The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV DiseasePhase 3ENCORENCT05085171
An Enhanced Package of Care to Reduce Reduce Mortality in Advanced HIV Disease
A Phase 3 study testing Enhanced care package in people with The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease, run by Makerere University at 1 site in Uganda.
Trial summary
A community-based Phase III, cluster randomized trial that seeks to determine the 24 week survival with retention in care of point of care CD4 testing with visitect and an enhanced package of screening and prophylaxis for opportunistic infections among patients with advanced HIV disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease
- What is being tested?
- Enhanced care package
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,400 participants
- Where
- 1 siteUganda
- Study dates
- 4 May 2022to 1 Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- CD4<200 cells/µL
- Ability and willingness to give informed consent for the enhanced package of care arm.
Who cannot join
- Known virologic suppression (viral load <1000 copies/mL) within prior 3 months
- Cannot or unlikely to attend regular clinic visits
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda1 site, 1 recruiting
- Recruiting
kisugu health center IV
Kampala
Teopista Namuli
About this study
Official title: A Community-based Phase III, Cluster Randomized Trial of Point-of-care CD4 Testing and Enhanced Screening and Prophylaxis in Advanced HIV Disease
A community-based Phase III, cluster randomized trial that seeks to determine the 24 week survival with retention in care of point of care CD4 testing with visitect and an enhanced package of screening and prophylaxis for opportunistic infections among patients with advanced HIV disease.
Read the detailed description
The study will be carried out in a population of HIV-infected adults with advanced HIV disease (CD4 <200 cells/µL) in Uganda. It will be a Randomized controlled trial, Phase III in Uganda over a duration of 5 years assessing 24 weeks survival with retention in care. @4 clinic will be randomized to either receive the enhanced package or standard of care.
Description of Intervention Arm
- Point-of-care CD4 testing via Visitect (point of care semi Quantitaive CD4 LFA) lateral flow assay (LFA)
- Enhanced package of opportunistic infection screening and prophylaxis for CD4<200, including:
- FujiFilm SILVAMP TB LAM (FujiLAM)
- Isoniazid (INH) + rifapentine: 1 month of therapy for latent TB(Tuberculosis) infection
- Cryptococcal Antigen semi-quantitative (CrAg-SQ) LFA (Immy)
- Treatment for disseminated CNS cryptococcal infection if high blood CrAg titer (>3+ CrAg SQ)
Description of Standard of Care Arm
- CD4 testing by flow cytometry
- WHO recommended package of OI screening and prophylaxis, including:
- Urine TB LAM
- INH ( isoniazid 6 months)
- CrAg LFA
- Fluconazole for asymptomatic CrAg+ o 800mg daily x 2 weeks, then 400mg daily x 8 weeks, then 200mg daily.
Problem statement: Current lab-based CD4 testing results in a delay to either start ART(Antiretroviral therapy) or a delay in screening persons with low CD4s for OIs. At present, prioritization has been on ART initiation without systematic OI screening. Those with subclinical OIs started on ART unmask their OIs, with hospitalization / deaths for OIs such as cryptococcosis and TB.
We hypothesize that with point of care CD4 testing, same-day OI screening can occur, yet not interrupt prompt ART initiation for those at low risk (FujiLAM and CrAg-SQ negative) of unmasking immune reconstitution syndrome.
We hypothesize that point-of-care CD4 testing will improve 6-month survival by reducing lag time in CD4 results, thereby facilitating ART initiation, retention-in-care, and OI screening and prophylaxis.
We hypothesize that enhanced screening with the point-of-care FujiLAM, CrAg-SQ LFA, with enhanced prophylaxis for TB (1 month of INH and rifapentine) and with treatment for disseminated CNS cryptococcal infection in those CrAg+ with high titers (>3+) will improve 6-month survival compared to current WHO-recommended standard practice in persons with advanced HIV disease.
