The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is ending enrollment in its "Cryptococcal Optimal ART Timing" (COAT) study because of higher mortality rates among participants in one of the two HIV treatment arms.
The Phase IV study began in November 2010. It was evaluating whether HIV-infected participants hospitalized with cryptococcal meningitis (CM) but not yet taking antiretroviral therapy (ART) would improve their chances of survival if they began ART while receiving CM treatment as inpatients compared with the standard practice of beginning ART as outpatients, approximately five weeks after receiving CM treatment.
Two reviews of the COAT trial's safety and effectiveness data last month by an independent data and safety monitoring board (DSMB) found substaintially higher mortality rates among the 87 participants who received early ART compared with the 87 participants who received delayed HIV treatment. For this reason, the DSMB recommended that study enrollment end immediately. As the study's sponsor, NIAID agreed with the DSMB's recommendation.
Cryptococcal meningitis is a fungal infection of the brain and spinal cord that annually occurs in an estimated 1 million people worldwide, killing roughly 600,000. It primarily affects people with weakened immune systems, including individuals infected with HIV. In Sub-Saharan Africa, cryptococcal meningitis is a leading cause of death among individuals with HIV/AIDS.
The COAT study, which was being conducted at two sites in Uganda and one in South Africa, was intended to enroll 500 volunteers ages 14 years and older diagnosed with CM and HIV but not yet taking ART to treat HIV. Cryptococcal meningitis treatment consisted of 14 days of the anti-fungal drug amphotericin B followed by fluconazole. Antiretroviral therapy included an efavirenz-based regimen in accordance with national treatment guidelines, The study was slated to end in June 2015.
Participants are being notified of the study's developments and will continue to be followed by study staff. Treating clinicians are being advised to continue or modify ART for current study participants based on standard of care and medical judgment.
The COAT trial was initiated and is being coordinated by the University of Minnesota's Clinical and Translational Science Institute in collaboration with NIAID; Mbarara University of Science and Technology-Uganda; the Infectious Diseases Institute/Makerere University-Uganda; and the University of Cape Town-South Africa. The ClinicalTrials.gov identifier for the COAT Trial is NCT01075152.