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Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia (ACACIA)

Primary Purpose

Cryptococcal Meningitis

Status

Recruiting

Phase

Phase 2

Locations

Uganda

Study Type

Interventional

Intervention

Single dose liposomal Amphotericin and Fluconazole

Fluconazole

About this trial

This is an interventional prevention trial for Cryptococcal Meningitis

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

HIV-1 infection
Age >18 years
Ability and willingness to give informed consent.
Plasma/Serum cryptococcal antigen (CRAG)+ with a titer 1:160 or greater

Exclusion Criteria:

Cannot or unlikely to attend regular clinic visits
History of cryptococcal infection
Symptomatic meningitis (confirmed by CSF CRAG+)
>14 days of fluconazole therapy
Pregnancy (confirmed by urinary or serum pregnancy test)
Current breastfeeding
Known allergy to amphotericin

Sites / Locations

infectious Disease Institute Kampala,UgandaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Single dose liposomal Amphotericin and fluconazole

fluconazole (standard of care)

Arm Description

Experimental: Single dose Ambisome 10mg/kg and Fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months. (standard of care therapy)

Standard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months

Outcomes

Primary Outcome Measures

Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm.

Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone

Secondary Outcome Measures

Number of grade 3 to 5 clinical adverse events or serious adverse events

Symptoms causing inability to perform social and functional activities and potentially life threatening symptoms requiring intervention or hospitalization.

Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale

Abnormal laboratory findings that meet the DAIDS categorization of grade 3 and 4.

Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy.

what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes.

Number of patients that will survive in the 24-week period.

How many patients will be alive at 24 weeks when the two arms are compared.

Full Information

NCT ID

NCT03945448

First Posted

March 12, 2019

Last Updated

April 11, 2023

Sponsor

Makerere University

Collaborators

University of Minnesota, Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03945448

Brief Title

Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

Acronym

ACACIA

Official Title

Evaluation of CrAg Screening With Enhanced Antifungal Therapy for Asymptomatic CrAg+ Persons

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 20, 2019 (Actual)

Primary Completion Date

October 2027 (Anticipated)

Study Completion Date

April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Makerere University

Collaborators

University of Minnesota, Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda. Patients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg/kg) in addition to standard of care fluconazole therapy. How the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cryptococcal Meningitis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

356 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single dose liposomal Amphotericin and fluconazole

Arm Type

Experimental

Arm Description

Experimental: Single dose Ambisome 10mg/kg and Fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months. (standard of care therapy)

Arm Title

fluconazole (standard of care)

Arm Type

Active Comparator

Arm Description

Standard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months

Intervention Type

Drug

Intervention Name(s)

Single dose liposomal Amphotericin and Fluconazole

Other Intervention Name(s)

AMBISOME and fluconazole

Intervention Description

Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months.

Intervention Type

Drug

Intervention Name(s)

Fluconazole

Intervention Description

Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months

Primary Outcome Measure Information:

Title

Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm.

Description

Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Number of grade 3 to 5 clinical adverse events or serious adverse events

Description

Symptoms causing inability to perform social and functional activities and potentially life threatening symptoms requiring intervention or hospitalization.

Time Frame

within two weeks of enrollment

Title

Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale

Description

Abnormal laboratory findings that meet the DAIDS categorization of grade 3 and 4.

Time Frame

within two weeks of enrollment

Title

Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy.

Description

what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes.

Time Frame

24 weeks

Title

Number of patients that will survive in the 24-week period.

Description

How many patients will be alive at 24 weeks when the two arms are compared.

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HIV-1 infection Age > or equal to15 years Ability and willingness to give informed consent. Plasma/Serum cryptococcal antigen (CRAG)+ with a titer 1:160 or greater Exclusion Criteria: Cannot or unlikely to attend regular clinic visits History of cryptococcal infection Symptomatic meningitis (confirmed by CSF CRAG+) >14 days of fluconazole therapy Pregnancy (confirmed by urinary or serum pregnancy test) Current breastfeeding Known allergy to amphotericin

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

DAVID MEYA, PhD

Phone

+256 772 543 730

david.meya@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

ELIZABETH NALINTYA, MPH

Phone

+256 771 321 617

enalintya@idi.co.ug

Facility Information:

Facility Name

infectious Disease Institute Kampala,Uganda

City

Kampala

Country

Uganda

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

DAVID MEYA, PhD

Phone

+256 772 543 730

david.meya@gmail.com

First Name & Middle Initial & Last Name & Degree

ELIZABETH NALINTYA, MPH

Phone

+256 771 321 617

enalintya@idi.co.ug

First Name & Middle Initial & Last Name & Degree

DAVID MEYA, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

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