Tuberculosis
Conditions
Keywords
tuberculosis, tuberculosis treatment, wirelessly observed therapy, proteus digital health, digital health feedback system
Brief summary
This study uses an ingestion sensor and a wearable sensor (worn as a patch on the skin), which are new Proteus Digital Health (PDH) 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 gives healthcare providers information about when patients have taken their TB medications. The advantage of the DHFS is that patients can take their medication where and when it is convenient for them, and do not have to wait for a nurse to directly observe them taking their medication. The purpose of this study is to find out if using these new technologies works as well as the standard method of observing in person when patients take their TB medications. This study will also look at the costs of using a DHFS for TB medications, what patients and healthcare providers think about using it, and other factors that can determine when one approach works better than another. This study has two parts. For the first part of the study (Step I), patients will have an initial screening visit and then, in one two-week period, they will have 4 study visits at the UCSD AntiViral Research Center (AVRC) and routine visits from Public Health Services (PHS) workers. This part of the study is designed to confirm that the DHFS is working correctly and is accurately collecting information about each dose of medication that patients take, and to understand what patients and healthcare providers think about using the DHFS. If patients are eligible for the second part of the study (Step II) and want to continue, that will last another 8-14 weeks with an additional 4 study visits at the AVRC. In the second part of the study, patients will be randomized into one of the following two groups. Group 1: TB treatment is monitored by continued use of the DHFS Group 2: TB treatment is monitored by the standard methods used by PHS (DOT) The second part of the study is designed to compare these two methods of observing patients taking their TB medications, what the relative costs of these methods are , and the perception by patients and/or healthcare providers of the ease of use of the novel technology.
Detailed description
PHARMACOKINETIC (PK) SUBSTUDY The purpose of the PK substudy is to prospectively evaluate the pharmacokinetic parameters of isoniazid (INH) and rifampin (RIF) concentrations derived from dosing with Rifamate when given in native format compared to over encapsulated, ingestion sensor-enabled format. The UCSD substudy aims to co-enroll 12 patients with Phase 1- the two-week investigation period of the characteristics of use of DHFS and patient acceptability. These subjects will be randomized to start on either Phase 1 or on two weeks of native Rifamate followed by 24-hour PK sampling.
Interventions
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.
OTHERSOC DOT
Sponsors
Department of Health and Human Services
Proteus Digital Health, Inc.
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Basic competency in understanding written and verbal information as it applies to DHFS use. * Persons undergoing treatment for TB that includes at least isoniazid and rifampin at the time of entry to Phase 1; of note, patients must be sputum smear negative at the time of study entry. * Laboratory values obtained by screening laboratories within 30 days of entry: * Absolute neutrophil count (ANC) \>= 1,000/mm3. * Hemoglobin \>= 9.0 g/dL. * Platelet count \>= 75,000/mm3. * AST (SGOT), ALT (SGPT), and alkaline phosphatase \<= 3 x ULN. * Total bilirubin \<= 1.5 x ULN and direct bilirubin. * Females of childbearing potential must agree to use contraception throughout the study period. * Men and women age \>= 18 years. * Eligible for anti-mycobacterial medications and in possession of prescriptions for isoniazid and rifampin, or Rifamate, as appropriate. * Willing to follow all protocol requirements. * Ability to use mobile device per investigator determination, and to wear PDH wearable sensor (i.e., no skin conditions precluding use). * Ability and willingness of subjects to give written informed consent.
