Four-country evaluation of digital adherence technologies linked to a web-based platform to support adherence to TB treatment
| ISRCTN | ISRCTN17706019 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17706019 |
| Secondary identifying numbers | 2020-0001 |
- Submission date
- 05/11/2020
- Registration date
- 18/11/2020
- Last edited
- 18/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Tuberculosis (TB) is a bacterial infection that mainly affects the lungs. In 2017, an estimated 10 million people fell ill with TB. Not adhering to treatment leads to unfavourable outcomes, relapse, drug resistance, disease transmission and increased health system costs. Innovations are therefore needed to improve TB treatment adherence. Digital adherence technologies (DAT) may be a major step forward. The aim of this study is to measure the impact of DATs for daily monitoring of adherence for adult TB patients in the Philippines, Tanzania, South Africa and Ukraine.
Who can participate?
All adults (according to country definition) receiving treatment for TB in participating health facilities.
What does the study involve?
Facilities in each country will be randomly allocated to employ either a DAT intervention or the standard of care. At intervention facilities, health care providers will enrol patients receiving treatment for drug-sensitive TB who are willing to use the DATs. Patients who decline will be offered the standard of care. Over the course of the participant’s treatment at these facilities, TB healthcare providers will monitor a patient's adherence pattern generated from the DAT using a web-based platform. This will enable daily monitoring and give healthcare providers the ability to provide a tailored response to those patients requiring more treatment support, including the use of messaging and reminders supported by the platform and possibly home visits. The study will evaluate the treatment outcome of patients, comparing the intervention facilities to standard of care facilities. In addition, several sub-studies will assess how the intervention may work in patients receiving treatment for both drug-sensitive and drug-resistant-TB.
What are the possible benefits and risks of participating?
By participating patients who need it may receive more support to complete their treatment for TB as intended while allowing patients demonstrating good adherence, greater autonomy and freedom to self-manage their own care. This may include a decrease in the burden of visits to the health facility compared to those receiving the standard of care. This may benefit both those on TB treatment as well as their healthcare providers. Possible risks to participants include inadvertent disclosure of TB status, and possibly inferred HIV status in some settings by use or possession of tools (smart pill boxes or medication sleeves) associated with TB.
Where is the study run from?
KNCV Tuberculosis Foundation (Netherlands) with support from the London School of Hygiene and Tropical Medicine (UK)
When is the study starting and how long is it expected to run for?
November 2020 to December 2022
Who is funding the study?
Unitaid (Switzerland)
Who is the main contact?
Degu Jerene Dare, MD, PhD, MBA
degu.dare@kncvtbc.org
Contact information
Public, Scientific
86
Maanweg 174
's-Gravenhage
2516 AB
Netherlands
 ORCID ID |
0000-0001-7853-4211 |
|---|---|
| Phone | +31 (0)682102074 |
| degu.dare@kncvtbc.org |
Study information
| Study design | Multicountry multicenter interventional open health-facility-based cluster randomized trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Cluster randomised trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Adherence Support Coalition to End TB (ASCENT): four-country evaluation of digital adherence technologies for TB treatment |
| Study acronym | ASCENT |
| Study hypothesis | It is hypothesized that implementing digital adherence technologies (DATs) with daily monitoring using a web-based platform and a differentiated response to patient adherence among adult patients receiving drug-sensitive TB therapy will decrease poor end of treatment outcomes relative to the standard of care. |
| Ethics approval(s) | 1. South Africa: Approved 23/04/2020, University of Witwatersand (Johannesburg Secretariate, Suite 189 Private bag x2600, Houghton 20141, South Africa +27 (0)11 274 9200; email: not available), ref 2001102 2. Ukraine: Approved 04/09/2020, Public Health Center MoH of Ukraine (41 Yaroslavska Street, Kyiv, 04071, Ukraine; tel: not available; irb@phc.org.ua), ref IRB2019-33 3. Tanzania: Approved 10/06/2020, The United Republic of Tanzania (3 Barack Obama Drive, PO Box 9653, 11101 Dar es Salaam, Tanzania; +255 (0)22 2121400; nimrethics@gmail.com), ref NIMR/HQ/R.8a/Vol. IX/3431 4. Philippines: Approved 03/07/2020, Republic of the Philippines Department of Health Single Joint Research Ethics Board (contact details not available), ref: SJREB-2019-57 |
| Condition | Tuberculosis |
| Intervention | Randomization of the clusters, health facilities or rayons (in Ukraine), to the intervention arm or the standard of care arm in a ratio of 1:1, will be conducted using stratification and restriction in order to reduce the intra-cluster correlation (former) and help ensure a balance between study arms. One row of a sample frame of 10,000 randomly selected possible allocations of facilities/rayons to the treatment or control arms after restriction will be randomly selected by an NTP official. In facilities randomized to the intervention, TB medication adherence monitoring will be done using digital adherence technologies (DATs) linked to a web-based adherence monitoring platform. Control facilities will use adherence monitoring employing the standard of care. In facilities randomized to the intervention, TB medication adherence monitoring will be done using digital adherence technologies (DATs) - either 99DOTS medication sleeves or Evrimed smart pill boxes - linked to a web-based adherence monitoring platform. Control facilities will use adherence monitoring employing the standard of care. In three countries intervention facilities will themselves be randomized to receive either the 99DOTS or smart pill box. In Ukraine, only the smart pill boxes will be employed. Facilities in each country will be randomized to employ either a DAT intervention or the standard of care in a ratio of one to one. At intervention facilities, health care providers will enroll patients receiving treatment for drug-sensitive TB who are willing to consent to use the DATs. Patients who decline will be offered the standard of care. Over the course of the participant’s treatment at these facilities, TB health care