Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies

Leuk Lymphoma. 2011 Feb;52(2):179-93. doi: 10.3109/10428194.2010.542600.

Abstract

Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests (ClinicalTrials.gov number, NCT00163722).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Aspergillosis / diagnosis*
  • Aspergillosis / drug therapy
  • Aspergillosis / microbiology
  • Enzyme-Linked Immunosorbent Assay
  • Galactose / analogs & derivatives
  • Hematologic Neoplasms / diagnosis*
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / microbiology
  • Humans
  • Mannans / blood
  • Polymerase Chain Reaction
  • Randomized Controlled Trials as Topic
  • Research Design
  • Risk Factors

Substances

  • Antifungal Agents
  • Mannans
  • galactomannan
  • Galactose

Associated data

  • ClinicalTrials.gov/NCT00163722