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Trial record 34 of 53 for:    "Cryptococcosis"

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

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ClinicalTrials.gov Identifier: NCT01802385
Recruitment Status : Completed
First Posted : March 1, 2013
Last Update Posted : February 14, 2018
Sponsor:
Collaborators:
Infectious Disease Institute, Kampala, Uganda
National Institute of Neurological Disorders and Stroke (NINDS)
Mbarara University of Science and Technology
Medical Research Council
Wellcome Trust
Makerere University
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cryptococcal Meningitis Fungal Meningitis Drug: Sertraline Phase 3

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis
Actual Study Start Date : March 9, 2015
Actual Primary Completion Date : September 2017
Actual Study Completion Date : September 27, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Meningitis
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day).
Drug: Sertraline
Sertraline 400mg/day for 2 weeks, then 200mg/day for 12 weeks, then tapered over 3 weeks.
Other Names:
  • Zoloft
  • Lustral
Experimental: Sertraline 400mg
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.
Drug: Sertraline
Sertraline 400mg/day for 2 weeks, then 200mg/day for 12 weeks, then tapered over 3 weeks.
Other Names:
  • Zoloft
  • Lustral



Primary Outcome Measures :
  1. Survival [ Time Frame: 18 weeks ]
    18-week survival. The comparison will be between sertraline 400mg group and placebo


Secondary Outcome Measures :
  1. Safety [ Time Frame: 18 weeks ]
    Safety and tolerability of adjunctive sertraline (grade 4-5) adverse reactions)

  2. Intolerance [ Time Frame: 18 weeks ]
    Time to dose-reduction for intolerance

  3. Microbiologic [ Time Frame: 14 days ]
    2 week CSF culture sterility

  4. Neurocognitive Performance [ Time Frame: 14 weeks ]
    Quantitative neurocognitive performance score (QNPZ-8) and Center for Epidemiologic Studies in Depression (CES-D) scale at 14 weeks.

  5. Early Fungicidal Activity [ Time Frame: 14 days ]
    To determine whether adjunctive sertraline will lead to a faster rate of fungal clearance from cerebrospinal fluid (CSF), as measured by early fungicidal activity (EFA) of clearance of the Cryptococcus colony forming units (cfu) per mL of CSF per day, compared to standard therapy alone.

  6. IRIS and Relapse Incidence [ Time Frame: 18 weeks ]
    Cumulative incidence of central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse

  7. Event free survival [ Time Frame: 18 weeks ]
    Event free survival of composite events of: death,central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse.


Other Outcome Measures:
  1. Cost analysis [ Time Frame: 18 weeks ]
    Cost-benefit of adjunctive sertraline therapy

  2. Switching to Open Label Sertraline [ Time Frame: 14 weeks ]
    Incidence of switching from blinded to open-labeled study drug due to severe depression occurring between 4 to 14 weeks.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01802385


Locations
Uganda
Infectious Disease Institute
Kampala, Uganda
Mbarara University of Science and Technology
Mbarara, Uganda
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Infectious Disease Institute, Kampala, Uganda
National Institute of Neurological Disorders and Stroke (NINDS)
Mbarara University of Science and Technology
Medical Research Council
Wellcome Trust
Makerere University
Investigators
Principal Investigator: David B Meya, MBCHB MMed Infectious Disease Institute
Study Director: Joshua Rhein, MD University of Minnesota - Clinical and Translational Science Institute
Study Chair: David R Boulware, MD MPH University of Minnesota - Clinical and Translational Science Institute

Additional Information:
Publications:
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01802385     History of Changes
Other Study ID Numbers: S4 0296-01
R01NS086312-01 ( U.S. NIH Grant/Contract )
First Posted: March 1, 2013    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
cryptococcal meningitis
cryptococcus
meningitis
yeast
fungus

Additional relevant MeSH terms:
Cryptococcosis
Meningitis
Meningitis, Cryptococcal
Meningitis, Fungal
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Fungal Infections
Mycoses
Central Nervous System Infections
Sertraline
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs