Rebecca H McLeese, Brenda O'Neill, Daniel F McAuley, Mike Clarke, Andrew Jackson, Christina Campbell, Kathryn Ferguson, Ryan McChrystal, Anthony De Soyza, James D Chalmers, Fiona Copeland, J Stuart Elborn, Judy M Bradley, CLEAR Investigator Team
54 research coordinators (20 sites) were remotely trained/deemed competent, and 52 conducted at least one DRA. 145 patients completed DRAs: 144 were correctly classified, one was misclassified as pass (found during quality checks). 12 were classified as fail in the first DRA: seven had ≥15% FEV1 drop, two had 10%-15% FEV1 drop with symptoms, one had severe coughing (clinical team did not recruit) and the reason was not documented for two. 11 repeated the DRA; nine passed and continued in the trial, two failed and were excluded. 142/145 were classified as pass and entered the trial. Of 142 patients who continued in the trial, 46 later withdrew from HTS. 17 withdrawals were related to issues with HTS tolerance despite passing the first DRA.
INTRODUCTION: A drug response assessment (DRA) is recommended before starting patients on hypertonic saline (HTS) due to the risk of bronchoconstriction. As part of the CLEAR trial (a randomised, open-label trial of HTS and/or carbocisteine versus usual care in bronchiectasis), we performed a post hoc analysis to explore the implementation and outcomes of DRAs. We aimed to remotely train/assess research coordinators in performing DRAs and determine patient safety/tolerability with HTS.
METHODS: Research coordinators were remotely trained/deemed DRA competent. DRAs were conducted only in patients assigned HTS. Failure was classified as ≥15% forced expiratory volume in 1 s (FEV1) drop or 10%-15% drop with respiratory symptoms.
RESULTS: 54 research coordinators (20 sites) were remotely trained/deemed competent, and 52 conducted at least one DRA. 145 patients completed DRAs: 144 were correctly classified, one was misclassified as pass (found during quality checks). 12 were classified as fail in the first DRA: seven had ≥15% FEV1 drop, two had 10%-15% FEV1 drop with symptoms, one had severe coughing (clinical team did not recruit) and the reason was not documented for two. 11 repeated the DRA; nine passed and continued in the trial, two failed and were excluded. 142/145 were classified as pass and entered the trial. Of 142 patients who continued in the trial, 46 later withdrew from HTS. 17 withdrawals were related to issues with HTS tolerance despite passing the first DRA.
DISCUSSION: DRA failure rate was low and did not identify medium-term/long-term tolerance to HTS, indicating that its utility as a screening tool for tolerability in this population is limited.
TRIAL REGISTRATION NUMBER: ISRCTN89040295.