A Phase 1/2 interventional study of Fluconazole and Amphotericin B in Cryptococcal Meningitis and HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 10 sites in 8 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2021-11-04.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Treatment
Cryptococcal meningitis (CM) is an infection of the membranes covering the brain and spinal cord, caused by the fungus Cryptococcus neoformans. CM most often affects people with compromised immune systems, like those with advanced HIV infection. This study explored the safety, tolerability, and therapeutic effect of a new treatment regimen with high-dose fluconazole for management of CM in HIV-infected patients.
CM is the most common central nervous system (CNS) complication of AIDS worldwide and accounts for up to a third of all deaths from AIDS in many developing countries. Current treatments for CM are lacking in both effectiveness and accessibility, particularly in limited-resources settings. Conventional therapies utilizing an amphotericin B deoxycholate (ampho B)-based regimen require maintaining intravenous access (IV) and monitoring and treating any associated complications. The price to acquire ampho B can also be prohibitive to successful treatment. Cumulatively, a treatment course with ampho B is neither cost effective nor administratively efficient, leaving patients either untreated or inadequately treated with low-dose regimens of fluconazole alone.
Fluconazole is widely available, inexpensive, can be given orally, has a demonstrated safety profile over a broad range of doses, and has proven activity against the fungus that causes CM, Cryptococcus neoformans. All of these factors make fluconazole a potential treatment option for a wide range of people. However, at its present recommended dosage, fluconazole is only expected to be successful in 34% to 42% of patients. This rate is lower than regimens combining fluconazole with other treatments including flucytosine or ampho B.
The purpose of this study was to evaluate whether high-dose fluconazole is safe and effective for the treatment of CM for up to 10 weeks. This study also collected information about treating CM with ampho B (either alone or with another drug, either flucytosine or fluconazole).
For this study, 168 HIV-infected people with CM participated for a duration of 24 weeks. This study proceeded with 2 stages and each stage consisted of up to 4 steps. Participants could take part in only one stage of the study. Stage 1 measured the maximum tolerated dose (MTD) of fluconazole in participants. Stage 2 consisted of dose validation and safety monitoring.
In Stage 1, participants were randomly assigned to receive either fluconazole only or an ampho B-based regimen (a regimen that is either ampho B alone or ampho B in combination with 5-fluorocytosine or fluconazole, according to the local standard of care).Three doses of fluconazole were tested, and the MTD was found to be 2000 mg/day. The two higher doses of fluconazole tested in Stage 1 (1600 mg/day and 2000 mg/day doses) were tested further in Stage 2 of the study.
Participants enrolled in Stage 2 were randomly assigned to receive treatment with either fluconazole only (at one of the 2 doses (1600 mg/day or 2000 mg/day) found to be safe in Stage 1) or an ampho B-based regimen.
After randomization in Step 1, participants in both Stage 1 and Stage 2 could be enrolled in up to three additional steps. In Step 2, participants who were randomly assigned to receive the ampho B-based regimen and who were intolerant to the regimen (experienced a treatment limiting toxicity [TLT]) received fluconazole (400-800mg daily). Participants who received study-provided fluconazole in Step 1 or in Step 2 could be enrolled in Step 3 if they had a negative cerebrospinal fluid (CSF) culture. Participants in Step 3 received fluconazole (400mg daily) until Week 10. At Week 10, all participants were enrolled in Step 4 and received a daily dose of fluconazole of 200mg until the end of the study (Week 24). Participants in both stages beginning treatment with ampho B received daily ampho B intravenously for up to 2 weeks.
Before entering the study, potential participants attended a screening visit where they had CSF collected via lumbar puncture. HIV testing was also conducted, along with clinical assessments, and a health and medical history questionnaire. Participants had blood collection, an electrocardiogram (ECG), and a pregnancy test (if applicable) at that visit. Once accepted into the study, participants again answered questions about their health and medication history; had a complete physical exam, blood collection, HIV testing, neurological exam, lumbar puncture, and ECG; and may have had a pregnancy test (if applicable).
Study visits occurred during Weeks 1 (at Days 1, 4, and 7), 2, 4, 6, 8, 10, and 24, and extra visits could occur for individualized reasons. Total study duration was 24 weeks. Plasma, urine, serum, and CSF samples were collected from all participants and stored for possible future use.
