A phase III, randomised, controlled trial for the treatment of HIV-associated cryptococcal meningitis: oral fluconazole plus flucytosine or one week amphotericin B-based therapy vs two weeks amphotericin B-based therapy

Conditions

HIV-associated cryptococcal meningitis Infections and Infestations Cryptococcosis, unspecified

Samuels THA, Molloy SF, Lawrence DS, Loyse A, Kanyama C, Heyderman RS, Lai WS, Mfinanga S, Lesikari S, Chanda D, Kouanfack C, Temfack E, Lortholary O, Hosseinipour MC, Chan AK, Meya DB, Boulware DR, Mwandumba HC, Meintjes G, Muzoora C, Mosepele M, Ndhlovu CE, Youssouf N, Harrison TS, Jarvis JN, Gupta RK.

2025-05-013 citations

10.1016/s2214-109x(25)00010-5

Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa

Tao Chen, Lawrence Mwenge, Shabir Lakhi, Duncan Chanda, Peter Mwaba et al. (22 authors)

Clinical Infectious Diseases2018-11-2523 citations

10.1093/cid/ciy971

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa

Síle F. Molloy, Cecilia Kanyama, Robert S. Heyderman, Angela Loyse, Charles Kouanfack et al. (37 authors)

New England Journal of Medicine2018-03-14392 citations

10.1056/nejmoa1710922

Interventions

Study Regimen 1: Fluconazole 1200 mg /d plus Flucytosine 25 mg/kg four times a day (qds) for 2 weeks Study Regimen 2: Amphotericin B (AmB) 1 mg/kg/d plus EITHER 2A: fluconazole 1200 mg /d, OR 2B:

Eligibility

Sex/Gender

All

Age

18 Years to 110 Years

Inclusion criteria

Inclusion criteria: Current inclusion criteria as of 21/10/2013: 1. Consecutive patients age 18 years or over with a first episode of cryptococcal meningitis on basis cerebrospinal fluid (CSF) India ink and/or CSF cryptococcal antigen. 2. Willing to agree to HIV testing 3. Willing to consent to participate in the study. Previous inclusion criteria: 1. Consecutive patients age > 18 years with a first episode of cryptococcal meningitis on basis cerebrospinal fluid (CSF) India ink and/or CSF cryptococcal antigen 2. Willing to agree to HIV testing 3. Willing to consent to participate in the study

Exclusion criteria

Exclusion criteria: Current exclusion criteria as of 15/12/2014: 1. Pregnancy or lactation 2. Previous serious reaction to study drugs 3. Concomitant medication that is contraindicated with any study drugs 4. Received >1 dose of Amphotericin B therapy within 2 weeks of screening 5. Received > 1 cryptococcal treatment dose (up to 1200 mg) of fluconazole or > 7 days low dose (200 mg) fluconazole within 2 weeks of screening Previous exclusion criteria from 21/10/2013 to 15/12/2014: 1. Pregnancy or lactation. 2. Previous serious reaction to study drugs 3. Concomitant medication that is contraindicated with any study drugs. 4. Received >1 dose of amphotericin B or fluconazole therapy within 2 weeks of screening Original exclusion criteria: 1. Pregnancy or lactation 2. Previous serious reaction to study drugs 3. Concomitant medication that is contraindicated with any study drugs 4. Already on anti-retroviral therapy (ART)

Design outcomes

Primary

Measure	Time frame
Mortality at 2 weeks by treatment group (regimen 1 and regimen 2 vs regimen 3)	—

Secondary

Measure	Time frame
1. Mortality at 10 weeks by treatment group, as above 2. Mortality at 2, 10 weeks by treatment group (regimens [2A + 3A] vs regimens [2B + 3B]; and 2A vs 2B, 3A vs 3B) 3. Mortality at 2, 4, and 10 weeks by treatment group, as above, adjusted for site and other possible confounders. 4. The proportion of patients in each arm suffering clinical and laboratory-defined adverse events 5. Rate of clearance of infection by treatment group based on cerebrospinal fluid (CSF) quantitative cultures at baseline and days 7 and 14 6. The proportion of patients in each arm suffering pre-defined Immune reconstitution inflammatory syndrome (IRIS) reactions to 10 weeks	—

Measure

Time frame

1. Mortality at 10 weeks by treatment group, as above 2. Mortality at 2, 10 weeks by treatment group (regimens [2A + 3A] vs regimens [2B + 3B]; and 2A vs 2B, 3A vs 3B) 3. Mortality at 2, 4, and 10 weeks by treatment group, as above, adjusted for site and other possible confounders. 4. The proportion of patients in each arm suffering clinical and laboratory-defined adverse events 5. Rate of clearance of infection by treatment group based on cerebrospinal fluid (CSF) quantitative cultures at baseline and days 7 and 14 6. The proportion of patients in each arm suffering pre-defined Immune reconstitution inflammatory syndrome (IRIS) reactions to 10 weeks

—

Countries

Cameroon, England, Malawi, Tanzania, United Kingdom, Zambia

Outcome results

None listed