Clinical trial NCT03969030: Peer-Educator-coordinated vs Nurse-coordinated ART Refill for Adolescents and Young Adults Living With HIV in Lesotho
Official title: Peer-Educator-coordinated vs Nurse-coordinated ART Refill for Adolescents and Young Adults Living With HIV in Lesotho - a Cluster Randomized Clinical Trial (PEBRA Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV/AIDS
Keywords: HIV
Sub-Sahara Africa
Lesotho
Differentiated Service Delivery
Adolescents and young adults living with HIV
ART service
Preference-based
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: International AIDS Society (CIPHER grant)
name: Swiss Tropical & Public Health Institute
name: SolidarMed
name: Sentebale
name: University of Basel
name: University Hospital, Basel, Switzerland
name: Swiss National Science Foundation
First posted: 2019-05-31
Enrollment: 307
Sex: ALL
Minimum age (years): 15
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PEBRA study is a cluster randomized, open-label, superiority trial in a resource-limited setting
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Sub-Saharan Africa (SSA) is home to 85% of the adolescents and young people living with HIV (AYPLHIV) globally and they are heavily affected by the HIV/AIDS epidemic: AYPLHIV in SSA are the only population group for whom HIV-related mortality continues to increase, and they have overall poorer outcomes than all other age groups. Lesotho with worldwide the second-highest HIV prevalence shows a viral suppression rate among AYPLHIV of only 49%.

In order to address the multiple barriers in the adolescent HIV care cascade and their unique needs, multicomponent packages of differentiated service delivery (DSD) are a promising approach.

In close collaboration with different local stakeholders, the researchers designed a DSD model specifically for AYPLHIV, called the PEBRA model. In the PEBRA model the peer-educator (PE) plays a pivotal role, by coordinating the ART refill/care according to the patient's preferences using a tablet-based application, called PEBRApp (https://github.com/chrisly-bear/PEBRApp). The PEBRApp helps the PE to assess each participant's preference, to adapt the ART refill according to these preferences in a feasible manner, to keep track of the ART refill, and to ensure regular contact between the PE and the participant. The model includes key innovative options such as individualized automatic SMS notifications and decentralized ART delivery.

The PEBRApp was developed with ❤️ by Technify Maseru, Lesotho (www.technifyls.com) \& Christoph Schwizer Zurich, Switzerland (www.christophschwizer.ch).

Detailed description: STUDY DESIGN

PEBRA study is a cluster randomized, open-label, superiority trial in a resource-limited setting. The rational for a cluster randomized design with health facilities as clusters, is the high risk of cross-contamination between the study arms if randomization would be done at individual level. The clusters (health facilities) will be randomized (randomly-varying block sizes, 1:1 allocation) into the 2 groups using a computer-generated randomization list, stratified by district and size of the AYPLHIV cohort of each facility (\<15 vs ≥15). The study will be conducted at 20 health facilities in three districts of Lesotho (Leribe, Butha-Buthe, Mokhotlong).

OBJECTIVES

The overall objective of this study is to evaluate the feasibility and effectiveness of a DSD model ("PEBRA model") among AYPLHIV.

As primary objective this study seeks to assess the rate of viral suppression among AYPLHIV 12 months after enrolment between the intervention clusters, where AYPLHIV were offered the PEBRA model, and the control clusters, where AYPLHIV were offered standard of care.

Secondary objectives include a comparison of adherence to ART, the level of perceived quality of ART care and patient service satisfaction, engagement in care, viral suppression, lost-to-follow-up (LTFU), mortality, and transfer out between the intervention and control clusters. Further objectives include a cost-effectiveness evaluation and qualitative research regarding acceptance, scalability and feasibility of the DSD model.