Note on efficacy population versus safety population: After entering the study, participants had their CM diagnosis confirmed by testing of the CSF collected via lumbar puncture. Confirmation could take up to 2 weeks after study entry. Due to the mortality rate of CM, participants received treatment before CM diagnosis confirmation. Post-entry 12 participants either reported non-confirmatory baseline results making them ineligible. An additional 2 participants were found to be ineligible for the study but died prior to being found ineligible (one had non-confirmatory baseline results, one was on a disallowed medication) All participants (n=168) are included in the safety population. Participants who were ineligible after study entry were excluded from the efficacy population (n=16). The efficacy population had 154 participants. Outcomes will specify if the efficacy population is used instead of the safety population.
54 studies on the registry are indexed under Meningitis, Cryptococcal; 6 are open to participants now.
This study's enrollment of 168 is above the median of 143 across 35 interventional studies indexed under Meningitis, Cryptococcal.
Browse Meningitis, Cryptococcal studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria - Step 1
Exclusion Criteria - Step 1
Inclusion Criteria - Step 2
Exclusion Criteria - Step 2
Inclusion Criteria - Step 3
Exclusion Criteria - Step 3
Inclusion Criteria - Step 4
Exclusion Criteria - Step 4
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive Fluconazole 1200mg induction dose in Stage 1
Drug: Fluconazole
Participants receive Fluconazole 1600mg induction dose in Stage 1
Drug: Fluconazole
Participants receive Fluconazole 2000mg induction dose in Stage 1
Drug: Fluconazole
Participants receive Amphotericin B followed by Fluconazole in Stage 1
Drug: Fluconazole · Drug: Amphotericin B
Participants receive Fluconazole 1600mg induction dose in Stage 2
Drug: Fluconazole
Participants receive Fluconazole 2000mg induction dose in Stage 2
Drug: Fluconazole
Participants receive Amphotericin B followed by Fluconazole in Stage 2
Drug: Fluconazole · Drug: Amphotericin B
Step 1: \[For participants randomized to Fluconazole\] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: \[For participants randomized to Ampho B only\] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.
Also known as: Diflucan
Step 1: \[For participants randomized to Ampho B\] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight
Also known as: Amphotericin B deoxycholate, Ampho B, Amphocin, Fungizone, AmBisome, Abelecet, Amphotec
Number of Participants Who Discontinued Study-provided High Dose Fluconazole or Ampho B
Discontinuation of study-provided high dose fluconazole at or by week 10 Discontinuation of study-provided ampho B at or by week 2 Discontinuation includes discontinuing for any reason, including progression of symptoms, death, etc.
Time frame: Measured from study entry through Week10
Categorized Quantitative Culture Results
Count of participants who were CM negative (had no cryptococcal growth), CM negative after switching treatment (switched from Fluconazole to Ampho B or vice versa and later became CM negative), CM positive, Died, Lost to follow-up. Note: CM positive means continued to have cryptococcal growth.
Time frame: At entry, Week 2, and Week 10
Change in Log10 Quantitative CSF Culture Results
Change in quantitative CSF (cerebrospinal fluid) cultures. Note: No further CSF specimens are drawn following a negative culture. Thus, only week 2 CSF cultures are considered in this analysis.
Time frame: Entry and Week 2
Kaplan Meier (KM) Proportion of Participant Mortality
Kaplan Meier Proportion of participants who died over study with 90% Confidence Intervals.
Time frame: Measured from study entry through Week 24
Results of the Neurological Examination
Results from Glasgow Coma Score, which provides assessment of impairment of conscious level in response to defined stimuli. Min score of 0 and max score of 15 (no mental impairment).
Time frame: Measured at study entry, Week 2, and Week 10
Results of Functional Status Evaluation
Functional assessment of work status and ability. Consists of 2 measures: 1) Does participants have full time work status 2) Does participant have functional ability to work. The measure from 6 week before enrollment will be referred to as 'baseline'.
Time frame: Measured 6 weeks before enrollment, at study entry, at Week 10, and at Week 24
Length of Hospitalization
Duration of first hospitalization in days starting at entry in safety population.
