Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Abstract

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.

Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.

Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to -11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was -26 [-29, -23]. Odds of -26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).

Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.

Keywords: Clinical trials; Cystic fibrosis; Exacerbations; Symptoms.

Conflict of interest statement

Declaration of Competing Interest None

Copyright © 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1.. Notch-and-whisker plot of CRISS measure distributions by study day.

Horizontal lines within boxes are median values, boxes identify interquartile ranges, notches display median confidence intervals, and whiskers display ranges. Means are shown as solid circles and outliers as open circles.

Figure 2.. Kaplan Meier curves of time to achieving 11-point and 26-point CRISS reductions from baseline.

Time to an 11-point CRISS reduction from baseline is shown as a solid line; time to a 26-point reduction is shown as a hashed line.

Figure 3.. CRISS values at baseline, Day 14, and Day 28 stratified by age and lung function.

Panel A, box-and-whisker CRISS plots stratified by age group. Panel B, plots stratified by ppFEV1 quartiles. Boxes display medians and interquartile ranges, whiskers display ranges, solid circles display means, and open circles display outliers. White bars represent baseline values; light and dark gray boxes represent Day 14 and Day 28 values, respectively.