A Phase 3 interventional study of Sertraline in Cryptococcal Meningitis and Fungal Meningitis, sponsored by University of Minnesota. Completed at 2 sites in Uganda. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-06-09.
Sponsored by University of Minnesota · Phase 3, Interventional, and Treatment
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.
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.
54 studies on the registry are indexed under Meningitis, Cryptococcal; 6 are open to participants now.
This study's enrollment of 460 is above the median of 143 across 35 interventional studies indexed under Meningitis, Cryptococcal.
Browse Meningitis, Cryptococcal studies →University of Minnesota is the lead sponsor of 1,216 studies on the registry; 197 are open to participants now.
Of its 136 completed or terminated interventional studies of FDA-regulated products, 95 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day) + placebo
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.
Also known as: Zoloft, Lustral
Survival
18-week survival. The comparison will be between sertraline 400mg group and placebo
Time frame: 18 weeks
Safety (Occurence of Adverse Events)
Safety and tolerability of adjunctive sertraline (grade 4-5) adverse reactions
Time frame: 18 weeks
Count of Participants With Cerebrospinal Fluid Sterility
Number of participants with sterile cerebrospinal fluid at 2 weeks
Time frame: 14 days
Center for Epidemiologic Studies in Depression (CES-D) Scale
Center for Epidemiologic Studies in Depression (CES-D) scale at 14 weeks. CES-D scores are based on a 20 item survey with total scores ranging from 0 to 60. Higher scores suggest a greater presence of depressive symptoms. A CES-D score of 16 or higher is interpreted to indicate a risk for depression.
Time frame: 14 weeks
Quantitative Neurocognitive Performance Score (QNPZ-8)
Quantitative neurocognitive performance Z-score (QNPZ-8) at 14 weeks. The QNPZ-8 is a mean score of testing of 8 neurocognitive domains. Eqach domain is scaled based on a Z-score where the mean = 0 for the HIV-negative Ugandan population, accounting for age and educational status. Each +1 unit is one standard deviation better than the population norm. Each -1 unit is one standard deviation worse than the population norm.
Time frame: 14 weeks
Fungal Clearance as Determined by Early Fungicidal Activity of CDF
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.
Time frame: 14 days
Number of Participants Experiencing IRIS OR Relapse
Cumulative incidence of central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse
Time frame: 18 weeks
Event Free Survival
Event free survival of composite events of: death,central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse.
Time frame: 18 weeks
| Milestone | Placebo | Sertraline 400mg |
|---|---|---|
| Started | 231 | 229 |
| Completed | 125 | 109 |
| Not completed | 106 | 120 |
| Withdrew: Death | 106 | 120 |
18-week survival. The comparison will be between sertraline 400mg group and placebo
| Participants | Placebo | Sertraline 400mg |
|---|---|---|
| Survival | 125 | 109 |
Safety and tolerability of adjunctive sertraline (grade 4-5) adverse reactions
| events | Placebo | Sertraline 400mg |
|---|---|---|
| Safety (Occurence of Adverse Events) | 121 | 141 |
Number of participants with sterile cerebrospinal fluid at 2 weeks
| Participants | Placebo | Sertraline 400mg |
|---|---|---|
| Count of Participants With Cerebrospinal Fluid Sterility | 90 | 101 |
Center for Epidemiologic Studies in Depression (CES-D) scale at 14 weeks. CES-D scores are based on a 20 item survey with total scores ranging from 0 to 60. Higher scores suggest a greater presence of depressive symptoms. A CES-D score of 16 or higher is interpreted to indicate a risk for depression.
| score on a scale | Placebo | Sertraline 400mg |
|---|---|---|
| Center for Epidemiologic Studies in Depression (CES-D) Scale | 16.6 (14.3 to 18.8) | 13.2 (11.0 to 15.5) |
Quantitative neurocognitive performance Z-score (QNPZ-8) at 14 weeks. The QNPZ-8 is a mean score of testing of 8 neurocognitive domains. Eqach domain is scaled based on a Z-score where the mean = 0 for the HIV-negative Ugandan population, accounting for age and educational status. Each +1 unit is one standard deviation better than the population norm. Each -1 unit is one standard deviation worse than the population norm.
| score | Placebo | Sertraline 400mg |
|---|---|---|
| Quantitative Neurocognitive Performance Score (QNPZ-8) | -1.4 (-1.5 to -1.2) | -1.3 (-1.4 to 1.1) |
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.
| -log10 CFU/ml/day | Placebo | Sertraline 400mg |
|---|---|---|
| General Linear Regression | 0.47 (0.4 to 0.54) | .43 (.37 to .50) |
| Mixed-Effects Regression | 0.33 (.3 to .35) | .33 (.3 to .36) |
Cumulative incidence of central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse
| Participants | Placebo | Sertraline 400mg |
|---|---|---|
| Number of Participants Experiencing IRIS OR Relapse | 9 | 5 |
Event free survival of composite events of: death,central nervous system (CNS) cryptococcal-related paradoxical immune reconstitution inflammatory syndrome (IRIS) or culture-positive relapse.
| Participants | Placebo | Sertraline 400mg |
|---|---|---|
| Event Free Survival | 116 | 103 |
Collected over 18 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 106/231 (45.9%) | 121/231 (52.4%) | 65/231 (28.1%) |
| Sertraline 400mg | 120/229 (52.4%) | 141/229 (61.6%) | 66/229 (28.8%) |
| Event | Placebo | Sertraline 400mg |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 49/231 | 54/229 |
| HyponatremiaBlood and lymphatic system disorders | 13/231 | 16/229 |
| Elevated CreatinineBlood and lymphatic system disorders | 9/231 | 13/229 |
| HypokalemiaBlood and lymphatic system disorders | 4/231 | 13/229 |
| LymphopeniaBlood and lymphatic system disorders | 9/231 | 10/229 |
| Elevated BilirubinBlood and lymphatic system disorders | 10/231 | 9/229 |
| Respiratory DistressRespiratory, thoracic and mediastinal disorders | 3/231 | 4/229 |
| NeutropeniaBlood and lymphatic system disorders | 0/231 | 4/229 |
| FeverGeneral disorders | 4/231 | 1/229 |
| Altered Mental StatusPsychiatric disorders | 1/231 | 3/229 |
| Event | Placebo | Sertraline 400mg |
|---|---|---|
| Non-serious Adverse EventsGeneral disorders | 65/231 | 66/229 |
| Age, Categorical(Participants) | Placebo | Sertraline 400mg | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 231 | 229 | 460 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Placebo | Sertraline 400mg | Total |
|---|---|---|---|
| Median | 35 (30 to 41) | 35 (29 to 40) | 35 (30 to 40) |
| Sex: Female, Male(Participants) | Placebo | Sertraline 400mg | Total |
|---|---|---|---|
| Female | 87 | 97 | 184 |
| Male | 144 | 132 | 276 |
| Race (NIH/OMB)(Participants) | Placebo | Sertraline 400mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 231 | 229 | 460 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Placebo | Sertraline 400mg | Total |
|---|---|---|---|
| Uganda | 231 | 229 | 460 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Open
Access criteria: Contact of the Principal Investigator
This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Sertraline