Clinical trial NCT03800888: Real-time Tuberculosis Medication Adherence Intervention in Rural Southwestern Uganda
Official title: Real-time Tuberculosis Medication Adherence Intervention in Rural Southwestern Uganda
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Tuberculosis
Keywords: Real-time
Medication Adherence
Tuberculosis
Lead sponsor: Mbarara University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: National Institutes of Health (NIH)
First posted: 2019-01-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized using the 1:1:1 allocation ratio to the following arms: 1) Fixed and linked SMS reminders, 2) SMS notifications to social supporters, and 3) no SMS (control). All participants will have adherence monitored in real-time for 6 months.
Primary purpose: SUPPORTIVE_CARE

Brief summary: With an estimated 60,000 people diagnosed with TB (Tuberculosis) annually, Uganda holds the 16th position of the 22 countries with highest cases of TB in the world. The Uganda national target of utilizing the DOTS (Direct Observed Treatment Short Course) to successfully treat 85% of patients diagnosed with TB has not been met. Currently, the country only detects 49.6% TB case detection, of which it successfully treats 73%. The DOTS strategy has suffered many socioeconomic challenges, which have resulted into its abandonment by many of the Ugandan hospitals. Poor TB medication adherence greatly attribute to the many cases of TB in Uganda. Causes of non-adherence to TB medication include lack of patient follow-up, patients' lack of transport to go to the clinics to pick up drugs, patients' forgetfulness. There is evidence that real time adherence monitoring linked with SMS reminders and social support notifications can address barriers to sustained ART (antiretroviral therapy) adherence. Such novel interventions addressing TB medication adherence challenges in low resource settings to date are limited. The prevailing SMS-based studies for TB medication adherence report mixed results, do not strategically link interventions with missed doses, and have largely been implemented in developed countries. To date, little is known about the use of real-time adherence monitoring technologies for TB medication adherence in resource-limited settings.

The goal of this research is to investigate the use of real time adherence monitoring technology linked with SMS reminders and notifications for TB medication adherence in rural southwestern Uganda.

The investigator will develop and quantitatively test a real-time adherence monitoring intervention with 60 individuals initiating TB treatment, and 40 social supporters. The investigator will randomize participants (1:1:1) to the following arms: 1) Fixed and linked SMS reminders, 2) SMS notifications to social supporters, and 3) no SMS (control). All participants will have adherence monitored in real-time for 6 months.

Detailed description: This study has three major aims (Aims 1, 2 and 3)

Aim 1: Carry out a formative qualitative study to assess barriers and facilitators to TB medication adherence, and identify optimal SMS reminders, notifications, and initial feasibility of real time adherence monitoring. 35 TB patients will be recruited from the TB clinic in Mbarara Regional Referral Hospital (MRRH), and up to 15 social supporters specified by the TB patients (one per TB patient). Drawing from technology adoption and behavioral change models, the investigator will use semi-structured interviews to assess the initial feasibility and acceptability of the intervention, as well the barriers and facilitators to TB medication adherence, and how they can be addressed using the proposed intervention. The purpose will be to inform the development the technology necessary to conduct a real-time intervention involving a wireless monitor and SMS reminders and notifications (Aim 2 and 3).

Aim 2: Develop a TB medication adherence intervention based on SMS reminders (fixed and/or linked to real-time detection of missed doses) and assess its acceptability, feasibility and preliminary impact on adherence.

The Investigators will use real-time electronic adherence monitoring (i.e., Wisepill) to follow 60 TB-infected individuals initiating TB treatment in Mbarara Regional Referral Hospital (MRRH) for six months. Using a 1:1:1 manner, participants will be randomized to one of the following three study arms (details of each intervention will be informed by the data collected in Aim 1):

1. Intervention Arm A: SMS reminders on a fixed schedule
2. Intervention Arm B: SMS reminders linked to missed doses
3. Control: No SMS reminders.

Qualitative interviews to understand the patients experiences with Wisepill adherence monitoring and the SMS reminders will be carried out, depending on the study arm to which they are assigned. The first set of interviews for Arms A and B will be conducted at the end of Month 3 of the study. The second set of interviews is planned to be conducted within two weeks after the first 24+ hour lapse in Wisepill signal for the participants in the intervention arms (A and B). If there is no 24+ hour lapse, the interview will take place at the end of the study. The control participants in Arm C's interview will occur at a convenient time during Months 3-6. The effect sizes will be estimated by comparing adherence at the end of six months between each intervention group and the control group. The primary outcome will be percent adherence.

Treatment outcomes will be defined according to WHO definitions, where cure and completed treatment are defined as successful treatment outcomes (WHO 2014). Unsuccessful treatment outcomes for active TB treatment will include death ascertained from hospital death registry, treatment failure (sputum smear positive at 6 months) and loss to follow-up. Treatment outcomes will be compared for both intervention and control arms.

Aim 3: Develop a social support intervention linked to real-time adherence monitoring and assess its acceptability, feasibility and preliminary impact on adherence. Members of pre-existing social support networks for the same 40 TB-infected individuals in the two intervention arms described in Aim 2 above will be recruited to receive real-time SMS notification of sustained non-adherence (i.e., gaps of \>24 hours) over the latter four months of follow-up. The investigators will continue to follow the 20 TB-infected individuals in the control group (i.e., electronic monitoring alone) to estimate the effect size of the intervention on adherence at the end of the six-month period. Qualitative interviews to understand the experiences of participants in each study arm and the social supporters with special emphasis on understanding mechanisms of effects of the SMS reminders, forms and dynamics of support, experiences with the SMS reminders/notifications, and technical problems encountered will be conducted. The results of Aim 3 will be used to determine the types of SMS (fixed versus linked SMS), and the nature of social support that shows the most promise for real time intervention on anti-TB medication adherence and cure.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria for Wisepill participants:

* Newly diagnosed with TB per the clinic records
* Starting TB treatment now or within the next two weeks
* Age 18 years and older
* Live in the Mbarara District (20 km from MRRH)
* Own a cell phone for personal use and have reliable cellular phone reception at home on networks (MTN or Airtel) supported by the technology used in this study
* Know how to use SMS
* Willing and able to give consent
* Willing and able to name one or two social supporters who are able to use SMS and have cellular phones using network provider (MTN or Airtel) supported by the technology used in this study.

Exclusion Criteria for Wisepill Participants:

* Unable to use SMS (The investigators will train and test this skill at recruitment)
* Unwilling to receive SMS reminder
* Severe mental condition limiting the ability to provide consent
* Cellular phone reception is not reliable

Inclusion Criteria for Social Supporters

* Know a Wisepill participant and be aware s/he has TB
* Have provided help to that Wisepill participant at least once, i.e,

  * Helping him/her get to clinic by loaning or giving money, driving the patient , or taking care of his/her job or children while he/she is away
  * Helping the patient take medicines through encouragement or reminders
  * Motivating the patient to take medicines, including addressing cognitive and behavioral barriers such as depression and alcohol use
* Age 18 years or older
* Live in Mbarara District (within 20 KM from MRRH)
* Willing and able to provide consent.

Exclusion:

* Unable to use SMS (Investigators will train and test this skill at recruitment)
* Unwilling to receive SMS reminder
* Severe mental condition limiting the ability to provide consent
* Cellular phone reception is not reliable

Primary outcomes:
measure: Percent adherence
timeFrame: 12 Weeks
Secondary outcomes:
measure: Treatment success rate.
timeFrame: 24 Weeks
Other outcomes:
Locations:
city: Mbarara
country: Uganda
facility: Mbarara Regional Referral Hospital
Study officials:
References:
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