Cryptococcal Optimal ART Timing Trial (COAT)

University of Minnesota (UMN)

Status and phase: Completed; Phase 4

Conditions: AIDS; HIV Infections; Cryptococcal Meningitis

Treatments: Biological: nucleoside; Drug: efavirenz

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01075152

0810M49622

U01AI089244 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 177 patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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177 participants in 2 patient groups

Earlier HIV Therapy

Experimental group

Description:

HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.

Treatment:

Drug: efavirenz

Biological: nucleoside

Deferred HIV Therapy

Active Comparator group

Description:

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

Treatment:

Drug: efavirenz

Biological: nucleoside