ACACIA: Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

Sponsor

Makerere University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03945448

Collaborator

University of Minnesota (Other), Gilead Sciences (Industry)

600

Enrollment

Location

Arms

52.4

Anticipated Duration (Months)

11.4

Patients Per Site Per Month

Study Details

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.

Survival will also be evaluated by CrAg titer (comparing high titers who received Liposomal Amphotericin B (L-AMB) to high titers who received fluconazole alone), safety, tolerability, and cost-effectiveness of this regimen.

600 patients will be enrolled,300 in each arm.

Condition or Disease	Intervention/Treatment	Phase
Cryptococcal Meningitis	Drug: Single dose liposomal Amphotericin and Fluconazole Drug: Fluconazole	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 20, 2019

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single dose liposomal Amphotericin and fluconazole 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)	Drug: Single dose liposomal Amphotericin and Fluconazole Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months. Other Names: AMBISOME and fluconazole
Active Comparator: fluconazole (standard of care) Standard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months	Drug: Fluconazole Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months

Arm

Intervention/Treatment

Experimental: Single dose liposomal Amphotericin and fluconazole

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)

Drug: Single dose liposomal Amphotericin and Fluconazole

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

Other Names:

AMBISOME and fluconazole

Active Comparator: fluconazole (standard of care)

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

Drug: Fluconazole

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

Outcome Measures

Primary Outcome Measures

Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm. [24 weeks]
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 [within two weeks of enrollment]
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 [within two weeks of enrollment]
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. [24 weeks]
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. [24 weeks]
How many patients will be alive at 24 weeks when the two arms are compared.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

HIV-1 infection
Age >18 years
Ability and willingness to give informed consent.
Plasma/Serum cryptococcal antigen (CRAG)+

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	infectious Disease Institute Kampala,Uganda	Kampala		Uganda

Sponsors and Collaborators

Makerere University
University of Minnesota
Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Oct 13, 2021

More Information

Publications

None provided.

Responsible Party:

Makerere University

ClinicalTrials.gov Identifier:

NCT03945448

Other Study ID Numbers:

ST/225/2018

First Posted:

May 10, 2019

Last Update Posted:

Dec 16, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Meningitis, Cryptococcal

Meningitis

Fluconazole

Amphotericin B

Liposomal amphotericin B

Study Results

No Results Posted as of Dec 16, 2021