NCT04140461

Brief Summary

Cryptococcal meningitis (CM) is one of the leading opportunistic infections and one of the most common causes of death in AIDS patients. Amphotericin B (AmB) is the corner stone in CM treatment. The effect of AmB was dose-dependent. Recent retrospective study indicated that longer duration rather than higher dose of AmB is necessary to reduce the mortality of CM. We aimed to explore the efficacy and safety of small dose but longer duration of AmB for the treatment of HIV-associated CM.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2020

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 24, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 25, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

January 2, 2020

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2022

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2022

Completed
Last Updated

October 29, 2019

Status Verified

October 1, 2019

Enrollment Period

2.2 years

First QC Date

October 24, 2019

Last Update Submit

October 25, 2019

Conditions

Keywords

HIV infectionCryptococcal MeningitisAmphotericin B

Outcome Measures

Primary Outcomes (1)

  • Number of subjects died at weeks 48

    Mortality in intent to treat population

    48 weeks after randomization

Secondary Outcomes (2)

  • Number of subjects with CSF culture positive for Cryptococcus at weeks 2

    2 weeks after randomization

  • Number of subjects with disability at weeks 48

    48 weeks after randomization

Other Outcomes (1)

  • Treatment-Emergent Adverse Events

    12 weeks after randomization

Study Arms (2)

Trial

EXPERIMENTAL

Amphotericin B 0.5 mg/kg IVGTT QD + Flucytosine 100mg/kg PO QD for 4 weeks

Drug: Amphotericin BDrug: Flucytosine

Control

ACTIVE COMPARATOR

Amphotericin B 0.7 mg/kg IVGTT QD + Flucytosine 100mg/kg PO QD for 2 weeks

Drug: Amphotericin BDrug: Flucytosine

Interventions

The trial group and the control group received AmB 0.5mg/kg for 4 weeks and 0.7mg/kg for 2 weeks respectively.

Also known as: Antiretroviral therapy
ControlTrial

The trial group and the control group received 100mg/kg for 4 weeks and for 2 weeks respectively.

ControlTrial

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed HIV infection
  • Naive to antiretroviral therapy
  • Cryptococcal antigen, smear or culture positive in cerebrospinal fluid
  • Agree to participate the study

You may not qualify if:

  • Having receiving antifungal treatment for ≥3 days
  • ALT or AST \> 5\* upper limit of detection (ULD), or neutrophil\< 0.5\*10E9 cells/L, or hemoglobin \< 90g/L or platelet \<50\*10E9/L or serum creatinine \> ULD
  • Pregnancy or breastfeeding
  • Concomitant medications that are contraindicated with any research drug
  • Any other contraindications for using amphotericin B or 5FC
  • Inability to follow-up as accessed by the investigator

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 201508, China

Location

MeSH Terms

Conditions

Meningitis, CryptococcalHIV Infections

Interventions

Amphotericin BAntiretroviral Therapy, Highly ActiveFlucytosine

Condition Hierarchy (Ancestors)

Meningitis, FungalCentral Nervous System Fungal InfectionsMycosesBacterial Infections and MycosesInfectionsCryptococcosisCentral Nervous System InfectionsCentral Nervous System DiseasesNervous System DiseasesMeningitisNeuroinflammatory DiseasesBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesPolyketidesLactonesOrganic ChemicalsDrug Therapy, CombinationDrug TherapyTherapeuticsCytosinePyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant of the department

Study Record Dates

First Submitted

October 24, 2019

First Posted

October 25, 2019

Study Start

January 2, 2020

Primary Completion

March 30, 2022

Study Completion

April 30, 2022

Last Updated

October 29, 2019

Record last verified: 2019-10

Locations