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Riociguat for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH): Final data from a phase II long-term extension (LTE) study

2015· article· en· W2463534771 on OpenAlexaff
Marius M. Hoeper, Michael Halank, F. Joachim Meyer, G. Stähler, Jürgen Behr, Ralf Ewert, Monique Fletcher, Pablo Colorado, Sylvia Nikkho, Janethe de Oliveira Pena, Friedrich Grimminger

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicPulmonary Hypertension Research and Treatments
Canadian institutionsUniversity Hospital
Fundersnot available
KeywordsMedicineRiociguatTolerabilityChronic thromboembolic pulmonary hypertensionInternal medicineAdverse effectPopulationPeripheral edemaPulmonary hypertensionGastroenterology

Abstract

fetched live from OpenAlex

Background: Riociguat was well tolerated and significantly improved 6MWD and WHO FC in a Phase II study of pts with PAH or CTEPH. We present final safety and efficacy data from the LTE phase of this study. Methods: Pts with PAH or CTEPH completing the initial 12-wk trial were eligible to enter the LTE. All pts received riociguat individually adjusted to a maximum dose of 2.5 mg three-times daily (tid). The primary outcome was safety and tolerability; secondary outcomes included change from baseline in 6MWD and WHO FC. Results: Of 72 pts in the initial study, 68 (94%) entered the LTE. At study completion, median treatment duration was 77 months (range 3–87 months). Thirty-six (53%) pts remained in the LTE until completion and 32 (47%) discontinued treatment; 11 (16%) due to death (all judged unrelated to study drug) and 6 (9%) due to adverse events (AEs). AEs and serious AEs were reported by 63 (93%) and 52 (76%) pts, respectively. Nasopharyngitis (57%) and peripheral edema (37%; 3% drug-related) were the most common AEs. Mean±SD 6MWD increased from baseline by 58±104 m (n=36) in the overall population at Month 72, and by 87±121 m (n=13) and 41±91 m (n=23) in pts with PAH and CTEPH, respectively. At Month 72, WHO FC had improved/stabilized/worsened vs baseline in 51/43/5% of the overall population (n=37), 62/38/0% of PAH pts (n=13), and 46/46/8% of CTEPH pts (n=24). Survival in the overall population at approximately 9, 36, and 72 months was 97, 91, and 81%, respectively. Conclusions: Riociguat is generally well tolerated in pts with PAH and CTEPH, and led to sustained improvements in 6MWD and WHO FC for up to 6 years.

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.

How this classification was reachedexpand

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmano category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Observationallow
gptno category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Non-randomized trialhigh
models splitAgreement compares identical category sets and study designs across arms.

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.186
GPT teacher head0.376
Teacher spread0.190 · 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

Classification

machine, unvalidated

Labeled directly by 2 models reading the full record.

The models applied no category: nothing in the taxonomy fit this work.

The models disagree on parts of this classification; every voice is preserved in the section at the end of the page.

Study designObservational · Non-randomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2015
Admission routes1
Has abstractyes

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