providers will use a single user interface on tablets to view a patient's adherence pattern generated from the DAT via a web-based platform. This will enable daily monitoring and give healthcare providers the ability to provide a step-wise differentiated response to those patients requiring more treatment support, including the use of messaging and reminders supported by the platform and possibly home visits. The particular differentiated care algorithm in each country will be worked out during the study preparatory phase. The intervention will be employed over the course of their participant’s treatment at these facilities (approximately 6 months). The follow-up is limited to the duration of their treatment. The study will evaluate the treatment outcome of patients, comparing that in the intervention facilities relative to the standard of care facilities in an intent-to-treat analysis. In addition, several sub-studies will include process evaluation components in order to provide an understanding of how the intervention may work in patients receiving treatment for both drug-sensitive and drug-resistant-TB. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 99DOTS medication sleeves, Evrimed smart pill boxes |
| Primary outcome measure | The proportion of adult DS-TB patients with poor end of treatment outcome, defined as having documented treatment failure, lost to follow-up or death as reported in the facility/rayon TB register upon completion of treatment (approximately 6 months) |
| Secondary outcome measures | 1. The proportion of adult DS-TB patients who are lost to follow-up during treatment as reported in the facility/rayon TB register 6 months after the initiation of therapy 2. Time to treatment completion among DS-TB patients calculated from start and completion date as reported in the facility/rayon TB register upon completion of therapy 3. The proportion of adult DS-TB patients with poor treatment outcomes, as reported in the facility/rayon TB register upon completion of therapy Intervention arm only: 4. Patterns of longitudinal technology engagement in the intensive and continuation phase, to be characterized, at a minimum, as the proportion of days upon completion of a patients treatment phase (intensive and continuation) with a dose being reported (adherence) to the platform 5. The proportion of patient events upon completion of treatment who had a differentiated response (either reminder SMS, home visit or facility visits) due to non-adherence as reported on the platform, among all patients and among non-adherent patients 6. The proportion of patients who received phone calls, home visits, and motivational counselling due to a non-adherence event as reported on the platform over the course of a patients treatment Impact modelling: 7. The change in the number of adult DS-TB patients with poor treatment outcome at the time of treatment completion compared to the current standard of care if the intervention were to be scaled up nationally, projected using simple cohort model using study data 8. The cost-effectiveness of DAT compared to standard of care from health system and societal perspectives, relative to country-specific cost-effectiveness thresholds DR-TB patients: 9. Patterns of longitudinal technology engagement in the intensive and continuation phase to be characterized, at the minimum, as the proportion of days through the end of treatment with a dose being reported (adherence) to the platform 10. The proportion of adult DR-TB patients with poor treatment outcomes as reported in the facility/rayon TB register at the interim (6 months) or completion of DR-TB treatment |
| Overall study start date | 04/11/2020 |
| Overall study end date | 31/12/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Tanzania: 72 facility and 8,136 patients; South Africa: 58 facilities and 14,674 patients; Philippines: 62 facilities and 21,700 patients; Ukraine: 11 facilities and 1936 patients |
| Total final enrolment | 25606 |
| Participant inclusion criteria | Adult (based on country) pulmonary DS-TB patients initiated on TB treatment |
| Participant exclusion criteria | Does not meet inclusion criteria |
| Recruitment start date | 01/01/2021 |
| Recruitment end date | 30/06/2022 |
Locations
Countries of recruitment
- Philippines
- South Africa
- Tanzania
- Ukraine
Study participating centres
Kyiv
04071
Ukraine
Donetska Oblast
84333
Ukraine
Mykolaivska oblast
57130
Ukraine
Lviv, Lvivska oblast
79000
Ukraine
Odesa, Odeska oblast
65014
Ukraine
Uzhhorod, Zakarpatska oblast
88000
Ukraine
Malolas City, Bulacan
3000
Philippines
San Fernando, Pampanga
2000
Philippines
Mwanza
-
Tanzania
Geita
-
Tanzania
Arusha
-
Tanzania
Manyara
-
Tanzania
Johannesburg
2001
South Africa
Cape Town
8000
South Africa
Sponsor information
Research organisation
86 Maanweg 174
's-Gravenhage
2516 AB
Netherlands
| Phone | +31 (0)682102074 |
|---|---|
| jens.levy@kncvtbc.org | |
| Website | https://www.kncvtbc.org/ |
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 01/01/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | The protocol will be made available on ASCENT website (https://www.digitaladherence.org/) from 15/11/2020 onwards. The research findings will be presented first to national stakeholders, and disseminated to the Community Advisory Board, stakeholders and participants in each country by means of local meetings, and presented at national and international conferences. The results will be written as country-specific articles for submission to suitable scientific journals. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a publicly available repository. The researchers will provide a participant level (de-identified and anonymized) dataset on OpenTrials (https://explorer.opentrials.net/) sufficient to reproduce analysis upon publication of the principal findings related to the primary objective. Consent from participants is available for the adherence data only. Outcome data will be available for those patients who did not opt-out. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 14/03/2023 | 15/03/2023 | Yes | No | |
| Other publications | A cross-sectional survey among adults with drug-sensitive tuberculosis (DS-TB), participating in pragmatic cluster-randomized trials, including this study | 20/02/2024 | 11/03/2024 | Yes | No |
| Results article | Adherence | 11/03/2025 | 18/03/2025 | Yes | No |
Editorial Notes
18/03/2025: Publication reference and total final enrolment added.
11/03/2024: Publication reference added.
05/03/2024: The study contact was updated.
15/03/2023: Publication reference added.
12/11/2020: Trial's existence confirmed by the WHO Research Ethics Review Committee.