QUALITATIVE RESEARCH

Besides above outlined qualitative research (QoL, QoC, longitudinal description of participants' preference assessments) the researchers will explore the acceptability of the PEBRA model in a) Focus Group Dis-cussions (FGD) with study participants from the intervention clusters, and b) key informant interviews (KII) with the main stakeholders (District Health Management Team and different health center staff). We plan to conduct at least 2 FGD (with about 5 study participants) per district and 3 KII per district, ac-cording to the concept of saturation. Data will be collected by trained facilitators using piloted interview questionnaires and discussion guides, in the local language (Sesotho). Qualitative data will be record-ed, transcribed, translated into English and coded and analyzed using the Framework Method. All participants in this qualitative research will be required to sign a separate consent form to participate and to be recorded. These consent forms and interview questionnaires will be submitted as an amendment to the ethics committee in Lesotho at a later stage.

COST-EFFECTIVENESS ANALYSIS AND SYSTEM IMPACT EVALUATION

The researchers will perform a system impact evaluation and cost-effectiveness analysis, in order to estimate the im-pact of the PEBRA model on health benefits and costs. First, we will assess the direct costs of the PEBRA model. Secondly, we will assess the cost-effectiveness of the PEBRA model. Thirdly, we will as-sess the economic burden of the PEBRA model to the study participants, i.e. including both direct costs and the opportunity costs of their time. The assessment of direct costs includes staff costs (PEs, clinic staff, VHWs), personnel training costs (especially for the PEs), the cost of equipment needed (PEBRApp, logistics), medical costs to the participant (medication, laboratory tests, consumables, etc.), and non-medical costs to the participant (i.e. cost of transportation to ART service). Data to assess pa-tient level costs will be collected from a randomly selected sub-sample of study participants from each cluster arm, using medical expenditure records and interviews. Cost outcomes will include:

i) The average cost to the service provider per patient achieving the primary endpoint at 12 months in each cluster arm ('per patient suppressed provider cost') ii) The average cost to the patient per patient achieving the primary endpoint at 12 months in each cluster arm ('per patient suppressed patient cost') iii) The annual cost per patient in each cluster arm ('per patient year cost') iv) The cost-effectiveness of the PEBRA model with respect to viral suppression and engage-ment in care Costs will be reported as means (incl. standard deviations) and medians (incl. interquartile range) in local currency and US dollar and International Dollar.

PREFERENCE AND FEASIBILITY ASSESSMENT

The researchers will systematically assess the following exploratory analyses regarding feasibility and youth ART service preference:

1. Youth ART service preferences: Longitudinal description of participants' preference assessments
2. Feasibility of youth ART service according to preferences: Percentage of ART service delivered according to participants' preferences
3. Differentiated Impact of the different support options on key study outcomes

PILOT TRIAL

PEBRA model will be piloted at one representative health facility in Butha-Buthe district, that will be pragmatically chosen in collaboration with the District Health Management Team. The pilot trial will be crucial to assess feasibility of the PEBRA model and the study procedures. The same procedures apply in the pilot trial as in the main trial, using the same consent process and baseline data collection. One PE will be specifically trained for the pilot. Recruitment for the pilot will be closed once 3-5 study participants are enrolled and follow-up will last for 2.5 months after having enrolled the last participant. All endpoints that are evaluable "at 3 months (range 2.5 - 3.5)" will be assessed and analyzed. The aim of the pilot trial is to give a first insight into PEBRA model and provide detailed information for the main trial.

Eligibility criteria: Eligibility - clusters

Inclusion criteria:

1. the cluster is a public or missionary health center from the study districts, that offers ART services
2. the cluster has at least one PE who is willing to participate and fulfills the following criteria:

   1. underwent the Sentebale Peer-Educator two-weeks training
   2. attended and successfully passed the study training assessment

Exclusion criteria:

1. health facility authority opposed to trial participation (verbal assent)
2. the health facility is a hospital
3. the health facility is situated in an area without cellphone signal

Eligibility - individuals

1. Individual is living with HIV and in care in a participating cluster
2. Individual is 15-24 years old (AYPLHIV)
3. Informed consent given
4. Declares to seek the next follow-up visit at the same health facility

