Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM)

University of Minnesota (UMN)

Status and phase: Completed; Phase 3

Conditions: Fungal Meningitis; Cryptococcal Meningitis

Treatments: Drug: Sertraline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01802385

R01NS086312-01 (U.S. NIH Grant/Contract)

S4 0296-01

Details and patient eligibility

About

This is a phase III trial to determine whether adjunctive sertraline will lead to improved survival 18-week survival.

There was an initial phase I/II unmasked dose finding pharmacokinetic study of CSF concentrations in 172 persons conducted from August 2013 to August 2014. See NCT03002012.

Full description

This is a phase III randomized trial to evaluate whether sertraline when added to standard amphotericin-based therapy for cryptococcal meningitis, will lead to improved survival . Cryptococcal meningitis diagnosis will be made via CSF cryptococcal antigen (CRAG) at time of lumbar puncture (LP) with confirmation by CSF culture. After informed consent, subjects that meet eligibility requirements will be able to enter study. A non-randomized phase I dose-escalation study will first be conducted to help optimize dosing for a larger randomized phase II study.

Phase III Design: Subjects will be randomized to standard induction therapy with masked placebo or sertraline at 400mg/day. We will use a permutated block randomization in a 1:1 allocation (n=275 per arm). Total anticipated enrollment: 550 subjects.

Enrollment: 460 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cryptococcal meningitis diagnosed by CSF cryptococcal antigen (CRAG)
• HIV-1 infection
• Ability and willingness of the participant or legal guardian/representative to provide informed consent
• Willing to receive protocol-specified lumbar punctures

Exclusion criteria

• Age < 18 years
• Receipt of >=3 doses of amphotericin therapy
• Cannot or unlikely to attend regular clinic visits
• History of known liver cirrhosis
• Presence of jaundice
• Pregnancy
• Current breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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460 participants in 2 patient groups

Placebo

No Intervention group

Description:

Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day) + placebo

Sertraline 400mg

Experimental group

Description:

Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day plus adjunctive sertraline therapy at 400mg/day for 2 weeks, then 200mg for 12 weeks, and then tapered over 3 weeks.

Treatment:

Drug: Sertraline