Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials.

ABSTRACT:

Background

In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks.

Methods

We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per m

SUBMITTER: Pullen MF 

PROVIDER: S-EPMC7755087 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature