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An Enhanced Package of Care to Reduce Reduce Mortality in Advanced HIV Disease (ENCORE)

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ClinicalTrials.gov Identifier: NCT05085171
Recruitment Status : Recruiting
First Posted : October 20, 2021
Last Update Posted : July 12, 2022
Sponsor:
Collaborator:
University of Minnesota
Information provided by (Responsible Party):
Makerere University

Tracking Information
First Submitted Date  ICMJE October 8, 2021
First Posted Date  ICMJE October 20, 2021
Last Update Posted Date July 12, 2022
Actual Study Start Date  ICMJE May 4, 2022
Estimated Primary Completion Date March 1, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2021)		 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2021)
  • Evaluate sensitivity and specificity of the different TB point of care tests. [ Time Frame: 24 weeks ]
    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
  • Incidence of OIs and associated hospitalization and mortality [ Time Frame: Six months ]
    Incidence of active TB within 6 months, Incidence of cryptococcal meningitis and associated mortality.
  • Tolerability and adherence to prophylaxis regimen and associated grade 3 to 5 adverse events [ Time Frame: 24 weeks ]
    percentage completion of regimen and proportions that get grade 3 and above AEs.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Enhanced Package of Care to Reduce Reduce Mortality in Advanced HIV Disease
Official Title  ICMJE A Community-based Phase III, Cluster Randomized Trial of Point-of-care CD4 Testing and Enhanced Screening and Prophylaxis in Advanced HIV Disease
Brief 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.
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

  1. Point-of-care CD4 testing via Visitect (point of care semi Quantitaive CD4 LFA) lateral flow assay (LFA)

  2. 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

  1. CD4 testing by flow cytometry

  2. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention 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)
Primary Purpose: Other
Condition  ICMJE The Study Will Focus on Assessing the Survival Benefit on an Enhanced Package of Care for Patients With Advanced HIV Disease
Intervention  ICMJE Other: Enhanced care package
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 Arms  ICMJE
  • Experimental: intervention(Enhanced package of care) Arm
    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.
    Intervention: Other: Enhanced care package
  • No Intervention: Standard of care Arm
    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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2021)		 2400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2027
Estimated Primary Completion Date March 1, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age >18 years
  • CD4<200 cells/µL
  • Ability and willingness to give informed consent for the enhanced package of care arm.

Exclusion Criteria:

  • Known virologic suppression (viral load <1000 copies/mL) within prior 3 months
  • Cannot or unlikely to attend regular clinic visits
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Radha Rajasingham, MD 612 626-8171 radha@umn.edu
Contact: Elizabeth Nalintya, MBChB,MPH 0414307000 nalintyaelizabeth@gmail.com
Listed Location Countries  ICMJE Uganda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05085171
Other Study ID Numbers  ICMJE IDIREC REF 007/2021
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Aggregated patient data will be summarized and disseminated.
Current Responsible Party Makerere University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Makerere University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University of Minnesota
Investigators  ICMJE Not Provided
PRS Account Makerere University
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP