Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR201902681157721 Date of Approval: 11/02/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title TB MONITORING ADHERENCE AND TREATMENT ENDPOINTS PROJECT:
Official scientific title TB MONITORING ADHERENCE AND TREATMENT ENDPOINTS PROJECT: The use of medication monitors and a differentiated care approach to improve TB adherence
Brief summary describing the background and objectives of the trial Background: South Africa, the country with the highest TB incidence (781/100,000 population), reported treatment success rates of 81% among new and retreatment patients, 80% among HIV-positive TB patients and 54% among patients with rifampicin resistance. A South African TB Consortium was recently established to test innovations to reduce gaps in the TB care cascade and to accelerate the demonstration to scale processes. This proof of concept project, proposed by the consortium, and supported by the MRC South Africa, aims to implement and evaluate an adherence monitoring system (using the Wisepill evriMED device) with a differentiated response to patient care, among drug-sensitive TB (DS-TB) patients in three provinces of South Africa. Aims: This study aims to implement and evaluate the use of an adherence monitoring system (using the Wisepill evriMEDdevice) with a differentiated response to patient care, among drug-sensitive TB patients in three provinces of South Africa. Primary Objective: i) To evaluate whether implementation of the Wisepill evriMEDdevice with real-time monitoring and differentiated care is able to increase the proportion of patients with >90% adherence to DS-TB treatment
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TB MATE
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Devices
Anticipated trial start date 01/02/2019
Actual trial start date
Anticipated date of last follow up 01/03/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 2610
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Numbered containers Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group medical monitor EvriMed Device and differentiated care approach Automated daily reminders (light or sound) from EvriMed devices to take treatment. Monthly reminders from the devices for monthly refills. If patient misses one dose, they will receive an automated sms reminder . If they miss 2 or 3 doses, they will receive voice call by nurse or counsellor. If they receive 4 or more doses, then a home visit or clinic visit will be done. This will also require for other adherence measures such as motivational counselling to be done. 6 months or as long as patient is on drug-sensitive TB treatment. Patients enrolled in clinics allocated to this arm, will receive the differentiated care adherence package. This will include standard patient education, a medication monitor (EvriMED) which will alert patients (using sound and a light on the box) on a daily basis as a reminder to take their medication and reminders monthly for dispensing visits and will send messages to a central database that will allow for real-time monitoring. A step-wise approach to missed doses will be implemented which would include phone calls, home visits and motivational counselling for those who consistently missed medication doses. 1305
Control Group Enhanced standard of care Patients enrolled in clinics allocated to this arm, will receive patient education on TB adherence and a medication box (evriMED) that will silently measure treatment adherence. The medication box will not have alerts to remind patients of treatment. Information on treatment adherence (medication box opening data) will only be collected by the study team and will not be available to clinicians. No change in patient management will be enacted from information from the box. Patients will receive the standard adherence support provided by the clinic based on self-reporting and monthly medication collection 6 months or as long as patient is taking drug-sensitive treatment Patients enrolled in clinics allocated to this arm, will receive patient education on TB adherence and a medication box (evriMED) that will silently measure treatment adherence. The medication box will not have alerts to remind patients of treatment. Information on treatment adherence (medication box opening data) will only be collected by the study team and will not be available to clinicians. No change in patient management will be enacted from information from the box. Patients will receive the standard adherence support provided by the clinic based on self-reporting and monthly medication collection 1305 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
All patients (children and adults) either initiating or started TB treatment within the last 7 days at selected health facilities Adults willing and able to provide written informed consent to participate , and children, whose caregiver is willing and able to provide assent for participation Patients agree to use the Wisepill evriMED device and to have follow up including text messaging and phone calls Living within the study area and willing to inform the study team of any change of address during the treatment and follow-up period Drug-resistant TB patients Patients/carer of patient cannot use the Wisepill evriMed device after training patient/care of patient does not have a functional mobile phone 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 2 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/11/2018 University of Witswatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Pricess of Walles Terrace, Parktown, Johannesburg Johannesburg 2041 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/09/2018 University of Cape Town Faculty of Health Sciences Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
E53 Room 46, Old Main Building, Groote Schuur Hospital Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/11/2018 London School of Hygiene and Tropical Medicine
Ethics Committee Address
Street address City Postal code Country
Keppel Street London 1110 United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary study endpoint for treatment adherence will be the percentage of patient-months where at least 20% of doses (equivalent to missing three of 15 doses) were missed (“poor adherence”). End of TB treatment
Secondary Outcome Treatment success which will be measured as the proportion of patients that either have a documented cure or treatment completion by 210 days following commencement of TB treatment. We will aim to do a TB culture at the end of treatment to determine response to treatment. End of TB treatment
Secondary Outcome TB recurrence effectiveness which will be defined as incidence of TB cases one year post intervention meeting, in patients enrolled in intervention clinics compared to SOC clinics. The definition for • Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children • Clinical tuberculosis: Started on treatment for TB in adults and children 6 and 12 months post treatment completion
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
The Aurum Institute 29 Queens Road, Parktown, Johannesburg Johannesburg South Africa
Desmond Tutu HIV Foundation Anzio Road , Observatory Cape Town South Africa
Interactive Research Development 64 Grant Avenue Johannesburg South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Stop TB Partnership TB REACH Le Grand-Saconnex Geneva Switzerland
South African Medical Research Council Francie van Zyl Drive Parrow Valley Cape Town South Africa
Bill and Melinda Gates Foundation 5th Floor, 44 Melrose Boulevard Melrose Arch Johannesburg South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Bill and Melinda Gates Foundation 5th Floor, 44 Melrose Boulevard Melrose Arch Johannesburg 2196 South Africa Charities/Societies/Foundation
Secondary Sponsor South African Medical Research Council Francie van Zijl Drive, Parowvallei Cape Town South Africa Charities/Societies/Foundation
Secondary Sponsor Stop TB Partnership TB REACH 1218 Le Grand-Saconnex, Geneva Syrian Arab Republic Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Katherine Fielding Keppel Street London United Kingdom
Catherine Orrell Anzio Observatory Cape Town South Africa
Thulani Mbatha 64 Grant Ave Norwood Johannesburg 2192 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Salome Charalambous scharalambous@auruminstitute.org +270105901389 29 Queens Road, Parktown,
City Postal code Country Position/Affiliation
Johannesburg South Africa Deputy Scientific Officer
Role Name Email Phone Street address
Public Enquiries Rene Wills rwills@auruminstitute.org +270105901399 29 Queens Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg South Africa Regulatory Manager
Role Name Email Phone Street address
Scientific Enquiries Noriah Maraba nmaraba@auruminstitute.org +270105901446 29 Queens Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg South Africa Senior Research Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
No
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation to intervention 08/02/2019 We previously completed this section incorrectly. In this study clinics will be randomised into control or intervention arm Non-randomised Randomised
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation sequence 08/02/2019 we previously completed this section incorrectly. Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification
Section Name Field Name Date Reason Old Value Updated Value
Study Design Stratification factors 08/02/2019 We previously completed this section incorrectly. Urban/rural location, the total number of patients starting TB treatment per month, and treatment outcomes in the last 12 month
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation concealment 08/02/2019 Golf balls will be used to allocate clinics to control or intervention arms. Numbered containers
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 11/02/2019 pactr update Undecided No
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 12/11/2020 Update requested by researcher Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 03/02/2021 Recruitment completed on 31 Dec 2020 Recruiting Closed to recruitment,follow-up continuing