Trial reportThe Journal of clinical endocrinology and metabolism2022
Randomized Trial of Osilodrostat for the Treatment of Cushing Disease.
Trial report in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase III, Multi-center, Randomized, Double-blind, 48 Week Study With an Initial 12 Week Placebo-controlled Period to Evaluate the Safety and Efficacy of Osilodrostat in Patients With Cushing's Disease
Osilodrostat Therapy and 11C-methionine PET to IMprove Corticotroph Pituitary Adenoma Detection and Localisation in Patients With Cushing's Disease
Combination Osilodrostat and Cabergoline Versus Osilodrostat Alone in Cushing's Disease in Iraq: Assessment of Efficacy and Safety
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The effect of hypercortisolism treatment on dyslipidemia in Cushing syndrome: systematic review and meta-analysis.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Impact of Osilodrostat on Health-Related Quality of Life in Cushing's Disease: Analysis of Patient-Reported Outcomes From the Phase III LINC 3 and LINC 4 Clinical Trials.Clinical endocrinology · 2026Trial
- Osilodrostat treatment in patients with Cushing's disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4).Endocrine journal · 2024Trial
- Trial
- Ectopic ACTH-dependent Cushing syndrome in 3 hospitalized patients: lessons learned from management with osilodrostat.JCEM case reports · 2026Article
- Is Hypercortisolism Treatable? Which Patients Should Be Treated and How-A Practical Guide for Clinicians.Diabetes, obesity & metabolism · 2026Review
- Efficacy and safety of osilodrostat in patients with ectopic Cushing's syndrome.Hormones (Athens, Greece) · 2026Review
- International real-world study on osilodrostat efficacy and safety in adrenal Cushing syndrome.The Journal of clinical endocrinology and metabolism · 2026Article
- Etomidate in severe hypercortisolism: early cortisol kinetics and clinical outcomes in a real-world cohort.Pituitary · 2026Article
- Histopathological evidence of osilodrostat-induced regression of a cortisol-producing adrenocortical adenoma.JCEM case reports · 2026Article
- Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement.The Journal of clinical endocrinology and metabolism · 2026Review
- Update and Practical Recommendations for the Use of Medical Treatment of Cushing Syndrome.Endocrine reviews · 2026Review
- Real-World Osilodrostat Effectiveness and Safety in Nonpituitary Cushing Syndrome.The Journal of clinical endocrinology and metabolism · 2026Observational
- Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. a real-world study in Spain.Journal of endocrinological investigation · 2026Article
- Use of osilodrostat in a block-and-replace and titration strategy for cushing's syndrome: a position paper by French experts.Reviews in endocrine & metabolic disorders · 2026Article
- Early hypocortisolism with persistent remission following osilodrostat in a patient with long-standing Cushing disease.JCEM case reports · 2026Article
- A case of prolonged adrenal insufficiency following osilodrostat discontinuation with a review of the literature.Endocrine journal · 2026Review
- Individualized osilodrostat treatment for patients with ACTH-dependent Cushing's syndrome: real-world evidence.Frontiers in endocrinology · 2026Article
- Beyond the MRI-positive/MRI-negative dichotomy: A stepwise surgical strategy for Cushing's disease.Brain & spine · 2026Article
- Controlling cortisol excess and comorbidities in Cushing's syndrome with osilodrostat.Pituitary · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 13 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextCushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal.
objectiveWe aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease.
methodsLINC 4 was a phase III, multicenter trial comprising an initial 12-week, randomized, double-blind, placebo-controlled (osilodrostat:placebo, 2:1) period followed by a 36-week, open-label treatment period (NCT02697734). Adult patients (aged 18-75 years) with confirmed Cushing disease and mean urinary free cortisol (mUFC) excretion ≥ 1.3 times the upper limit of normal (ULN) were eligible. The primary endpoint was the proportion of randomized patients with mUFC ≤ ULN at week 12. The key secondary endpoint was the proportion achieving mUFC ≤ ULN at week 36 (after 24 weeks' open-label osilodrostat).
resultsSeventy-three patients (median age, 39 years [range, 19-67]; mean/median mUFC, 3.1 × ULN/2.5 × ULN) received randomized treatment with osilodrostat (n = 48) or placebo (n = 25). At week 12, significantly more osilodrostat (77%) than placebo (8%) patients achieved mUFC ≤ ULN (odds ratio 43.4; 95% CI 7.1, 343.2; P < 0.0001). Response was maintained at week 36, when 81% (95% CI 69.9, 89.1) of all patients achieved mUFC ≤ ULN. The most common adverse events during the placebo-controlled period (osilodrostat vs placebo) were decreased appetite (37.5% vs 16.0%), arthralgia (35.4% vs 8.0%), and nausea (31.3% vs 12.0%).
conclusionOsilodrostat rapidly normalized mUFC excretion in most patients with Cushing disease and maintained this effect throughout the study. The safety profile was favorable.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.