Sertraline in Addition to Standard of Care Treatment for Coccidioidomycosis

In this study patients will be randomized 1:2 to receive either standard of care treatment or standard of care + Sertraline 200mg/day for 2 weeks, then 400 mg/day for 50 weeks for treatment of disseminated and meningeal coccidioidomycosis.

Study Overview

• Status: Withdrawn
• Conditions: Coccidioidomycosis
• Intervention / Treatment: Drug: Sertraline

Detailed Description

Sertraline has been demonstrated to have in-vitro activity against coccidioides, and in-vivo activity against cryptococcal meningitis in clinical trials. Disseminated and meningeal coccidiodes infections require lifelong treatment, have poor outcomes, and new treatment options are needed. In this study the investigators will determine safety and tolerability of adjunctive sertraline (grade 4-5 adverse reactions) compared to standard coccidioidomycosis therapy alone.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe coccidioidomycosis infection, manifest as by one of:

  • Coccidioidal meningitis;
  • Severe pulmonary infection requiring intensive care unit level of care;
  • Disseminated infection (in clinical opinion of the investigator); or
  • Clinical progression after >2 months of high dose fluconazole.
• Laboratory confirmation of Coccidioides infection by culture, histopathology, coccidioides polymerase chain reaction, positive complement fixation titer, or Coccidioides antigen

Exclusion Criteria:

• Age < 18 years
• Cannot or unlikely to attend regular clinic visits
• Presence of jaundice or known liver cirrhosis

• Pregnancy

  • If there is a concern of pregnancy, a negative urine (or serum) pregnancy test before study entry is required.
  • Women of childbearing potential will have pregnancy test at enrollment and will be recommended to use contraception and referred to family planning services as necessary. (Refer to informed consent document.)
• Currently breastfeeding
• Active drug use (amphetamine or cocaine) or requirement for concomitant medications that raise the risk of serotonin syndrome
• Prolonged corrected QT interval or Left Bundle Branch Block on baseline electrocardiogram

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard of Care; standard of care treatment for disseminated or meningeal coccidioidomycosis
EXPERIMENTAL: Standard of Care + Sertraline; Standard of care treatment with the addition of sertraline for the treatment of disseminated or meningeal coccidioidomycosis	Drug: Sertraline; 400 mg/day sertraline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Reactions	grade 4-5 adverse reactions	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mycoses Study Group Score	scoring of clinical outcomes	2 years
Depression Screening	Patient Health Questionnaire 9	2 years
Functional Assessment	Karnofsky	2 years

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Simon Paul, MD, UCSF - Fresno

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (ACTUAL): January 22, 2019
• Study Completion (ACTUAL): January 22, 2019

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (ESTIMATE): September 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Parasitic Diseases; Protozoan Infections; Mycoses; Coccidioidomycosis; Coccidiosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: UCSF-Fresno-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO