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Clinical Trials

MainTitle

Cryptococcal Optimal ART Timing Trial (COAT)

This study has been completed
Sponsor
University of Minnesota - Clinical and Translational Science Institute

Collaborator
Mbarara University of Science and Technology
Makerere University
National Institute of Allergy and Infectious Diseases (NIAID)
University of Cape Town

Information provided by (Responsible Party)
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier
NCT01075152

First received: February 23, 2010
Last updated: August 13, 2015
Last Verified: August 2015
History of Changes
Purpose

Purpose

The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient.

Condition Intervention Phase
Cryptococcal Meningitis
HIV Infections
AIDS

Drug : efavirenz
Biological : nucleoside
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures

  • Mortality [ Time Frame: 26 weeks from study entry ]
    Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
Secondary Outcome Measures:
  • Incidence of Immune Reconstitution Inflammatory Syndrome [ Time Frame: 46 weeks ]
    Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
  • Incidence of Cryptococcal-relapse [ Time Frame: 46 weeks ]
    Incidence of culture positive cryptococcal meningitis relapse
  • Safety of ART Initiation [ Time Frame: 46 weeks ]
    Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.
  • 46-week Survival [ Time Frame: 46 weeks ]
    46-week survival by time-to-event analysis of all subjects enrolled
  • HIV-1 Viral Suppression [ Time Frame: 26 weeks ]
    HIV-1 virologic suppression to <400 copies/mL at 26-weeks after enrollment
  • Antiretroviral Therapy Tolerability [ Time Frame: 26 weeks ]
    Incidence of antiretroviral therapy interruption by >=3 consecutive days
  • Karnofsky Functional Status [ Time Frame: 46 weeks ]
    Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
  • Microbiologic Clearance [ Time Frame: 4 weeks ]
    Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.
Other Outcome Measures:
  • Percentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26 [ Time Frame: 26 weeks ]
    Percentage of Participants who died by week 26 based on CSF white blood cell (WBC) count at study entry (time of randomization at a median of 8 days of anti-fungal therapy).

Enrollment: 177
Study Start Date: November 2010
Study Completion Date: March 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Earlier HIV Therapy
HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
Drug: efavirenz

Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

Other Name: sustiva
Biological: nucleoside

Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

Other Name:
  • zidovudine or stavudine
  • lamivudine

Active Comparator: Deferred HIV Therapy
HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week). HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
Drug: efavirenz

Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

Other Name: sustiva
Biological: nucleoside

Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

Other Name:
  • zidovudine or stavudine
  • lamivudine

Detailed Description:

After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:

  • Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR
  • Standard initiation of ART (Control Group) = ART at >=4 weeks after study entry
HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.

Eligibility

Eligibility

Ages Eligible for Study: 14 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • HIV-infection, documented by ELISA
  • Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
  • Age >14 years
  • Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
  • Ability and willingness of the participant or legal guardian/representative to give informed consent.
  • Receiving amphotericin-based anti-fungal therapy


Exclusion Criteria:
  • Study entry prior to receipt of <7 days or >11 days of amphotericin therapy
  • History of prior, known cryptococcal meningitis
  • Inability to take enteral medication
  • Receiving chemotherapy or other immunosuppressant medications
  • Cannot or unlikely to attend regular clinic visits
  • Contraindication to immediate or delayed HIV therapy based on serious co-morbidities or co-infections, or laboratory values
  • Pregnancy or Breastfeeding
  • Female participants of childbearing potential who are participating in sexual activity
that could lead to pregnancy must agree to use two reliable methods of contraception

contacts and locations

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01075152

Locations

South Africa
GF Jooste Hospital
Cape Town, South Africa
Uganda
Infectious Disease Institute, Mulago Hospital, Makerere University
Kampala, Uganda
Mbarara University of Science and Technology
Mbarara, Uganda

Sponsors and Collaborators

University of Minnesota - Clinical and Translational Science Institute
Mbarara University of Science and Technology
Makerere University
National Institute of Allergy and Infectious Diseases (NIAID)
University of Cape Town

Investigators

Principal Investigator: David R Boulware, MD, MPH University of Minnesota - Clinical and Translational Science Institute
More Information

More Information

Additional Information:

NIH NIAID FAQ on COAT Trial (Preliminary Results)

Additional Information:

N Engl J Med 2014 - Final Results

Responsible Party: University of Minnesota - Clinical and Translational Science Institute  
ClinicalTrials.gov Identifier: NCT01075152   History of Changes  
Other Study ID Numbers: DAIDS-ES ID 10795  
  U01AI089244  
Study First Received: February 23, 2010  
Last Updated: August 13, 2015  

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

cryptococcal meningitis
cryptococcus
cryptococcosis
HIV
AIDS
strategy

Additional relevant MeSH terms:
HIV Infections
Meningitis
Meningitis, Cryptococcal
Lamivudine
Efavirenz

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.