Time frame: Measured from study entry through Week 10
Number of Hospital Admissions
Count of number of times a participant was admitted to the hospital.
Time frame: Measured from study entry through Week 24
Number of Participants With Progression of Symptoms
Progression of symptoms is defined as: * Died (including early deaths) * Discontinued Fluconazole and started ampho B * Had a positive cryptococcal culture at week 10 * Microbiological Failure (i.e., relapse of CM) * Complication of CM (e.g., obstructive hydrocephalus or vascular complications such as venous or arterial thrombosis) * CM IRIS causing increased inflammation after ART exposure * New CNS Ol (e.g., toxoplasmosis, PML, CNS lymphoma) * Possibly related to CM but mechanism indeterminate * Other defined complication unrelated to CM
Time frame: Measured from study entry through Week 24
Number of Participants With CNS IRIS
Number of participants who were diagnosed with CNS immune reconstitution inflammatory syndrome (IRIS)
Time frame: Measured from study entry through Week 24
Number of Participants With Grade 3 and 4 Adverse Events
Occurrence of grade 3 (severe) and 4 (life-threatening) sign and symptoms events (as defined by FSTRF Appendix 29) Occurrence of grade 3 (severe) and 4 (life-threatening) laboratory events (as defined by FSTRF Appendix 76) See DAIDS AE Grading table V1.0
Time frame: Measured from study entry through Week 24
The study opened on February 19, 2010. The first participant enrolled on April 16, 2010. Stage 1 closed on September 5, 2013. A5225 Stage 2 opened on September 15, 2014 and the first participant enrolled on February 2, 2015. Stage 2 closed on August 19, 2016. Ten sites enrolled participants (1 domestic, 9 international).
| Milestone | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fulconazole 2000mg | Stage 2, Ampho B |
|---|---|---|---|---|---|---|---|
| Started | 22 | 26 | 24 | 24 | 24 | 24 | 24 |
| Completed | 12 | 16 | 13 | 15 | 12 | 11 | 18 |
| Not completed | 10 | 10 | 11 | 9 | 12 | 13 | 6 |
| Withdrew: Death | 9 | 7 | 8 | 7 | 7 | 8 | 4 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 1 | 3 | 1 | 1 |
| Withdrew: Ineligible (no cm) | 1 | 3 | 2 | 1 | 2 | 3 | 1 |
Discontinuation of study-provided high dose fluconazole at or by week 10 Discontinuation of study-provided ampho B at or by week 2 Discontinuation includes discontinuing for any reason, including progression of symptoms, death, etc.
| Participants | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B |
|---|---|---|---|---|---|---|---|
| Number of Participants Who Discontinued Study-provided High Dose Fluconazole or Ampho B | 14 | 11 | 11 | 6 | 12 | 13 | 6 |
Count of participants who were CM negative (had no cryptococcal growth), CM negative after switching treatment (switched from Fluconazole to Ampho B or vice versa and later became CM negative), CM positive, Died, Lost to follow-up. Note: CM positive means continued to have cryptococcal growth.
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Week 0 — CM Positive | 20 | 45 | 43 | 46 |
| Week 0 — CM Negative | 0 | 0 | 0 | 0 |
| Week 0 — CM Negative after switching treatment | 0 | 0 | 0 | 0 |
| Week 0 — Died | 0 | 0 | 0 | 0 |
| Week 0 — Lost to Follow-up | 0 | 0 | 0 | 0 |
| Week 2 — CM Positive | 12 | 27 | 27 | 29 |
| Week 2 — CM Negative | 3 | 12 | 10 | 13 |
| Week 2 — CM Negative after switching treatment | 0 | 0 | 0 | 0 |
| Week 2 — Died | 5 | 6 | 6 | 4 |
| Week 2 — Lost to Follow-up | 0 | 0 | 0 | 0 |
| Week 10 — CM Positive | 3 | 4 | 3 | 2 |
| Week 10 — CM Negative | 8 | 24 | 22 | 37 |
| Week 10 — CM Negative after switching treatment | 1 | 4 | 5 | 1 |
| Week 10 — Died | 8 | 10 | 12 | 5 |
| Week 10 — Lost to Follow-up | 0 | 3 | 1 | 1 |
Change in quantitative CSF (cerebrospinal fluid) cultures. Note: No further CSF specimens are drawn following a negative culture. Thus, only week 2 CSF cultures are considered in this analysis.
