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A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV

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ClinicalTrials.gov Identifier: NCT03154320
Recruitment Status : Recruiting
First Posted : May 16, 2017
Last Update Posted : August 22, 2018
Sponsor:
Collaborators:
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Weill Medical College of Cornell University
Florida International University
University of California, Davis
Analysis Group, Inc.
Information provided by (Responsible Party):
Serena Patricia Koenig, Brigham and Women's Hospital

Brief Summary:
This is a randomized, unblinded study comparing standard vs. same-day treatment for patients with TB symptoms (cough, fever, night sweats, or weight loss) at HIV diagnosis. Six hundred patients will be randomized in a 1:1 ratio to the standard group or the same-day treatment group. All study activities will take place at the GHESKIO Centers in Port-au-Prince, Haiti. The study population includes HIV-infected men and women ≥18 years of age who are ART-naïve, and who present with symptoms of TB (cough, fever, nights sweats, or weight loss) at HIV diagnosis.

Condition or disease Intervention/treatment Phase
HIV/AIDS Tuberculosis Other: Same-Day Treatment Other: Standard treatment Not Applicable

Detailed Description:

This study is a randomized trial that will compare outcomes with standard and same-day treatment among patients with TB symptoms at HIV diagnosis. The standard group will receive same-day chest x-ray as well as Xpert Ultra testing with a spot specimen (with 48-hour turn-around-time). Participants will return for Xpert Ultra results and early morning sputum testing on Day 2. TB treatment will be provided on the day of diagnosis (Day 0 for those with high clinical and radiographic suspicion of TB, and Day 2 for those diagnosed by Xpert Ultra). Standard group participants who are not diagnosed with TB will be tested and treated for other opportunistic infections (OIs), as clinically indicated, and will initiate ART on Day 7. The same-day group will receive Xpert Ultra testing (with same-day results) and chest x-ray with same-day ART or TB treatment (on Day 0) based on test results. They will also be tested and treated for other OIs as clinically indicated. They will provide early morning sputum for repeat testing on Day 1. Both groups will receive Xpert Ultra testing on both spot and early morning specimens, with liquid culture on both specimens as the diagnostic gold standard; those with TB will start ART according to WHO guidelines.

Three specific aims are proposed:

Aim 1: To compare the proportion of participants in each group who are alive and in care with undetectable viral load (<200 copies/ml) at 48 weeks after HIV testing. Hypothesis: The proportion of participants retained in care with undetectable viral load will be 51% in the standard and 65% in the same-day group.

Aim 2: To compare mortality in each group at 48 weeks after HIV testing. Hypothesis: Mortality will be 10% in the standard group and 4% in the same-day group.

Aim 3: To conduct a comparison of cost and cost-effectiveness of standard and same-day care, where cost is measured by the mean treatment cost and effectiveness is measured by being alive and in care with plasma HIV-1 RNA level <200 copies/ml at 48 weeks after HIV testing. Hypothesis: Same-day treatment will cost less per patient retained in care with undetectable viral load.

Aim 4: To determine the rates of ART and TB treatment initiation, TB diagnosis after ART initiation, IRIS, adverse events, and adherence in both groups, and to evaluate the sensitivity, specificity, and predictive values of single tests and different testing combinations compared to liquid mycobacterial culture results.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized in a 1:1 ratio to standard or same-day treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Trial of Same-Day Testing and Treatment to Improve Outcomes Among Symptomatic Patients Newly Diagnosed With HIV
Actual Study Start Date : November 6, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Standard Group
On Day 0 (day of HIV diagnosis and study enrollment) participants will receive a chest x-ray and provide a sputum specimen for spot Xpert Ultra testing (48-hour results). Those with high clinical/radiographic suspicion for TB will start same-day TB treatment. On Day 2, participants will return for results of Xpert Ultra testing (spot specimen) and to provide a specimen for early morning Xpert Ultra testing. Those who are Xpert Ultra positive will start TB treatment. Those who are not diagnosed with TB will start ART on Day 9, after testing and treatment for other opportunistic infections. A liquid TB culture will be performed on both the spot and early morning specimens.
Other: Standard treatment
Standard treatment

Experimental: Same-Day Treatment Group
On Day 0 (day of HIV diagnosis and study enrollment) participants will receive a chest x-ray and Xpert Ultra testing with same-day results. Based on clinical symptoms, Xpert Ultra results, and chest x-ray, physician will determine whether or not the participant has tuberculosis. Those who are diagnosed with TB will start same-day TB treatment. Those who are not diagnosed with TB will start same-day ART.
Other: Same-Day Treatment
Treatment with ART or TB medication on day of HIV diagnosis




Primary Outcome Measures :
  1. Retention in care with viral suppression [ Time Frame: 48 weeks after HIV testing ]
    Proportion of participants who are in care with HIV-1 RNA <200 copies/ml


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 48 weeks after HIV testing ]
    All-cause mortality

  2. Mean treatment cost per participant [ Time Frame: 48 weeks after HIV testing ]
    Mean treatment cost per participant

  3. Viral suppression [ Time Frame: 48 weeks after HIV testing ]
    Proportion of participants with HIV-1 RNA <50 copies/ml and <1000 copies/ml

  4. Adherence by medication possession ratio [ Time Frame: 48 weeks after HIV testing ]
    Proportion of participants with 48-week adherence to ART of at least 90% by pharmacy refill records

  5. Adherence by 3-day self-report [ Time Frame: 48 weeks after HIV testing ]
    Proportion of participants with perfect (100%) adherence as measured by 3-day self-report at 48 weeks after HIV testing

  6. Treatment failure [ Time Frame: 48 weeks ]
    Proportion of participants meeting WHO criteria for ART failure and proportion initiating second-line ART during the study period

  7. TB testing characteristics [ Time Frame: These diagnostic tests will be conducted during the first week of study enrollment ]
    Sensitivity, specificity, predictive values, and likelihood ratios of spot and early morning Xpert Ultra results and chest x-ray, as single and as combined tests, with liquid culture as gold standard

  8. Time in clinic [ Time Frame: First study day and first study month ]
    Median time spent in clinic during first day and month of the study

  9. Coping with HIV diagnosis [ Time Frame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing ]
    Scores on the COPE survey

  10. Connectedness to Treatment Setting [ Time Frame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing ]
    Scores on the Connectedness to Treatment Setting Scale

  11. TB diagnosis after ART initiation [ Time Frame: 48-week study period ]
    Diagnosis of culture-positive TB after ART initiation (BACTEC MGIT 960, Becton Dickinson)

  12. Incidence of immune reconstitution inflammatory syndrome (IRIS) [ Time Frame: 48-week study period ]
    Incidence of paradoxical or unmasking IRIS

  13. Adverse events [ Time Frame: 48-week study period ]
    New Division of AIDS Grade 3 or Grade 4 signs, symptoms, or laboratory abnormalities that are at least a one-grade increase from baseline

  14. Measure of hope and optimism [ Time Frame: 2 Weeks, 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing ]
    Scores on the State Hope Scale

  15. Patient satisfaction [ Time Frame: 12 Weeks, 24 Weeks, and 48 Weeks after HIV Testing ]
    Scores on the HRSA Patient Satisfaction Survey

  16. Time to death [ Time Frame: 48-week study period ]
    Days to death

  17. Last missed dose of medication [ Time Frame: 2 Weeks, 12 Weeks, 24 Weeks, 48 Weeks ]
    Proportion of participants who report last missed dose of ART was at least 2 weeks ago



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women of ≥18 years of age
  • Presence of cough, fever, night sweats or weight loss
  • Ability and willingness to give written informed consent
  • Documentation of positive HIV status (test conducted at GHESKIO)
  • Acceptance of HIV diagnosis, defined as affirmative responses to two questions: "I believe that HIV and AIDS exist" and "I believe that the results of my HIV test show that I am infected".

Exclusion Criteria:

  • Any use of ART in the past
  • Treatment for TB in the year prior to screening visit
  • Pregnancy or breastfeeding at the screening visit
  • Active drug, alcohol use, or mental condition that would interfere with the ability to adhere to study requirements, in the opinion of the study physician
  • Score of <3 for any of the 7 questions on the ART readiness survey
  • Planning to transfer care to another clinic during the study period
  • Symptoms consistent with WHO stage 4 neurologic disease (cryptococcal meningitis, TB meningitis; central nervous system toxoplasmosis; HIV encephalopathy; progressive multifocal leukoencephalopathy)
  • Severe illness, classified as one of the WHO "danger signs" of temperature >39 degrees Celsius, pulse >120 beats/minutes, respiratory rate >30, or inability to walk unaided.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03154320


Contacts
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Contact: Serena P Koenig, MD 617-413-4090 skoenig@bwh.harvard.edu
Contact: Patrice Severe, MD 011-509-2940-1430 patsevere@gheskio.org

Locations
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Haiti
GHESKIO Recruiting
Port-au-Prince, Haiti
Contact: Jean W Pape, MD    01150929401430    jwpape@gheskio.org   
Contact: Patrice Severe, MD    01150929401430    patsevere@gheskio.org   
Sponsors and Collaborators
Brigham and Women's Hospital
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Weill Medical College of Cornell University
Florida International University
University of California, Davis
Analysis Group, Inc.
Investigators
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Principal Investigator: Serena P Koenig, MD Brigham and Women's Hospital

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Responsible Party: Serena Patricia Koenig, Associate Physician, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03154320     History of Changes
Other Study ID Numbers: AI131998
First Posted: May 16, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: When the study has been completed, anonymized data will be made publicly available, which will permit replication of reported outcomes.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections