Trial Outcomes & Findings for Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System (NCT NCT02797262)
NCT ID: NCT02797262
Last Updated: 2021-12-20
Results Overview
Adherence to antiretroviral therapy (ART) measured by Proteus digital health feedback (PDHF) system for 16 weeks, including percent of prescribed medication taken.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
130 participants
Primary outcome timeframe
Adherence to ART measured by PDHF system for 16 weeks
Results posted on
2021-12-20
Participant Flow
Participant milestones
| Measure |
Intervention
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
Usual care (UC) is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
65
|
|
Overall Study
Baseline
|
54
|
58
|
|
Overall Study
COMPLETED
|
45
|
54
|
|
Overall Study
NOT COMPLETED
|
20
|
11
|
Reasons for withdrawal
| Measure |
Intervention
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
Usual care (UC) is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
|
Overall Study
Lost to Follow-up
|
10
|
7
|
|
Overall Study
Death
|
1
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
COVID-19
|
2
|
1
|
|
Overall Study
Out-of-country
|
1
|
0
|
Baseline Characteristics
Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System
Baseline characteristics by cohort
| Measure |
Intervention
n=54 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=58 Participants
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
53 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Continuous
|
46.7 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
45.7 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
46.2 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex/Gender, Customized
Gender · Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Gender · Male
|
44 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Gender · Transgender: Male to Female
|
5 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race and Ethnicity · White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race and Ethnicity · Black
|
24 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race and Ethnicity · Latino
|
19 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race and Ethnicity · Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race and Ethnicity · Other
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Education
8th grade or less/ Some high school but did not graduate
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Education
High school graduate/ Some college but no degree
|
38 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Education
Completed college/ More than four-year college degree
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Employment
Part-time/full-time
|
9 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Employment
None/full-time student/retired/disabled
|
45 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
HIV+ Years
|
14.5 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
14.0 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
14.2 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Years under Antiretroviral Treatment
|
12.6 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
11.6 years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
12.0 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
History of AIDS Diagnosis
Yes
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
History of AIDS Diagnosis
No
|
42 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Detectable Viral Load at Baseline
Less than 50 copies/mL
|
35 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Detectable Viral Load at Baseline
Greater than 50 copies/mL
|
19 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Adherence to ART measured by PDHF system for 16 weeksAdherence to antiretroviral therapy (ART) measured by Proteus digital health feedback (PDHF) system for 16 weeks, including percent of prescribed medication taken.
Outcome measures
| Measure |
Intervention
n=54 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Adherence Measured by Sensor by Percentage of Prescribed Medications Taken
|
87.5 percentage of prescribed medication
Standard Deviation 33.1
|
—
|
PRIMARY outcome
Timeframe: Blood samples will be obtained in all participants before and 2 and 6 hours following an observed dose (baseline) and then at weeks 4, 8, 12, 16, 20, 24 and 28.Population: For the trial phase, we pick the most common drug with the longest plasma half-life to use for the PK-based method of adherence. That ended up being tenofovir alafenamide (TAF). Only 86 of the participants in the final analysis had available data for the PK analysis.
The plasma concentration-time data of tenofovir (TFV) from participants who have a tenofovir alafenamide (TAF) in their regimen are used to quantify intra-patient pharmacokinetic (PK) variability as a measure of adherence. Plasma concentrations of TFV are measured by liquid chromatography/tandem mass spectrometry. A population PK model will be developed using a nonlinear mixed-effects approach with data from all the time points. The integrated PK adherence score (IPAM) will be calculated. The IPAM score ranges from 0 to 1. A high score indicates high concentration predictability and relatively higher adherence, while a low score indicates low predictability and lower adherence.
Outcome measures
| Measure |
Intervention
n=44 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=42 Participants
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Pharmacokinetic Adherence by Integrated Pharmacokinetic Adherence Score
|
0.817 score on a scale
Standard Deviation 0.276
|
0.798 score on a scale
Standard Deviation 0.267
|
PRIMARY outcome
Timeframe: Self-report adherence will be measured at baseline, and weeks 4, 8, 12, 16, 20, 24, and 28.Population: Lost to follow-up, missed visits, or no self-reported adherence.
The investigators will use a widely-used measure of self-reported adherence for percent of prescribed dose taken during the preceding seven days. This tool is easy to use and has been significantly associated with virological and immunological outcomes. Due to its potential bias, self-reported adherence will be calibrated by drug level concentration to leverage its accuracy and used in analysis when calibrated self-report adherence is appropriate to be used.
