosed with tuberculosis and initiating treatment were classified at baseline into either Low Alcohol Use (n=102), Moderate Alcohol Use (n=133), and High Alcohol Use (n=65). 3 participants were missing data on alcohol use as their baseline PEth tests were water damaged. Therefore the overall number of participants analyzed was 300 and the respective number of participants for each of the 3 levels of alcohol use are provided as just described.

Time to sterilization/culture conversion during the first twelve weeks of treatment in patients with problem alcohol use compared to those without

Outcome measures

Measure	TRUST Cohort n=300 Participants TRUST Study Cohort
Time to Culture Conversion Low Alcohol Use	5.6 weeks Standard Deviation 2.5
Time to Culture Conversion Moderate Alcohol Use	5.4 weeks Standard Deviation 2.5
Time to Culture Conversion High Alcohol Use	5.5 weeks Standard Deviation 2.6

PRIMARY outcome

Timeframe: 4 weeks

Population: Cmax outcome measure data was collected for 104 study participants who were enrolled into Aim 2 for pharmacokinetic/pharmacodynamic analysis. This measure was collected for 4 first-line TB medications: rifampicin, isoniazid, pyrazinamide, and ethambutol.

Peak concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol in patients with problem alcohol use compared to those without

Outcome measures

Measure	TRUST Cohort n=104 Participants TRUST Study Cohort
Cmax Rifampicin	5.29 mg/L Interval 3.53 to 6.88
Cmax Isoniazid	1.63 mg/L Interval 1.25 to 2.23
Cmax Pyrazinamide	28.5 mg/L Interval 26.2 to 32.8
Cmax Ethambutol	1.98 mg/L Interval 1.75 to 2.2

PRIMARY outcome

Timeframe: 4 weeks

Population: AUC outcome measure data was collected for 104 study participants who were enrolled into Aim 2 for pharmacokinetic/pharmacodynamic analysis. This measure was collected for 4 first-line TB medications: rifampin, isoniazid, pyrazinamide, and ethambutol.

Individual patient steady state 24-hour area under curve (AUC) of isoniazid, rifampin, pyrazinamide, and ethambutol

Outcome measures

Measure	TRUST Cohort n=104 Participants TRUST Study Cohort
Area Under Curve (AUC) Rifampin	22.2 mg x h/L Interval 15.5 to 31.2
Area Under Curve (AUC) Isoniazid	6.32 mg x h/L Interval 4.53 to 13.1
Area Under Curve (AUC) Pyrazinamide	259 mg x h/L Interval 236.0 to 292.0
Area Under Curve (AUC) Ethambutol	13.2 mg x h/L Interval 11.7 to 15.1

SECONDARY outcome

Timeframe: 18 months

Population: 3 individuals were excluded from overall numbers (total N=303) because they didn't have baseline Peth collected, so there did not have alcohol use data.

Number and percent of participants that had favorable (defined as cured, treatment completed) and unfavorable (defined as treatmentfailure, death, relapse) TB outcomes. The 'other' category is defined as the treatment defaulted, was extended, participant moved or was transferred).

Outcome measures

Measure	TRUST Cohort n=300 Participants TRUST Study Cohort
Poor Treatment Outcome Favorable	246 Participants
Poor Treatment Outcome Unfavorable	24 Participants
Poor Treatment Outcome Other	19 Participants
Poor Treatment Outcome Missing	11 Participants

SECONDARY outcome

Timeframe: 6 months

Population: 3 individuals were excluded from overall numbers (total N=303) because they didn't have baseline Peth collected, so they did not have alcohol use data

Nember and percentage of patients who develop side effects to the TB drugs in patients with problem alcohol use compared to those without

Outcome measures

Measure	TRUST Cohort n=300 Participants TRUST Study Cohort
Side Effects to TB Drugs Side effects	154 Participants
Side Effects to TB Drugs No side effects	146 Participants

Adverse Events

TRUST Cohort

Serious events: 10 serious events

Other events: 0 other events

Deaths: 8 deaths

Serious adverse events

Measure	TRUST Cohort n=303 participants at risk TRUST Study Cohort
General disorders Participant death	2.6% 8/303 • Number of events 8 • 18 months
General disorders Participant coughing up blood during transport	0.33% 1/303 • Number of events 1 • 18 months
Investigations Ineligible participant enrolled	0.33% 1/303 • Number of events 1 • 18 months

Other adverse events

Adverse event data not reported

Additional Information

Karen Jacobson, MD MPH

Boston Medical Center

Phone: 617-414-5213

Email: karen.jacobson@bmc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place