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
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
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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 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:
- Mortality [ Time Frame: 26 weeks from study entry ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
- Incidence of Cryptococcal-relapse [ Time Frame: 46 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, 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 ] [ 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
- Karnofsky Functional Status [ Time Frame: 46 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 Names:
|
|
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 Names:
|
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 (Child, Adult, Senior) |
| 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
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
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
Additional Information:
Publications:
| 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 |
| Results First Received: | June 27, 2014 |
| Last Updated: | August 13, 2015 |
| 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:
|
HIV Infections Meningitis Meningitis, Cryptococcal Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Central Nervous System Diseases Nervous System Diseases Meningitis, Fungal Central Nervous System Fungal Infections |
Mycoses Cryptococcosis Central Nervous System Infections Lamivudine Efavirenz Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-HIV Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors |
ClinicalTrials.gov processed this record on September 28, 2016