Trial Outcomes & Findings for Wirelessly Observed Therapy in Comparison to Directly Observed Therapy for the Treatment of Tuberculosis (NCT NCT01960257)

NCT ID: NCT01960257

Last Updated: 2021-05-12

Results Overview

Determine positive detection accuracy (PDA, direct confirmation of TB medication ingestion) of the DHFS when compared to a healthcare worker witnessing actual TB medication ingestion.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 92 participants
• Primary outcome timeframe: 2 weeks
• Results posted on: 2021-05-12

Participant Flow

In Stage 1, 92 participants screened, 77 were enrolled in WOT+ SOC DOT. Excluded from stage 2, n=16: 12 only participated in PK substudy, 3 withdrew consent and 1 withdrew due to AE. Stage 2, 61 participants enrolled and were divided into 2 arms, 41 in WOT, and 20 in DOT.

Participant milestones

Measure	WOT+ SOC DOT Digital Health Feedback System (DHFS) Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) co-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. Digital Health Feedback System: This intervention uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new technologies approved by the FDA, to collect information about patients taking their TB medications. The wearable sensor records information, which is uploaded wirelessly to a mobile device and then to a secure computer. Together the sensors and the mobile device transmitting the information to the study computer are called a digital health feedback system (DHFS), which provides information about when patients have taken their TB medications.	Wirelessly Observed Therapy (WOT) IS-Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) co-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment.	Directly Observed Therapy (DOT) Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Stage 1 (1-3 Weeks) STARTED	77	0	0
Stage 1 (1-3 Weeks) COMPLETED	61	0	0
Stage 1 (1-3 Weeks) NOT COMPLETED	16	0	0
Stage 2(1-4 Months, Not to Exceed 12wks) STARTED	0	41	20
Stage 2(1-4 Months, Not to Exceed 12wks) COMPLETED	0	41	20
Stage 2(1-4 Months, Not to Exceed 12wks) NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	WOT+ SOC DOT Digital Health Feedback System (DHFS) Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) co-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. Digital Health Feedback System: This intervention uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new technologies approved by the FDA, to collect information about patients taking their TB medications. The wearable sensor records information, which is uploaded wirelessly to a mobile device and then to a secure computer. Together the sensors and the mobile device transmitting the information to the study computer are called a digital health feedback system (DHFS), which provides information about when patients have taken their TB medications.	Wirelessly Observed Therapy (WOT) IS-Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) co-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment.	Directly Observed Therapy (DOT) Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Stage 1 (1-3 Weeks) Only participated in PK Substudy	12	0	0
Stage 1 (1-3 Weeks) Withdrawal by Subject	3	0	0
Stage 1 (1-3 Weeks) Adverse Event	1	0	0

Baseline Characteristics

Each row represents data collected for a particular group based on treatment assignment.

Baseline characteristics by cohort

Measure	ALL PARTICIPANTS n=77 Participants Digital Health Feedback System (DHFS) Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) co-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT Digital Health Feedback System: This intervention uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new technologies approved by the FDA, to collect information about patients taking their TB medications. The wearable sensor records information, which is uploaded wirelessly to a mobile device and then to a secure computer. Together the sensors and the mobile device transmitting the information to the study computer are called a digital health feedback system (DHFS), which provides information about when patients have taken their TB medications.
Age, Continuous Stage 1	43 years STANDARD_DEVIATION 17 • n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Age, Continuous Stage 2 WOT	41 years STANDARD_DEVIATION 16 • n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Age, Continuous Stage 2 DOT	45 years STANDARD_DEVIATION 17 • n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 1 · Female	33 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 1 · Male	44 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 2 WOT · Female	20 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 2 WOT · Male	21 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 2 DOT · Female	8 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Sex: Female, Male Stage 2 DOT · Male	12 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 1 · Hispanic or Latino	38 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 1 · Not Hispanic or Latino	36 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 1 · Unknown or Not Reported	3 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 WOT · Hispanic or Latino	21 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 WOT · Not Hispanic or Latino	18 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 WOT · Unknown or Not Reported	2 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 DOT · Hispanic or Latino	11 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 DOT · Not Hispanic or Latino	8 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Ethnicity (NIH/OMB) Stage 2 DOT · Unknown or Not Reported	1 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · American Indian or Alaska Native	0 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · Asian	32 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · Native Hawaiian or Other Pacific Islander	1 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · Black or African American	1 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · White	30 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · More than one race	0 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 1 · Unknown or Not Reported	13 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · American Indian or Alaska Native	0 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · Asian	17 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · Native Hawaiian or Other Pacific Islander	1 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · Black or African American	0 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · White	14 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · More than one race	0 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 WOT · Unknown or Not Reported	9 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · American Indian or Alaska Native	0 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · Asian	8 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · Black or African American	0 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · White	8 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · More than one race	0 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Race (NIH/OMB) Stage 2 DOT · Unknown or Not Reported	4 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 1 · Full-time	21 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 1 · Part-time	8 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 1 · Unemployed	32 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 1 · Retired	4 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 1 · Unable to work (disabled)	12 Participants n=77 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 WOT · Full-time	12 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 WOT · Part-time	5 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 WOT · Unemployed	18 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 WOT · Retired	0 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 WOT · Unable to work (disabled)	6 Participants n=41 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 DOT · Full-time	6 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 DOT · Part-time	2 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 DOT · Unemployed	7 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 DOT · Retired	1 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.
Employment status: full-time/part time Stage 2 DOT · Unable to work (disabled)	4 Participants n=20 Participants • Each row represents data collected for a particular group based on treatment assignment.

