High Dose AMBISOME on a Fluconazole Backbone for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa:
A Phase 3 Randomised Controlled Non-Inferiority Trial
This ongoing multi-centre clinical trial (ISRCTN72509687), sponsored by the London School of Hygiene & Tropical Medicine (LSHTM) is an open label phase III randomised controlled non-inferiority trial to compare single high dose L-AmB (Liposomal Amphotericin B – Ambisome®) therapy to the newly WHO-recommended 7-day Amphotericin B deoxycholate based therapy 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 recently recommended 1-week daily-dosed Amphotericin B deoxycholate based induction therapy with flucytosine, in terms of preventing deaths from HIV-associated cryptococcal meningitis. This trial is the largest therapeutic trial on cryptococcal meningitis with 850 patients to be enrolled over a 3-year period.
Patients are being enrolled in the following study sites:
– Princess Marina Hospital (Gaborone, Botswana)
– Mitchells Plain District Hospital (Cape Town, South Africa)
– Parirenyatwa Central Hospital (Harare, Zimbabwe)
– Queen Elizabeth Central Hospital (Blantyre, Malawi)
– Kamuzu Central Hospital (Lilongwe, Malawi)
– Mulago Hospital, Infectious Disease Institute (Kampala, Uganda)
– Mbarara Hospital (Mbarara, Uganda)
The members of the Molecular Mycology Unit involved in the project will:
- provide senior scientific leadership of the overall project, supporting the Clinical Lead and Trial Manager at LSHTM with overall coordination and management of the project
- 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;
- provide 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.
In collaboration with the University of Aberdeen and the AFGrica Unit at University of Cape Town, the Molecular Mycology Unit team has organised the AMBITION-cm Medical Mycology Course in Africa, which took place from 10th – 14th December 2018 in Cape Town, South Africa.