Outcome measures
| Measure |
Intervention
n=54 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=58 Participants
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 0
|
90.7 percentage of prescribed medication
Standard Deviation 14.5
|
87.4 percentage of prescribed medication
Standard Deviation 13.2
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 4
|
91.1 percentage of prescribed medication
Standard Deviation 15.7
|
87.4 percentage of prescribed medication
Standard Deviation 15.2
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 8
|
90.6 percentage of prescribed medication
Standard Deviation 17.0
|
91.6 percentage of prescribed medication
Standard Deviation 13.5
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 12
|
88.3 percentage of prescribed medication
Standard Deviation 17.0
|
82.1 percentage of prescribed medication
Standard Deviation 24.9
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 16
|
88.7 percentage of prescribed medication
Standard Deviation 17.5
|
91.7 percentage of prescribed medication
Standard Deviation 16.3
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 20
|
90.7 percentage of prescribed medication
Standard Deviation 20.9
|
84.5 percentage of prescribed medication
Standard Deviation 23.2
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 24
|
94.8 percentage of prescribed medication
Standard Deviation 8.8
|
87.3 percentage of prescribed medication
Standard Deviation 22.4
|
|
Self-Reported Medication Adherence and "Change" Over Time
Week 28
|
93.0 percentage of prescribed medication
Standard Deviation 11.8
|
90.1 percentage of prescribed medication
Standard Deviation 19.8
|
SECONDARY outcome
Timeframe: Baseline, weeks 4, 8, 12, 16, and 28.Population: Lost to follow-up, missed visits, or failed to draw blood viral load.
Viral Load will be measured at baseline, weeks 4, 8, 12, 16, and 28.
Outcome measures
| Measure |
Intervention
n=54 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=58 Participants
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Viral Load
Week 0
|
2.273 log10 copies/mL
Standard Deviation 1.158
|
2.061 log10 copies/mL
Standard Deviation 0.954
|
|
Viral Load
Week 4
|
1.916 log10 copies/mL
Standard Deviation 0.793
|
1.906 log10 copies/mL
Standard Deviation 0.516
|
|
Viral Load
Week 8
|
1.851 log10 copies/mL
Standard Deviation 0.680
|
1.916 log10 copies/mL
Standard Deviation 0.711
|
|
Viral Load
Week 12
|
1.873 log10 copies/mL
Standard Deviation 0.653
|
1.937 log10 copies/mL
Standard Deviation 0.671
|
|
Viral Load
Week 16
|
1.895 log10 copies/mL
Standard Deviation 0.691
|
1.988 log10 copies/mL
Standard Deviation 0.895
|
|
Viral Load
Week 28
|
1.957 log10 copies/mL
Standard Deviation 0.816
|
2.230 log10 copies/mL
Standard Deviation 1.117
|
SECONDARY outcome
Timeframe: on: CD4 will be measured at baseline, weeks 4, 8, 12, 16, and 28.Population: Lost to follow-up, missed visits, or failed to draw blood CD4.
CD4 cell count is a test that measures the number of CD4 cells (a type of the human T-lymphocyte cells) in a HIV patient's blood. The absolute CD4 cell count is measured by a simple blood test, the results of which are reported as the number of CD4 cells per cubic millimeter of blood. HIV-negative people typically have absolute CD4 cell counts between 600 and 1200 cells per cubic millimeter. HIV is a fatal infection, characterized by the targeting and destruction of CD4 cells. People with advanced HIV can have 200 or fewer CD4 cells per cubic millimeter.
Outcome measures
| Measure |
Intervention
n=54 Participants
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=58 Participants
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Cluster of Differentiation 4 (CD4)
Week 0
|
526.17 cells/cubic millimeters
Standard Deviation 279.10
|
542.78 cells/cubic millimeters
Standard Deviation 279.31
|
|
Cluster of Differentiation 4 (CD4)
Week 4
|
531.02 cells/cubic millimeters
Standard Deviation 273.85
|
553.08 cells/cubic millimeters
Standard Deviation 271.42
|
|
Cluster of Differentiation 4 (CD4)
Week 8
|
522.00 cells/cubic millimeters
Standard Deviation 280.32
|
582.25 cells/cubic millimeters
Standard Deviation 293.29
|
|
Cluster of Differentiation 4 (CD4)
Week 12
|
501.20 cells/cubic millimeters
Standard Deviation 251.46
|
577.20 cells/cubic millimeters
Standard Deviation 295.79
|
|
Cluster of Differentiation 4 (CD4)
Week 16
|
522.91 cells/cubic millimeters
Standard Deviation 273.61
|
562.96 cells/cubic millimeters
Standard Deviation 314.09
|
|
Cluster of Differentiation 4 (CD4)
Week 28
|
538.80 cells/cubic millimeters
Standard Deviation 301.42
|
587.69 cells/cubic millimeters
Standard Deviation 318.24
|
Adverse Events
Intervention
Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths
Control
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intervention
n=57 participants at risk
Building on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Proteus digital health feedback (PDHF) system: Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).
|
Control
n=58 participants at risk
UC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
1.8%
1/57 • 28 weeks
|
0.00%
0/58 • 28 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place