Exclusion criteria
* Female who is pregnant or breast-feeding, or of childbearing potential and has a tuberculin positive test at screening and disagrees to use contraception throughout the study period. * Use of any of the prohibited medications or other non-informed medications within 30 days of study entry. * Known hypersensitivity to any of the study drugs. * Known sensitivity to skin adhesives. * Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry (Day 0). * Evidence of any anti-mycobacterial resistance, clinical or genetic, prior to study entry. Resistance testing results must be available for review by the site investigator and study protocol team prior to enrollment to ensure that no exclusionary resistance exists. * Active drug or alcohol use, or dependence, or other conditions that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Step 1: Positive Detection Accuracy (PDA) | 2 weeks | 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. |
| Step 2: Percentage of Witnessed Doses | 16 weeks | Determine the percentage of witnessed doses by DHFS and standard of care (SOC), respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize Subject Responses to Post-study Questionnaires to Collect Information Regarding Their Experience With the DHFS Using Summary Statistics. | 2-3 weeks | 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 |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| ALL 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. | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage 1 (1-3 Weeks) | Adverse Event | 1 | 0 | 0 |
| Stage 1 (1-3 Weeks) | Only participated in PK Substudy | 12 | 0 | 0 |
| Stage 1 (1-3 Weeks) | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | ALL PARTICIPANTS |
|---|---|
| Age, Continuous Stage 1 | 43 years STANDARD_DEVIATION 17 |
| Age, Continuous Stage 2 DOT | 45 years STANDARD_DEVIATION 17 |
| Age, Continuous Stage 2 WOT | 41 years STANDARD_DEVIATION 16 |
| Employment status: full-time/part time Stage 1 Full-time | 21 Participants |
| Employment status: full-time/part time Stage 1 Part-time | 8 Participants |
| Employment status: full-time/part time Stage 1 Retired | 4 Participants |
| Employment status: full-time/part time Stage 1 Unable to work (disabled) | 12 Participants |
| Employment status: full-time/part time Stage 1 Unemployed | 32 Participants |
| Employment status: full-time/part time Stage 2 DOT Full-time | 6 Participants |
| Employment status: full-time/part time Stage 2 DOT Part-time | 2 Participants |
| Employment status: full-time/part time Stage 2 DOT Retired | 1 Participants |
| Employment status: full-time/part time Stage 2 DOT Unable to work (disabled) | 4 Participants |
| Employment status: full-time/part time Stage 2 DOT Unemployed | 7 Participants |
| Employment status: full-time/part time Stage 2 WOT Full-time | 12 Participants |
| Employment status: full-time/part time Stage 2 WOT Part-time | 5 Participants |
| Employment status: full-time/part time Stage 2 WOT Retired | 0 Participants |
| Employment status: full-time/part time Stage 2 WOT Unable to work (disabled) | 6 Participants |
| Employment status: full-time/part time Stage 2 WOT Unemployed | 18 Participants |
| Ethnicity (NIH/OMB) Stage 1 Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Stage 1 Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Stage 1 Unknown or Not Reported | 3 Participants |
| Ethnicity (NIH/OMB) Stage 2 DOT Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Stage 2 DOT Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Stage 2 DOT Unknown or Not Reported | 1 Participants |
| Ethnicity (NIH/OMB) Stage 2 WOT Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Stage 2 WOT Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Stage 2 WOT Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) Stage 1 American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Stage 1 Asian | 32 Participants |
| Race (NIH/OMB) Stage 1 Black or African American | 1 Participants |
| Race (NIH/OMB) Stage 1 More than one race | 0 Participants |
| Race (NIH/OMB) Stage 1 Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Stage 1 Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) Stage 1 White | 30 Participants |
| Race (NIH/OMB) Stage 2 DOT American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Stage 2 DOT Asian | 8 Participants |
| Race (NIH/OMB) Stage 2 DOT Black or African American | 0 Participants |
| Race (NIH/OMB) Stage 2 DOT More than one race | 0 Participants |
| Race (NIH/OMB) Stage 2 DOT Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Stage 2 DOT Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) Stage 2 DOT White | 8 Participants |
| Race (NIH/OMB) Stage 2 WOT American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Stage 2 WOT Asian | 17 Participants |
| Race (NIH/OMB) Stage 2 WOT Black or African American | 0 Participants |
| Race (NIH/OMB) Stage 2 WOT More than one race | 0 Participants |
| Race (NIH/OMB) Stage 2 WOT Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Stage 2 WOT Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) Stage 2 WOT White | 14 Participants |
| Sex: Female, Male Stage 1 Female | 33 Participants |
| Sex: Female, Male Stage 1 Male | 44 Participants |
| Sex: Female, Male Stage 2 DOT Female | 8 Participants |
| Sex: Female, Male Stage 2 DOT Male | 12 Participants |
| Sex: Female, Male Stage 2 WOT Female | 20 Participants |
| Sex: Female, Male Stage 2 WOT Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 41 | 0 / 20 |
| other Total, other adverse events | 1 / 77 | 0 / 41 | 0 / 20 |
| serious Total, serious adverse events | 0 / 77 | 0 / 41 | 0 / 20 |
Outcome results
Primary
Step 1: Positive Detection Accuracy (PDA)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DHFS With IS-RM Plus SOC DOT | Step 1: Positive Detection Accuracy (PDA) | 99.3 percentage of DHFS detected doses |
Primary
Step 2: Percentage of Witnessed Doses
Determine the percentage of witnessed doses by DHFS and standard of care (SOC), respectively.
Time frame: 16 weeks
Population: Observation days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DHFS With IS-RM Plus SOC DOT | Step 2: Percentage of Witnessed Doses | 92.9 percentage of witnessed doses |
| SOC DOT | Step 2: Percentage of Witnessed Doses | 63.1 percentage of witnessed doses |
Secondary
Characterize Subject Responses to Post-study Questionnaires to Collect Information Regarding Their Experience With the DHFS Using Summary Statistics.
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
Time frame: 2-3 weeks
Population: Ease of use of the DHFS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DHFS With IS-RM Plus 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 |
| SOC DOT | Characterize Subject Responses to Post-study Questionnaires to Collect Information Regarding Their Experience With the DHFS Using Summary Statistics. | 92.8 percentage of participants |