Primary outcomes:
measure: In care with documented viral suppression
timeFrame: 12 months (range: 9 - 15 months) after enrolment
Secondary outcomes:
measure: Adherence to ART at 3 months (range 2.5 - 3.5), 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
timeFrame: 3 months (range 2.5 - 3.5), 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
measure: Quality of Life (QoL) at 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
timeFrame: 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
measure: Perceived quality of ART Care / patient service satisfaction at 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
timeFrame: 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
measure: Engagement in care at 6 months
timeFrame: 6 months (range 5 - 8) after enrolment
measure: Alternative viral suppression at 12 months
timeFrame: 12 months (range 9 - 15) after enrolment
measure: Engagement in care at 12 months
timeFrame: 12 months (range 9 - 15) after enrolment
measure: All-cause mortality
timeFrame: 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
measure: LTFU at 6 and 12 months
timeFrame: 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
measure: Transfer out at 6 and 12 months
timeFrame: 6 months (range 5 - 8) and 12 months (range 9 - 15) after enrolment
Other outcomes:
measure: Serious Adverse Events (SAE)
timeFrame: within 12 months after enrolment
Locations:
city: Butha-Buthe
country: Lesotho
facility: Boiketsiso HC
city: Butha-Buthe
country: Lesotho
facility: Linakeng HC
city: Butha-Buthe
country: Lesotho
facility: Makhunoane HC
city: Butha-Buthe
country: Lesotho
facility: Motete HC
city: Butha-Buthe
country: Lesotho
facility: Muela HC
city: Butha-Buthe
country: Lesotho
facility: Ngoajane HC
city: Butha-Buthe
country: Lesotho
facility: Rampai HC
city: Butha-Buthe
country: Lesotho
facility: St. Paul HC
city: Butha-Buthe
country: Lesotho
facility: St. Peters HC
city: Butha-Buthe
country: Lesotho
facility: Tsime HC
city: Leribe
country: Lesotho
facility: Ha Lejone HC
city: Leribe
country: Lesotho
facility: Pontmain
city: Mokhotlong
country: Lesotho
facility: Libibing HC
city: Mokhotlong
country: Lesotho
facility: Linakaneng HC
city: Mokhotlong
country: Lesotho
facility: Malefiloane HC
city: Mokhotlong
country: Lesotho
facility: Mapholaneng HC
city: Mokhotlong
country: Lesotho
facility: Moeketsane HC
city: Mokhotlong
country: Lesotho
facility: Molikaliko HC
city: Mokhotlong
country: Lesotho
facility: St. James HC
city: Mokhotlong
country: Lesotho
facility: St. Martins HC
Study officials:
affiliation: Swiss TPH & University Hospital Basel & University of Basel
name: Niklaus Labhardt, MD MIH
role: STUDY_CHAIR
affiliation: Swiss TPH & University Hospital Basel & University of Basel
name: Alain Amstutz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SolidarMed
name: Mathebe Kopo
role: STUDY_DIRECTOR
affiliation: Swiss TPH & University of Basel
name: Jennifer Brown, MSc
role: STUDY_DIRECTOR
affiliation: Swiss TPH & University of Basel
name: Nadine Bachmann, MSc
role: STUDY_DIRECTOR
affiliation: SolidarMed
name: Thabo Lejone, MIH
role: STUDY_DIRECTOR
affiliation: DHMT BB
name: Lebohang Sao, MD
role: STUDY_DIRECTOR
affiliation: Swiss TPH & University of Basel
name: Tracy Glass, PhD
role: STUDY_DIRECTOR
References:
citation: Lejone TI, Kopo M, Bachmann N, Brown JA, Glass TR, Muhairwe J, Matsela T, Scherrer R, Chere L, Namane T, Labhardt ND, Amstutz A. PEBRA trial - effect of a peer-educator coordinated preference-based ART service delivery model on viral suppression among adolescents and young adults living with HIV: protocol of a cluster-randomized clinical trial in rural Lesotho. BMC Public Health. 2020 Mar 30;20(1):425. doi: 10.1186/s12889-020-08535-6.