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Completed

NCT Number: NCT01075152

Cryptococcal Optimal ART Timing Trial

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.

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Key information

Conditions

Cryptococcal Meningitis AIDS Acquired Immunodeficiency Syndrome Bacterial Infections and Mycoses Blood-Borne Infections Central Nervous System Diseases Central Nervous System Fungal Infections Central Nervous System Infections Communicable Diseases Cryptococcosis Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Meningitis Meningitis, Cryptococcal Meningitis, Fungal Mycoses Nervous System Diseases Neuroinflammatory Diseases RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

14 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

GF Jooste Hospital, Cape Town, South Africa

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Efavirenz

Drug

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

Other names: sustiva

nucleoside

Biological

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

Other names: zidovudine or stavudine, lamivudine

Primary outcomes

  1. 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 outcomes

  1. Incidence of Immune Reconstitution Inflammatory Syndrome

    Time frame: 46 weeks

    Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.

  2. Incidence of Cryptococcal-relapse

    Time frame: 46 weeks

    Incidence of culture positive cryptococcal meningitis relapse

  3. 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.

  4. 46-week Survival

    Time frame: 46 weeks

    46-week survival by time-to-event analysis of all subjects enrolled

  5. HIV-1 Viral Suppression

    Time frame: 26 weeks

    HIV-1 virologic suppression to <400 copies/mL at 26-weeks after enrollment

  6. Antiretroviral Therapy Tolerability

    Time frame: 26 weeks

    Incidence of antiretroviral therapy interruption by >=3 consecutive days

  7. 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

  8. 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 outcomes

  1. 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).

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Collaborators

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

Registry information

Official study title

Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis

Acronym: COAT

Important dates

Study start
2010
Primary completion
2012
Study completion
2013
First posted
Feb 24, 2010
Registry last updated
Jun 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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