- Being tested
- Enhanced care package
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enhanced care packageOther
The intervention is an improved package of care for patients with advanced HIV disease with point of care CD4 testing, more sensitive screening tests for opportunistic infections and more intensive pre-emptive treatment for opportunistic infections
| Study group | Role | What they receive |
|---|---|---|
| intervention(Enhanced package of care) Arm | Experimental | The patients with advanced HIV disease that receive HIV care at the intervention clinics will receive the enhanced intervention package which will include: point of care CD4 testing with visitect, screening for TB and cryptococcal meningitis using Fujifilm LAM and semiquantitative crAg LFA respectively and pre-emptive treatment with isoniazid and rifapentine for one month. Those with a high crAg titers will receive treatment for CNS cryptococcal disease. Receives: Other: Enhanced care package |
| Standard of care Arm | No intervention | The patients with advanced HIV disease that receive HIV care at the standard of care clinics will receive the usual routine HIV care as per the Uganda national guidelines. That is CD4 testing with flowcytometry or other CD4 testing modalities available, screening for TB and cryptococcal meningitis using Alere LAM and crAg LFA respectively and pre-emptive treatment with isoniazid and rifapentine for 3-6 month. Treatment of all asymptomatic crAG positives with fluconazole as per guidelines. |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-week survival with retention in care
Comparison will be made between study arms of those who receive POC CD4 testing vs. those who receive standard flow cytometry, and those who receive the enhanced package of OI screening and prophylaxis, vs. those who receive the current WHO standard.
Measured: 24 weeks
Secondary outcomes (3)
Evaluate sensitivity and specificity of the different TB point of care tests.
After a positive FujiFilm TB LAM test, incidence of Xpert-positive or culture positive TB, and clinical outcomes to distinguish between false positive vs. true positive urine tests
Measured: 24 weeks
Incidence of OIs and associated hospitalization and mortality
Incidence of active TB within 6 months, Incidence of cryptococcal meningitis and associated mortality.
Measured: Six months
Tolerability and adherence to prophylaxis regimen and associated grade 3 to 5 adverse events
percentage completion of regimen and proportions that get grade 3 and above AEs.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2021
- Study start4 May 2022
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- A community randomised controlled trial of 24 clinics,12 in the intervention arm and 12 in standard of care arm. Two levels of randomization planned
- Masking
- None (open label)
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05085171
- Sponsor's protocol ID
- IDIREC REF 007/2021
- Acronym
- ENCORE
- Status last verified
- Jul 2022
- First submitted
- 8 Oct 2021
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregated patient data will be summarized and disseminated.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Community-based Phase III, Cluster Randomized Trial of Point-of-care CD4 Testing and Enhanced Screening and Prophylaxis in Advanced HIV Disease
- ClinicalTrials.gov ID
- NCT05085171
- Acronym / sponsor ID
- ENCORE / IDIREC REF 007/2021
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- University of Minnesota
- Study start
- 4 May 2022 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 20 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A community-based Phase III, cluster randomized trial that seeks to determine the 24 week survival with retention in care of point of care CD4 testing with visitect and an enhanced package of screening and prophylaxis for opportunistic infections among patients with advanced HIV disease.
Detailed description
The study will be carried out in a population of HIV-infected adults with advanced HIV disease (CD4 <200 cells/µL) in Uganda. It will be a Randomized controlled trial, Phase III in Uganda over a duration of 5 years assessing 24 weeks survival with retention in care. @4 clinic will be randomized to either receive the enhanced package or standard of care.
Description of Intervention Arm
- Point-of-care CD4 testing via Visitect (point of care semi Quantitaive CD4 LFA) lateral flow assay (LFA)
- Enhanced package of opportunistic infection screening and prophylaxis for CD4<200, including:
- FujiFilm SILVAMP TB LAM (FujiLAM)
- Isoniazid (INH) + rifapentine: 1 month of therapy for latent TB(Tuberculosis) infection
- Cryptococcal Antigen semi-quantitative (CrAg-SQ) LFA (Immy)
- Treatment for disseminated CNS cryptococcal infection if high blood CrAg titer (>3+ CrAg SQ)
Description of Standard of Care Arm
- CD4 testing by flow cytometry
- WHO recommended package of OI screening and prophylaxis, including:
- Urine TB LAM
- INH ( isoniazid 6 months)
- CrAg LFA
- Fluconazole for asymptomatic CrAg+ o 800mg daily x 2 weeks, then 400mg daily x 8 weeks, then 200mg daily.