PRIMARY outcome

Timeframe: 2 weeks

Population: Positive Detection Accuracy (PDA): PDA is defined as DHFS detection of the ingestion of a dose of IS-RM when compared to a witnessed ingestion of the same dose of medication.

Determine positive detection accuracy (PDA, direct confirmation of TB medication ingestion) of the DHFS when compared to a healthcare worker witnessing actual TB medication ingestion.

Outcome measures

Measure	DHFS With IS-RM Plus SOC DOT n=77 Participants Initially all participants (n=77) received DHFS IS-RM in conjunction with witnessed medication doses (DOT) for 2-3 weeks to allow calculation of DHFS IS-RM PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples.	SOC DOT Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Step 1: Positive Detection Accuracy (PDA)	99.3 percentage of DHFS detected doses Interval 98.1 to 100.0	—

PRIMARY outcome

Timeframe: 16 weeks

Population: Observation days

Determine the percentage of witnessed doses by DHFS and standard of care (SOC), respectively.

Outcome measures

Measure	DHFS With IS-RM Plus SOC DOT n=93 Days Initially all participants (n=77) received DHFS IS-RM in conjunction with witnessed medication doses (DOT) for 2-3 weeks to allow calculation of DHFS IS-RM PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples.	SOC DOT n=101 Days Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Step 2: Percentage of Witnessed Doses	92.9 percentage of witnessed doses Interval 89.0 to 96.0	63.1 percentage of witnessed doses Interval 58.0 to 67.0

SECONDARY outcome

Timeframe: 2-3 weeks

Population: Ease of use of the DHFS

Subject responses regarding satisfaction with the DHFS were reported on post study questionnaires regarding their experience with the DHFS and the usability of the system, using summary statistics. Areas evaluated may include ease of use, time needed to use the system, negative impressions, and changes to quality of life. Analyses of individual questions as well as summary metrics across questions were explored.

Percentage of participants who reported being comfortable replacing the patch on their own

Outcome measures

Measure	DHFS With IS-RM Plus SOC DOT n=71 Participants Initially all participants (n=77) received DHFS IS-RM in conjunction with witnessed medication doses (DOT) for 2-3 weeks to allow calculation of DHFS IS-RM PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples.	SOC DOT n=41 Participants Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Characterize Subject Responses to Post-study Questionnaires to Collect Information Regarding Their Experience With the DHFS Using Summary Statistics.	75.3 percentage of participants	92.8 percentage of participants

Adverse Events

WOT+ SOC DOT

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Wirelessly Observed Therapy (WOT)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Directly Observed Therapy (DOT)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	WOT+ SOC DOT n=77 participants at risk Digital Health Feedback System (DHFS) Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) over-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. Digital Health Feedback System: This intervention uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new technologies approved by the FDA, to collect information about patients taking their TB medications. The wearable sensor records information, which is uploaded wirelessly to a mobile device and then to a secure computer. Together the sensors and the mobile device transmitting the information to the study computer are called a digital health feedback system (DHFS), which provides information about when patients have taken their TB medications.	Wirelessly Observed Therapy (WOT) n=41 participants at risk IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate) over-encapsulated with ingestion sensor - 2 capsules orally daily (QD) administered orally preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. Digital Health Feedback System: This intervention uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new technologies approved by the FDA, to collect information about patients taking their TB medications. The wearable sensor records information, which is uploaded wirelessly to a mobile device and then to a secure computer. Together the sensors and the mobile device transmitting the information to the study computer are called a digital health feedback system (DHFS), which provides information about when patients have taken their TB medications.	Directly Observed Therapy (DOT) n=20 participants at risk Isoniazid 300 mg -1 tablet orally QD plus rifampin 300 mg - 2 capsules orally QD, OR Rifamate (combination of isoniazid 150 mg and rifampin 300 mg) - 2 capsules orally QD preferably on an empty stomach first thing in the morning for 10-16 weeks, depending on time left to complete TB treatment. SOC DOT
Skin and subcutaneous tissue disorders Pruritus at patch site	1.3% 1/77 • Number of events 1 • Adverse events were assessed for 2 weeks in Stage 1 and up to 12 months in Stage 2, Through study completion, an average of 12 months, or similar.	0.00% 0/41 • Adverse events were assessed for 2 weeks in Stage 1 and up to 12 months in Stage 2, Through study completion, an average of 12 months, or similar.	0.00% 0/20 • Adverse events were assessed for 2 weeks in Stage 1 and up to 12 months in Stage 2, Through study completion, an average of 12 months, or similar.

Additional Information

Dr. Sara H. Browne

University of California, San Diego

Phone: 619 543 8080

Email: shbrowne@health.ucsd.edu

Results disclosure agreements

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