Effect of Calcium Channel Blockers on Lung Function in Placebo-treated Patients in Idiopathic Pulmonary Fibrosis Trials
Bibliographic record
Abstract
Abstract Rationale: Currently, only two approved medications have been demonstrated to slow the progression of idiopathic pulmonary fibrosis (IPF). There remains an unmet need for more effective IPF therapies. Several preclinical studies have suggested that calcium channel blockers (CCBs) have potential antifibrotic effects. This study aims to evaluate the effect of CCBs on IPF progression. Methods: A post-hoc pooled analysis of data from placebo-treated participants in five IPF randomized clinical trials (RCTs) (CAPACITY-004, CAPACITY-006, ASCEND, INPULSIS-1, and INPULSIS-2) was conducted. Raw data from the Vivli platform were used following approval from the trial sponsors for secondary data analysis. The primary outcome was the change in percent (%) predicted forced vital capacity (FVC) from baseline to one year in patients on CCB at baseline compared to those not on CCB. The change was assessed using a three-level multilevel mixed-effects model, which accounts for the hierarchical structure of the data, with repeated measures (level 1) nested within individuals (level 2) nested within trials (level 3). Covariates included time (days since baseline), baseline CCB, trial- and participant-level baseline % predicted FVC, hypertension, and interactions with time. The secondary outcomes included the change in % predicted hemoglobin-corrected DLCO (DLCOcHb) and one-year survival, which was analyzed via Kaplan-Meier curves. Results: Among the placebo-treated patients, 13.2% (134/1013) were taking CCBs at baseline. There was evidence of a significant interaction effect between CCB use and time (p=0.037), suggesting that CCBs may slightly worsen the % predicted FVC over time. Overall, the % predicted FVC declined in absolute units by an average 6.77% per year for those not on CCBs. For the CCB group, there was an estimated additional 1.74% (95% CI: 0.1% to 3.51%) steeper average yearly decline, independent of hypertension (Figure). There was no significant differential effect of CCB use on changes in % predicted DLCOcHb. Additionally, there was no significant difference in the Kaplan-Meier estimated one-year survival between the groups (log-rank p=0.17). Conclusion: Post-hoc analysis of five previously conducted RCTs involving IPF patients revealed that CCBs were associated with a slightly steeper yearly decline in lung function. These data question the clinical relevance of the preclinical models suggesting benefits of CCBs.
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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 | 0.024 | 0.029 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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".