Problem statement: Current lab-based CD4 testing results in a delay to either start ART(Antiretroviral therapy) or a delay in screening persons with low CD4s for OIs. At present, prioritization has been on ART initiation without systematic OI screening. Those with subclinical OIs started on ART unmask their OIs, with hospitalization / deaths for OIs such as cryptococcosis and TB.
We hypothesize that with point of care CD4 testing, same-day OI screening can occur, yet not interrupt prompt ART initiation for those at low risk (FujiLAM and CrAg-SQ negative) of unmasking immune reconstitution syndrome.
We hypothesize that point-of-care CD4 testing will improve 6-month survival by reducing lag time in CD4 results, thereby facilitating ART initiation, retention-in-care, and OI screening and prophylaxis.
We hypothesize that enhanced screening with the point-of-care FujiLAM, CrAg-SQ LFA, with enhanced prophylaxis for TB (1 month of INH and rifapentine) and with treatment for disseminated CNS cryptococcal infection in those CrAg+ with high titers (>3+) will improve 6-month survival compared to current WHO-recommended standard practice in persons with advanced HIV disease.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A community randomised controlled trial of 24 clinics,12 in the intervention arm and 12 in standard of care arm. Two levels of randomization planned
| Arm | Type | Receives |
|---|---|---|
| intervention(Enhanced package of care) Arm | Experimental | Other: Enhanced care packageThe patients with advanced HIV disease that receive HIV care at the intervention clinics will receive the enhanced intervention package which will include: point of care CD4 testing with visitect, screening for TB and cryptococcal meningitis using Fujifilm LAM and semiquantitative crAg LFA respectively and pre-emptive treatment with isoniazid and rifapentine for one month. Those with a high crAg titers will receive treatment for CNS cryptococcal disease. |
| Standard of care Arm | No intervention | –The patients with advanced HIV disease that receive HIV care at the standard of care clinics will receive the usual routine HIV care as per the Uganda national guidelines. That is CD4 testing with flowcytometry or other CD4 testing modalities available, screening for TB and cryptococcal meningitis using Alere LAM and crAg LFA respectively and pre-emptive treatment with isoniazid and rifapentine for 3-6 month. Treatment of all asymptomatic crAG positives with fluconazole as per guidelines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >18 years
- CD4<200 cells/µL
- Ability and willingness to give informed consent for the enhanced package of care arm.
Key exclusion criteria (2 listed)
- Known virologic suppression (viral load <1000 copies/mL) within prior 3 months
- Cannot or unlikely to attend regular clinic visits
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enhanced care packageThe intervention is an improved package of care for patients with advanced HIV disease with point of care CD4 testing, more sensitive screening tests for opportunistic infections and more intensive pre-emptive treatment for opportunistic infections | Other | intervention(Enhanced package of care) Arm |
Primary outcome
24-week survival with retention in care
Time frame: 24 weeks
Comparison will be made between study arms of those who receive POC CD4 testing vs. those who receive standard flow cytometry, and those who receive the enhanced package of OI screening and prophylaxis, vs. those who receive the current WHO standard.
3 secondary outcomes
Evaluate sensitivity and specificity of the different TB point of care tests.
Time frame: 24 weeks
Incidence of OIs and associated hospitalization and mortality
Time frame: Six months
Tolerability and adherence to prophylaxis regimen and associated grade 3 to 5 adverse events
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Individual participant dataSharing planned: No. Aggregated patient data will be summarized and disseminated.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enhanced care package in people with The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Radha Rajasingham, MD (612 626-8171, radha@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-week survival with retention in care (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.