| Log10 CFU/mL | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Change in Log10 Quantitative CSF Culture Results | -1.51 (-2.90 to -0.91) | -2.51 (-4.00 to -1.44) | -1.78 (-3.24 to -1.00) | -2.81 (-4.09 to -1.92) |
Kaplan Meier Proportion of participants who died over study with 90% Confidence Intervals.
| proportion of participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Kaplan Meier (KM) Proportion of Participant Mortality | 0.41 (0.26 to 0.60) | 0.30 (0.20 to 0.43) | 0.36 (0.25 to 0.49) | 0.24 (0.15 to 0.36) |
Results from Glasgow Coma Score, which provides assessment of impairment of conscious level in response to defined stimuli. Min score of 0 and max score of 15 (no mental impairment).
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Week 0 — Score < 15 | 5 | 5 | 5 | 1 |
| Week 0 — Score = 15 | 17 | 45 | 42 | 47 |
| Week 2 — Score < 15 | 2 | 4 | 4 | 5 |
| Week 2 — Score = 15 | 15 | 38 | 36 | 38 |
| Week 10 — Score < 15 | 1 | 1 | 1 | 0 |
| Week 10 — Score = 15 | 11 | 33 | 26 | 34 |
Functional assessment of work status and ability. Consists of 2 measures: 1) Does participants have full time work status 2) Does participant have functional ability to work. The measure from 6 week before enrollment will be referred to as 'baseline'.
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Baseline Had full time work status | 18 | 41 | 36 | 42 |
| Entry Had full time work status | 3 | 9 | 8 | 9 |
| Week 10 Had full time work status | 3 | 16 | 9 | 13 |
| Week 24 Had full time work status | 7 | 18 | 17 | 22 |
| Baseline Had functional ability to work | 16 | 41 | 32 | 38 |
| Entry Had functional ability to work | 1 | 8 | 3 | 7 |
| Week 10 Had functional ability to work | 4 | 18 | 9 | 15 |
| Week 24 Had functional ability to work | 7 | 19 | 16 | 24 |
Duration of first hospitalization in days starting at entry in safety population.
| Days | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Length of Hospitalization | 15 (10 to 21) | 17.5 (10 to 28) | 18 (13 to 36) | 18.5 (17 to 26) |
Count of number of times a participant was admitted to the hospital.
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| 1 hospital admission | 18 | 39 | 41 | 37 |
| 2 hospital admissions | 1 | 9 | 6 | 10 |
| 3 hospital admissions | 3 | 2 | 1 | 1 |
Progression of symptoms is defined as: * Died (including early deaths) * Discontinued Fluconazole and started ampho B * Had a positive cryptococcal culture at week 10 * Microbiological Failure (i.e., relapse of CM) * Complication of CM (e.g., obstructive hydrocephalus or vascular complications such as venous or arterial thrombosis) * CM IRIS causing increased inflammation after ART exposure * New CNS Ol (e.g., toxoplasmosis, PML, CNS lymphoma) * Possibly related to CM but mechanism indeterminate * Other defined complication unrelated to CM
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Number of Participants With Progression of Symptoms | 14 | 21 | 24 | 19 |
Number of participants who were diagnosed with CNS immune reconstitution inflammatory syndrome (IRIS)
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Number of Participants With CNS IRIS | 1 | 0 | 0 | 1 |
Occurrence of grade 3 (severe) and 4 (life-threatening) sign and symptoms events (as defined by FSTRF Appendix 29) Occurrence of grade 3 (severe) and 4 (life-threatening) laboratory events (as defined by FSTRF Appendix 76) See DAIDS AE Grading table V1.0
| Participants | Fluconazole 1200mg | Fluconazole 1600mg | Fluconazole 2000mg | Ampho B |
|---|---|---|---|---|
| Sign/Symptom Events | 16 | 23 | 32 | 24 |
| Laboratory Events | 12 | 27 | 26 | 30 |
Collected over Adverse event data were collected from study entry until end of study (24 weeks).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stage 1: 1200mg Fluconazole | 9/22 (40.9%) | 14/22 (63.6%) | 22/22 (100%) |
| Stage 1: 1600mg Fluconazole | 7/26 (26.9%) | 13/26 (50%) | 26/26 (100%) |
| Stage 1: 2000mg Fluconazole | 8/24 (33.3%) | 13/24 (54.2%) | 24/24 (100%) |
| Stage 1: Ampho B | 7/24 (29.2%) | 11/24 (45.8%) | 24/24 (100%) |
| Stage 2: 1600mg Fluconazole | 7/24 (29.2%) | 10/24 (41.7%) | 24/24 (100%) |
| Stage 2: 2000mg Fluconazole | 8/24 (33.3%) | 12/24 (50%) | 24/24 (100%) |
| Stage 2: Ampho B | 4/24 (16.7%) | 6/24 (25%) | 24/24 (100%) |
| Event | Stage 1: 1200mg Fluconazole | Stage 1: 1600mg Fluconazole | Stage 1: 2000mg Fluconazole | Stage 1: Ampho B | Stage 2: 1600mg Fluconazole | Stage 2: 2000mg Fluconazole | Stage 2: Ampho B |
|---|---|---|---|---|---|---|---|
| Meningitis cryptococcalInfections and infestations | 5/22 | 7/26 | 6/24 | 2/24 | 5/24 | 2/24 | 4/24 |
| PneumoniaInfections and infestations | 1/22 | 0/26 | 3/24 | 0/24 | 1/24 | 2/24 | 0/24 |
| Disseminated cryptococcosisInfections and infestations | 2/22 | 0/26 | 0/24 | 0/24 | 1/24 | 0/24 | 0/24 |
| Intracranial pressure increasedNervous system disorders | 2/22 | 0/26 | 0/24 | 0/24 | 0/24 | 1/24 | 0/24 |
| SeizureNervous system disorders | 2/22 | 2/26 | 1/24 | 0/24 | 0/24 | 1/24 | 0/24 |
| SepsisInfections and infestations | 0/22 | 1/26 | 1/24 | 2/24 | 0/24 | 0/24 | 0/24 |
| NeutropeniaBlood and lymphatic system disorders | 1/22 | 0/26 | 0/24 | 0/24 | 0/24 | 1/24 | 0/24 |
| Immune reconstitution inflammatory syndromeImmune system disorders | 1/22 | 0/26 | 0/24 | 0/24 | 0/24 | 0/24 | 1/24 |
| OverdoseInjury, poisoning and procedural complications | 1/22 | 0/26 | 0/24 | 0/24 | 0/24 | 0/24 | 0/24 |
| Subdural haematomaInjury, poisoning and procedural complications | 1/22 | 0/26 | 0/24 | 0/24 | 0/24 | 0/24 | 0/24 |
| Event | Stage 1: 1200mg Fluconazole | Stage 1: 1600mg Fluconazole | Stage 1: 2000mg Fluconazole | Stage 1: Ampho B | Stage 2: 1600mg Fluconazole | Stage 2: 2000mg Fluconazole | Stage 2: Ampho B |
|---|---|---|---|---|---|---|---|
| Blood sodium decreasedInvestigations | 19/22 | 21/26 | 21/24 | 20/24 | 18/24 | 18/24 | 22/24 |
| Blood albumin decreasedInvestigations | 19/22 | 18/26 | 18/24 | 19/24 | 19/24 | 17/24 | 21/24 |
| Haemoglobin decreasedInvestigations | 8/22 | 11/26 | 9/24 | 11/24 | 8/24 | 8/24 | 17/24 |
| Blood bicarbonate decreasedInvestigations | 4/22 | 9/26 | 16/24 | 6/24 | 10/24 | 14/24 | 10/24 |
| Blood potassium decreasedInvestigations | 14/22 | 7/26 | 10/24 | 13/24 | 6/24 | 9/24 | 13/24 |
