This multi-centre clinical trial, sponsored by the London School of Hygiene & Tropical Medicine (LSHTM) is an open label phase III randomised controlled non-inferiority trial to compare single dose L-AmB (Ambisome®) treatment to standard 14-day Amphotericin B deoxycholate based treatment for HIV-associated cryptococcal meningitis.
The aim is to find out whether a single high dose (10 mg/kg) of L-AmB given with high dose fluconazole and flucytosine is as effective as the standard 2 weeks daily-dosed Amphotericin B deoxycholate based induction therapy with flucytosine, in terms of preventing deaths from HIV-associated cryptococcal meningitis. This trial will be the largest therapeutic trial on cryptococcal meningitis with 850 patients to be enrolled over a 3-year period. Patients will be enrolled in the following study sites :
1. Princess Marina Hospital (Botswana)
2. Mitchells Plain District Hospital (South Africa)
3. Khayelitsha Hospital (South Africa)
4. Parirenyatwa Central Hospital (Zimbabwe)
5. Harare Central Hospital (Zimbabwe)
6. Queen Elizabeth Central Hospital (Malawi)
7. Kamuzu Central Hospital (Malawi)
8. Mulago Hospital, Infectious Disease Institute (Uganda)
9. Mbarara Hospital (Uganda)
The members of the Molecular Mycology Unit involved in the project will:
- provide senior scientific leadership of the overall project, supporting the the Clinical Lead and Trial Manager at LSHTM with overall coordination and management of the project;
- provide training and capacity building activities through short-course training in medical mycology in Africa, and providing a PhD level post to complete doctoral level training in medical mycology or a topic relevant to the Ambition project aims for an African investigator;
- contribute to the intellectual development of scientific sub-studies examining the contribution of host and pathogen genetic variation to CM outcome, exploring the immune correlates of clinical and mycological outcomes, and determining any association between baseline CrAg titre as assessed by a novel semi-quantitative POC CrAg test and response to treatment in each arm.