A 2x2 factorial, randomised, open-label trial to determine the clinical and cost- effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: A protocol for the CLEAR clinical trial
Bibliographic record
Abstract
Abstract Background Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum-removal as part of standard care. We hypothesise that mucoactive agents (HTS or cabocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. Methods A 52-week, 2x2 factorial randomised open label trial to determine the clinical and cost-effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care: CLEAR (clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care). Patients will be randomised to either (i) Standard care and twice daily nebulised HTS (6%), (ii) Standard care and carbocisteine (750mg three times per day until visit 3 reducing to 750mg twice per day), (iii) Standard care and combination of twice-daily nebulised HTS and carbocisteine, or (iv) Standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria: adults with a diagnosis of BE on computed tomography scans, BE as the primary respiratory diagnosis, two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. Discussion This trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigor in other areas of trial-delivery. CLEAR will provide evidence as to whether HTS, carbocisteine or both are effective and cost-effective for BE patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.015 |
| Meta-epidemiology (narrow) | 0.006 | 0.002 |
| Meta-epidemiology (broad) | 0.008 | 0.006 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.004 |
| Scholarly communication | 0.003 | 0.004 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.008 | 0.005 |
| Insufficient payload (model declined to judge) | 0.027 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".