AMBITION-cm: AMBIsome Therapy Induction OptimizatioN - Intermittent high dose AmBisome® on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa

Intermittent high dose AmBisome® on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: An adaptive randomized controlled non-inferiority trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN10248064

Enrollment

1010

Registered

2014-01-22

Start date

2014-11-01

Completion date

Unknown

Last updated

2021-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV-associated cryptococcal meningitis Infections and Infestations Human immunodeficiency virus [HIV] disease resulting in other conditions

Interventions

Current interventions as of 24/10/2017: A trial to compare alternative short course AmBisome® (amphotericin) regimens for the treatment of HIV-associated cryptococcal meningitis.

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Consecutive patients (male and female) aged > 18 years with a first episode of cryptococcal meningitis (CSF India ink or CrAg test) 2. Known to be HIV positive or willing to undertake an HIV test 3. Willing to agree to participate in the study

Exclusion criteria

Exclusion criteria: 1. Pregnancy or lactation 2. Previous serious reaction to study drugs 3. Already taking antifungals for >48 hours 4. Concomitant medication that is contraindicated with study drugs

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 24/10/2017: STEP 1: Early Fungicidal Activity (EFA) in the first 2 weeks of treatment STEP 2: all-cause mortality within the first 10 weeks after randomization (non-inferiority) Previous primary outcome measures: STEP 1: Early Fungicidal Activity (EFA) in the first 2 weeks of treatment STEP 2: All-cause mortality in the first 14 and 70 days after randomization	—

Measure

Time frame

Current primary outcome measures as of 24/10/2017: STEP 1: Early Fungicidal Activity (EFA) in the first 2 weeks of treatment STEP 2: all-cause mortality within the first 10 weeks after randomization (non-inferiority) Previous primary outcome measures: STEP 1: Early Fungicidal Activity (EFA) in the first 2 weeks of treatment STEP 2: All-cause mortality in the first 14 and 70 days after randomization

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Secondary

Measure	Time frame
Current secondary outcome meaures as of 24/10/2017: Step 1: 1. Pharmacokinetic (PK) parameters and Pharmacokinetic/Pharmacodynamic (PK/PD) associations of alternative schedules of intermittent high dose Ambisome. 2. Proportion of patients in each arm suffering clinical and laboratory-defined grade iii/iv adverse events; median % change from baseline in laboratory-defined parameters by treatment arm. 3. Health service costs by treatment arm. Step2: 1. Early Fungicidal Activity 2. Proportions of patients developing clinical and laboratory-defined grade III/IV adverse events; median % change from baseline in laboratory defined parameters 3. PK parameters and PK/PD associations 4. Health service costs by treatment arm 5. All-cause mortality within the first 2 and 4 weeks 6. All-cause mortality within the first 10 weeks (superiority) 7. Rates of cryptococcal relapse / IRIS within the first 10 weeks 8. Disability at 10 weeks Previous secondary outcome measures: 1. Pharmacokinetic (PK) parameters and Pharmacokinetic/Pharmacodynamic (PK/PD) associations of alternative schedules of intermittent high dose Ambisome. 2. Proportion of patients in each arm suffering clinical and laboratory-defined grade iii/iv adverse events; median % change from baseline in laboratory-defined parameters by treatment arm. 3. Health service costs by treatment arm.	—

Measure

Time frame

Current secondary outcome meaures as of 24/10/2017: Step 1: 1. Pharmacokinetic (PK) parameters and Pharmacokinetic/Pharmacodynamic (PK/PD) associations of alternative schedules of intermittent high dose Ambisome. 2. Proportion of patients in each arm suffering clinical and laboratory-defined grade iii/iv adverse events; median % change from baseline in laboratory-defined parameters by treatment arm. 3. Health service costs by treatment arm. Step2: 1. Early Fungicidal Activity 2. Proportions of patients developing clinical and laboratory-defined grade III/IV adverse events; median % change from baseline in laboratory defined parameters 3. PK parameters and PK/PD associations 4. Health service costs by treatment arm 5. All-cause mortality within the first 2 and 4 weeks 6. All-cause mortality within the first 10 weeks (superiority) 7. Rates of cryptococcal relapse / IRIS within the first 10 weeks 8. Disability at 10 weeks Previous secondary outcome measures: 1. Pharmacokinetic (PK) parameters and Pharmacokinetic/Pharmacodynamic (PK/PD) associations of alternative schedules of intermittent high dose Ambisome. 2. Proportion of patients in each arm suffering clinical and laboratory-defined grade iii/iv adverse events; median % change from baseline in laboratory-defined parameters by treatment arm. 3. Health service costs by treatment arm.

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Countries

Botswana, South Africa, Tanzania, Zimbabwe

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Mar 17, 2026