Cryptococcal Optimal ART Timing Trial (COAT)
This study has been completed.
Sponsor:
University of Minnesota - Clinical and Translational Science Institute
Collaborators:
Mbarara University of Science and Technology
Makerere University
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: March 4, 2013
Last verified: March 2013
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Purpose
Detailed Description:
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 |
Other: Early HIV Therapy Initiation Other: Active Comparer Standard HIV Therapy Initiation |
Phase 4 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
Official Title: | Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis |
Resource links provided by NLM:
Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:
Primary Outcome Measures:
- Survival [ Time Frame: 26 weeks from study entry ] [ Designated as safety issue: Yes ]Intention to treat analysis of 26 week survival of all subjects enrolled.
Secondary Outcome Measures:
- Incidence of immune reconstitution inflammatory syndrome [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 26 weeks after enrollment.
- Incidence of Cryptococcal-relapse [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]Incidence of culture positive cryptococcal meningitis relapse
- Safety of ART Initiation [ Time Frame: 46 weeks ] [ Designated as safety issue: Yes ]Incidence of Adverse Events (Grade 3,4,5) through 46-weeks
- 46-week Survival [ Time Frame: 46 weeks ] [ Designated as safety issue: Yes ]46-week survival by time-to-event analysis of all subjects enrolled
- HIV-1 Viral Suppression [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]HIV-1 virologic suppression to <400 copies/mL at 26-weeks after enrollment
- Antiretroviral Therapy Tolerability [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]Incidence of antiretroviral therapy interruption by >3 consecutive days
- Function status [ Time Frame: 46 weeks ] [ Designated as safety issue: No ]Function status via Karnofsky performance status score at 4, 26, 46 weeks.
- Microbiologic Clearance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at screening, study entry, study day 7, any additional therapeutic lumbar punctures, and/or time of outpatient clinic registration (week 4).
Other Outcome Measures:
- Pre Specified Subgroups [ Time Frame: 46 weeks ] [ Designated as safety issue: No ]
- Altered mental status, Glasgow Coma Scale <=14 versus 15
Antigen burden
- Initial Diagnostic CSF quantitative culture
- Study entry CSF quantitative cultures
- Study entry: CRAG titer >1:2048
- Completion of Amphotericin: CSF culture positive (Study Day 7)
- Completion of Amphotericin: CRAG titer >1:1024 (Study Day 7)
- Low antigen burden (CSF culture negative, CSF CRAG positive at study entry)
- CSF inflammation (CSF WBC, CSF protein) by quartiles
- CRP at study entry by quartiles; by log2 transformation as continuous variable
- CD4 < 50 cells/mcL at study entry vs. >50 cells/mcL
- CD4 at entry by quartiles
- HIV-1 viral load at entry
- Renal function (calculated creatinine clearance) at study entry by quartiles
- Receiving TB treatment at entry
- ART regimen initially prescribed (documented pre-randomization).
- Duration/dose of amphotericin 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: Early HIV Therapy
HIV therapy initiated within 48 hours after study entry (at 7-11 days of cryptococcal treatment)
|
Other: Early HIV Therapy Initiation
Treatment strategy of when to initiate first line HIV therapy
Other Name: HIV
|
Active Comparator: Standard HIV Therapy
HIV therapy initiated at >=4 weeks after study entry (at 7-11 days of cryptococcal meningitis treatment), per the usual standard of care
|
Other: Active Comparer Standard HIV Therapy Initiation
Treatment strategy of when to initiate first line HIV therapy
Other Name: HIV Drugs
|
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
Ages Eligible for Study: | 14 Years and older |
Genders Eligible for Study: | Both |
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
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
University of Cape Town
Investigators
Principal Investigator: | David R Boulware, MD, MPH | University of Minnesota - Clinical and Translational Science Institute |
More Information
Additional Information:
No publications provided
Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 10, 2013
Additional Information:
No publications provided
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: | March 4, 2013 |
Health Authority: | United States: Institutional Review Board United States: Federal Government Uganda: National Council for Science and Technology South Africa: Human Research Ethics Committee |
Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
cryptococcal meningitis cryptococcus cryptococcosis |
HIV AIDS strategy |
Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome HIV Infections Meningitis Meningitis, Cryptococcal Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases |
Slow Virus Diseases Immunologic Deficiency Syndromes Immune System Diseases Central Nervous System Infections Central Nervous System Diseases Nervous System Diseases Meningitis, Fungal Central Nervous System Fungal Infections Mycoses Cryptococcosis |
ClinicalTrials.gov processed this record on March 10, 2013