Trial Outcomes & Findings for Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal Meningitis (NCT NCT06414512)
NCT ID: NCT06414512
Last Updated: 2025-08-27
Results Overview
Rate of clearance of Cryptococcus from CSF.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
48 participants
Primary outcome timeframe
2 weeks
Results posted on
2025-08-27
Participant Flow
Controls were data drawn from another trial, not enrolled in this trial directly.
Participant milestones
| Measure |
Control
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
Overall Study
STARTED
|
171
|
48
|
|
Overall Study
COMPLETED
|
171
|
47
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Control
n=171 Participants
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=48 Participants
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
Total
n=219 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36 years
n=171 Participants
|
40 years
n=48 Participants
|
37 years
n=219 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=171 Participants
|
26 Participants
n=48 Participants
|
96 Participants
n=219 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=171 Participants
|
22 Participants
n=48 Participants
|
123 Participants
n=219 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: The number analyzed are lower because not all enrolled had data for these outcomes.
Rate of clearance of Cryptococcus from CSF.
Outcome measures
| Measure |
Control
n=97 Participants
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=44 Participants
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
Early Fungicidal Activity
|
0.39 log10 CFU/mL/day
Standard Deviation 0.27
|
0.28 log10 CFU/mL/day
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: 18 weeksPopulation: The number analyzed are lower because not all enrolled had data for these outcomes.
Cryptococcus is cleared or not from the cerebrospinal fluid
Outcome measures
| Measure |
Control
n=97 Participants
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=44 Participants
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
CSF Culture Sterility
|
60 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: 16 weeksThe proportion of participants who died after 16 weeks follow up
Outcome measures
| Measure |
Control
n=171 Participants
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=48 Participants
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
Mortality
|
50 Participants
|
11 Participants
|
Adverse Events
Control
Serious events: 132 serious events
Other events: 87 other events
Deaths: 50 deaths
Low Dose Flucytosine
Serious events: 31 serious events
Other events: 25 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Control
n=171 participants at risk
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=48 participants at risk
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/171 • 16 weeks
|
6.2%
3/48 • Number of events 3 • 16 weeks
|
|
Renal and urinary disorders
Acute Kidney Injury
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
8.3%
4/48 • Number of events 4 • 16 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
2.9%
5/171 • Number of events 5 • 16 weeks
|
4.2%
2/48 • Number of events 2 • 16 weeks
|
|
Metabolism and nutrition disorders
Metabolic Encephalopathy
|
0.00%
0/171 • 16 weeks
|
6.2%
3/48 • Number of events 3 • 16 weeks
|
|
Infections and infestations
Paradoxical CM IRIS
|
2.3%
4/171 • Number of events 4 • 16 weeks
|
8.3%
4/48 • Number of events 4 • 16 weeks
|
|
Nervous system disorders
Generalized tonic-clonic seizures
|
0.00%
0/171 • 16 weeks
|
4.2%
2/48 • Number of events 2 • 16 weeks
|
|
General disorders
Other
|
0.00%
0/171 • 16 weeks
|
6.2%
3/48 • Number of events 3 • 16 weeks
|
|
Infections and infestations
CM Relapse
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
12.5%
6/48 • Number of events 6 • 16 weeks
|
|
Infections and infestations
URI Bronchitis/ Sinusitis
|
0.00%
0/171 • 16 weeks
|
2.1%
1/48 • Number of events 1 • 16 weeks
|
|
Infections and infestations
Likely CM Persistence
|
0.00%
0/171 • 16 weeks
|
2.1%
1/48 • Number of events 1 • 16 weeks
|
|
Nervous system disorders
CNS Mass
|
0.00%
0/171 • 16 weeks
|
4.2%
2/48 • Number of events 2 • 16 weeks
|
|
Hepatobiliary disorders
Drug Induced Liver Injury
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Hepatobiliary disorders
Elevated Liver Enzymes
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.1%
7/171 • Number of events 7 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.1%
7/171 • Number of events 7 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Nervous system disorders
Abnormal Increase in CSF QCC
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Hepatobiliary disorders
Acute Cholecystitis
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Immune system disorders
Acute Hypersensitivity Reaction
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Infections and infestations
Bacteremia/ Sepsis
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
General disorders
Clinical Deterioration
|
1.8%
3/171 • Number of events 3 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
General disorders
Headache with Vomiting and Blurring
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
1.2%
2/171 • Number of events 2 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Nervous system disorders
Neurologic Deterioration
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Blood and lymphatic system disorders
Phlebitis
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.9%
5/171 • Number of events 5 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Surgical and medical procedures
Prolonged Hospitalization
|
8.8%
15/171 • Number of events 15 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Surgical and medical procedures
Readmission
|
14.6%
25/171 • Number of events 25 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Infections and infestations
Recurrence of Symptoms
|
1.8%
3/171 • Number of events 3 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
2.9%
5/171 • Number of events 5 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Infections and infestations
Severe scalp herpes zoster
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Infections and infestations
Tuberculosis
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Blood and lymphatic system disorders
Thrombophlebitis
|
0.58%
1/171 • Number of events 1 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
|
Investigations
Death, unknown cause
|
17.0%
29/171 • Number of events 29 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
Other adverse events
| Measure |
Control
n=171 participants at risk
Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received.
AMBITION trial control: Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days.
|
Low Dose Flucytosine
n=48 participants at risk
HIV-infected persons in Uganda with cryptococcal meningitis
Flucytosine: Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed.
|
|---|---|---|
|
Renal and urinary disorders
Creatinine Grade 3 or Worse
|
1.8%
3/171 • Number of events 3 • 16 weeks
|
2.1%
1/48 • Number of events 1 • 16 weeks
|
|
Blood and lymphatic system disorders
Hemoglobin Grade 3 or Worse
|
9.9%
17/171 • Number of events 17 • 16 weeks
|
14.6%
7/48 • Number of events 7 • 16 weeks
|
|
Hepatobiliary disorders
Elevated Liver Enzymes, Grade 3 or Worse
|
2.9%
5/171 • Number of events 5 • 16 weeks
|
6.2%
3/48 • Number of events 3 • 16 weeks
|
|
Metabolism and nutrition disorders
Potassium Grade 3 or worse
|
4.1%
7/171 • Number of events 7 • 16 weeks
|
2.1%
1/48 • Number of events 1 • 16 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia Grade 3 or worse
|
4.1%
7/171 • Number of events 7 • 16 weeks
|
2.1%
1/48 • Number of events 1 • 16 weeks
|
|
Blood and lymphatic system disorders
Leukopenia Grade 3 or worse
|
9.4%
16/171 • Number of events 16 • 16 weeks
|
10.4%
5/48 • Number of events 5 • 16 weeks
|
|
Blood and lymphatic system disorders
Neutropenia Grade 3 or worse
|
13.5%
23/171 • Number of events 23 • 16 weeks
|
14.6%
7/48 • Number of events 7 • 16 weeks
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
9/171 • Number of events 9 • 16 weeks
|
0.00%
0/48 • 16 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place