MétaCan
Menu
Back to cohort
Record W4366332482 · doi:10.1007/s41030-023-00222-2

Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis

2023· article· en· W4366332482 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenuePulmonary Therapy · 2023
Typearticle
Languageen
FieldMedicine
TopicSarcoidosis and Beryllium Toxicity Research
Canadian institutionsnot available
FundersMallinckrodt Pharmaceuticals
KeywordsPlaceboMedicineAdverse effectDiscontinuationSarcoidosisInternal medicineClinical trialPulmonary function testingRandomized controlled trialGlucocorticoidSurgeryPathology

Abstract

fetched live from OpenAlex

Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. ClinicalTrials.gov identifier: NCT03320070. Pulmonary sarcoidosis is a disease characterized by inflammation of the lungs. Standard treatments include glucocorticoids, which may have harmful side effects. This clinical trial investigated whether repository corticotropin injection (RCI, Acthar® Gel) was safe and effective in patients who were already taking glucocorticoids to treat pulmonary sarcoidosis. Patients were randomly assigned to be in one of two treatment groups: RCI or placebo. In the first 24 weeks of the study, 27 patients were injected with RCI twice weekly, while 28 patients were injected with an inactive substance (placebo). Forty-seven patients continued into an optional phase of the study for an additional 24 weeks in which all patients received RCI twice weekly. A sarcoidosis treatment score and assessments of lung health, general health, and fatigue were used to determine whether RCI was effective. These assessments showed greater improvements with RCI compared to placebo. Patients who switched from placebo to RCI showed similar improvements to those who remained on RCI throughout the entire study. Patients receiving RCI were able to discontinue their use of glucocorticoids more quickly than those taking placebo, thus helping them to avoid the harmful side effects of the glucocorticoids. Side effects for RCI were mostly mild or moderate, and no new or unexpected safety concerns for RCI were seen throughout the study.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.065
Threshold uncertainty score0.777

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.081
GPT teacher head0.371
Teacher spread0.289 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it