| Neutrophil count decreasedInvestigations | 4/22 | 8/26 | 11/24 | 6/24 | 14/24 | 8/24 | 10/24 |
| Blood glucose increasedInvestigations | 12/22 | 7/26 | 9/24 | 7/24 | 6/24 | 8/24 | 8/24 |
| Blood creatinine increasedInvestigations | 5/22 | 4/26 | 8/24 | 12/24 | 7/24 | 5/24 | 13/24 |
| White blood cell count decreasedInvestigations | 5/22 | 3/26 | 6/24 | 6/24 | 12/24 | 6/24 | 6/24 |
| MalaiseGeneral disorders | 0/22 | 0/26 | 4/24 | 2/24 | 10/24 | 5/24 | 5/24 |
| Age, Continuous(years) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Median | 40.5 (36 to 47) | 33 (28 to 39) | 38 (31 to 48) | 35.5 (30 to 41) | 32.5 (29.5 to 35.5) | 33.5 (29 to 38) | 37.5 (34 to 40) | 36 (30 to 41) |
| Sex: Female, Male(Participants) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 10 | 14 | 14 | 11 | 10 | 10 | 9 | 78 |
| Male | 12 | 12 | 10 | 13 | 14 | 14 | 15 | 90 |
| Race/Ethnicity, Customized(Participants) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Black Non-Hispanic | 12 | 21 | 22 | 19 | 24 | 22 | 23 | 143 |
| Hispanic (regardless of Race) | 0 | 4 | 2 | 1 | 0 | 2 | 1 | 10 |
| Asian, Pacific Islander | 10 | 1 | 0 | 4 | 0 | 0 | 0 | 15 |
| Region of Enrollment(participants) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| United States | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 4 |
| South Africa | 1 | 6 | 3 | 5 | 2 | 3 | 6 | 26 |
| Uganda | 0 | 2 | 11 | 5 | 14 | 13 | 12 | 57 |
| Zimbabwe | 2 | 4 | 1 | 3 | 4 | 1 | 3 | 18 |
| Kenya | 8 | 9 | 7 | 6 | 4 | 6 | 2 | 42 |
| Thailand | 5 | 0 | 0 | 1 | 0 | 0 | 0 | 6 |
| Peru | 0 | 4 | 0 | 0 | 0 | 1 | 1 | 6 |
| India | 5 | 1 | 0 | 3 | 0 | 0 | 0 | 9 |
| Weight(kilograms) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Median | 46.5 (42.0 to 52.2) | 50.5 (44.0 to 65.0) | 51.9 (43.5 to 58.5) | 56.8 (47.5 to 64.1) | 49.8 (44.5 to 60.0) | 55.0 (51.6 to 59.1) | 52.5 (48.5 to 60.1) | 52.0 (44.7 to 59.3) |
| BMI (Body Mass Index)(kg/m^2) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Median | 17.2 (15.6 to 19.6) | 19.6 (17.3 to 21.8) | 18.3 (17.2 to 22.7) | 19.8 (16.3 to 24.3) | 18.7 (17.1 to 20.3) | 19.8 (18.6 to 22.5) | 19.6 (17.5 to 22.9) | 18.9 (16.9 to 21.9) |
| CD4+(Participants) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| < 50 cells/mm^3 | 15 | 10 | 17 | 17 | 20 | 16 | 17 | 112 |
| 50 - <100 cells/mm^3 | 6 | 9 | 4 | 4 | 3 | 5 | 5 | 36 |
| 100 - <200 cells/mm^3 | 1 | 4 | 3 | 2 | 0 | 3 | 2 | 15 |
| 200+ cells/mm^3 | 0 | 3 | 0 | 1 | 1 | 0 | 0 | 5 |
| HIV-1 RNA(log10(copies/mL)) | Stage 1, Fluconazole 1200mg | Stage 1, Fluconazole 1600mg | Stage 1, Fluconazole 2000mg | Stage 1, Ampho B | Stage 2, Fluconazole 1600mg | Stage 2, Fluconazole 2000mg | Stage 2, Ampho B | Total |
|---|---|---|---|---|---|---|---|---|
| Median | 5.3 (5.1 to 6.0) | 5.6 (5.1 to 5.8) | 5.5 (5.2 to 5.9) | 5.4 (5.2 to 5.7) | 5.2 (4.9 to 5.5) | 4.9 (2.8 to 5.4) | 4.6 (3.5 to 5.5) | 5.3 (4.7 to 5.7) |
11 further baseline measures are reported on the registry.
This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Fluconazole
National Institute of Allergy and Infectious Diseases (NIAID) →