Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis
NCT ID: NCT01802385
Last Updated: 2020-06-09
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
460 participants
INTERVENTIONAL
2015-03-09
2017-09-27
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Placebo
Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day) + placebo
No interventions assigned to this group
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.
Sertraline
Sertraline 400mg/day for 2 weeks, then 200mg/day for 12 weeks, then tapered over 3 weeks.
Interventions
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Sertraline
Sertraline 400mg/day for 2 weeks, then 200mg/day for 12 weeks, then tapered over 3 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Infectious Disease Institute, Kampala, Uganda
OTHER
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Mbarara University of Science and Technology
OTHER
Medical Research Council
OTHER_GOV
Wellcome Trust
OTHER
Makerere University
OTHER
University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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David B Meya, MBCHB MMed
Role: PRINCIPAL_INVESTIGATOR
Infectious Disease Institute
Joshua Rhein, MD
Role: STUDY_DIRECTOR
University of Minnesota
David R Boulware, MD MPH
Role: STUDY_CHAIR
University of Minnesota
Locations
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Infectious Disease Institute
Kampala, , Uganda
Mbarara University of Science and Technology
Mbarara, , Uganda
Countries
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References
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Rhein J, Morawski BM, Hullsiek KH, Nabeta HW, Kiggundu R, Tugume L, Musubire A, Akampurira A, Smith KD, Alhadab A, Williams DA, Abassi M, Bahr NC, Velamakanni SS, Fisher J, Nielsen K, Meya DB, Boulware DR; ASTRO-CM Study Team. Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study. Lancet Infect Dis. 2016 Jul;16(7):809-818. doi: 10.1016/S1473-3099(16)00074-8. Epub 2016 Mar 10.
Zhai B, Wu C, Wang L, Sachs MS, Lin X. The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections. Antimicrob Agents Chemother. 2012 Jul;56(7):3758-66. doi: 10.1128/AAC.00212-12. Epub 2012 Apr 16.
Smith KD, Achan B, Hullsiek KH, McDonald TR, Okagaki LH, Alhadab AA, Akampurira A, Rhein JR, Meya DB, Boulware DR, Nielsen K; ASTRO-CM/COAT Team. Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda. Antimicrob Agents Chemother. 2015 Dec;59(12):7197-204. doi: 10.1128/AAC.01299-15. Epub 2015 Aug 31.
Rhein J, Huppler Hullsiek K, Tugume L, Nuwagira E, Mpoza E, Evans EE, Kiggundu R, Pastick KA, Ssebambulidde K, Akampurira A, Williams DA, Bangdiwala AS, Abassi M, Musubire AK, Nicol MR, Muzoora C, Meya DB, Boulware DR; ASTRO-CM team. Adjunctive sertraline for HIV-associated cryptococcal meningitis: a randomised, placebo-controlled, double-blind phase 3 trial. Lancet Infect Dis. 2019 Aug;19(8):843-851. doi: 10.1016/S1473-3099(19)30127-6.
Sadiq A, Kwizera R, Kiiza TK, Ayebare P, Ahimbisibwe C, Ndyetukira JF, Boulware DR, Meya DB. Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda. AIDS Res Ther. 2025 Feb 19;22(1):21. doi: 10.1186/s12981-025-00705-z.
Okurut S, Boulware DR, Okafor E, Rhein J, Kajumbula H, Bagaya BS, Bwanga F, Olobo JO, Manabe YC, Meya DB, Janoff EN. Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis. Front Immunol. 2023 Dec 13;14:1275443. doi: 10.3389/fimmu.2023.1275443. eCollection 2023.
Bahr NC, Skipper CP, Huppler-Hullsiek K, Ssebambulidde K, Morawski BM, Engen NW, Nuwagira E, Quinn CM, Ramachandran PS, Evans EE, Lofgren SM, Abassi M, Muzoora C, Wilson MR, Meya DB, Rhein J, Boulware DR. Recurrence of Symptoms Following Cryptococcal Meningitis: Characterizing a Diagnostic Conundrum With Multiple Etiologies. Clin Infect Dis. 2023 Mar 21;76(6):1080-1087. doi: 10.1093/cid/ciac853.
Lofgren SM, Nicol MR, Kandole TK, Castillo-Mancilla J, Anderson PL, Mpoza E, Tugume L, Bangdiwala AS, Ssebambulidde K, Hullsiek KH, Rhein J, Meya DB, Boulware DR. Short Communication: A Descriptive Analysis of Dried Blood Spot Adherence Testing Among Ugandans with HIV Presenting with Cryptococcal Meningitis. AIDS Res Hum Retroviruses. 2021 Jul;37(7):529-533. doi: 10.1089/AID.2020.0202. Epub 2021 Apr 12.
Kwizera R, Sadiq A, Ndyetukira JF, Nalintya E, Williams D, Rhein J, Boulware DR, Meya DB; COAT and ASTRO trial teams. Impact of community engagement and social support on the outcomes of HIV-related meningitis clinical trials in a resource-limited setting. Res Involv Engagem. 2020 Aug 20;6:49. doi: 10.1186/s40900-020-00228-z. eCollection 2020.
Ahimbisibwe C, Kwizera R, Ndyetukira JF, Kugonza F, Sadiq A, Hullsiek KH, Williams DA, Rhein J, Boulware DR, Meya DB. Management of amphotericin-induced phlebitis among HIV patients with cryptococcal meningitis in a resource-limited setting: a prospective cohort study. BMC Infect Dis. 2019 Jun 26;19(1):558. doi: 10.1186/s12879-019-4209-7.
Atherton RR, Ellis J, Cresswell FV, Rhein J, Boulware DR. Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort. Wellcome Open Res. 2018 Oct 12;3:80. doi: 10.12688/wellcomeopenres.14666.2. eCollection 2018.
Tugume L, Rhein J, Hullsiek KH, Mpoza E, Kiggundu R, Ssebambulidde K, Schutz C, Taseera K, Williams DA, Abassi M, Muzoora C, Musubire AK, Meintjes G, Meya DB, Boulware DR; COAT and ASTRO-CM teams. HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts. J Infect Dis. 2019 Feb 23;219(6):877-883. doi: 10.1093/infdis/jiy602.
Ssebambulidde K, Bangdiwala AS, Kwizera R, Kandole TK, Tugume L, Kiggundu R, Mpoza E, Nuwagira E, Williams DA, Lofgren SM, Abassi M, Musubire AK, Cresswell FV, Rhein J, Muzoora C, Hullsiek KH, Boulware DR, Meya DB; Adjunctive Sertraline for Treatment of HIV-associated Cryptococcal Meningitis Team. Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis. Clin Infect Dis. 2019 May 30;68(12):2094-2098. doi: 10.1093/cid/ciy817.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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Infectious Disease Institute
Accordia Global Health Foundation
Other Identifiers
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S4 0296-01
Identifier Type: -
Identifier Source: org_study_id
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