Evidence map›Paper›PMID 36085339›Full record

Trial reportPituitary2022

Levoketoconazole in the treatment of patients with endogenous Cushing's syndrome: a double-blind, placebo-controlled, randomized withdrawal study (LOGICS).

Rosario Pivonello, Sabina Zacharieva, Atanaska Elenkova, Miklós Tóth, Ilan Shimon, Antonio Stigliano, Corin Badiu, Thierry Brue, Carmen Emanuela Georgescu, Stylianos Tsagarakis and 2 more

Open access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Pituitary, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
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  5. Trial
  6. Article
  7. Review
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  11. Article
  12. Review
  13. Medical Treatment of Cushing's Syndrome.Endocrinology and metabolism (Seoul, Korea) · 2025
    Review
  14. Article
  15. Clinical efficacy and safety of fluconazole treatment in patients with Cushing's syndrome.Therapeutic advances in endocrinology and metabolism · 2025
    Article
  16. Article
  17. New Trends in Treating Cushing's Disease.TouchREVIEWS in endocrinology · 2024
    Article
  18. Review
  19. Iatrogenic adrenal insufficiency in adults.Nature reviews. Endocrinology · 2024
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 11 institutions in 8 countries.

Rosario Pivonello *Università Federico II Di Napoli, Naples, Italy. rosario.pivonello@unina.it.
Sabina Zacharieva *Medical University Sofia, Sofia, Bulgaria.
Atanaska ElenkovaMedical University Sofia, Sofia, Bulgaria.
Miklós TóthSemmelweis University, Budapest, Hungary.
Ilan ShimonRabin Medical Center and Tel Aviv University, Tel Aviv, Israel.
Antonio StiglianoSant'Andrea Hospital, University of Rome "Sapienza", Rome, Italy.
Corin BadiuNational Institute of Endocrinology CI Parhon and "C. Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Thierry BrueAix-Marseille Université and Assistance Publique - Hôpitaux de Marseille, Hôpital de la Conception, Marseille, France.
Carmen Emanuela GeorgescuIuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Stylianos TsagarakisEvangelismos Hospital, Athens, Greece.
Fredric CohenXeris Biopharma, Chicago, IL, USA.
Maria FleseriuOregon Health and Science University, Portland, OR, USA.
Medical University of Sofia · BGAix-Marseille Université · FRAzienda Ospedaliera Sant'Andrea · ITEvangelismos Hospital · GRInstitutul Național de Endocrinologie C.I. Parhon · ROIuliu Hațieganu University of Medicine and Pharmacy · ROOregon Health & Science University · USRabin Medical Center · ILSemmelweis University · HUUniversity of Naples Federico II · ITXeris Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe efficacy of levoketoconazole for endogenous Cushing's syndrome was demonstrated in a phase 3, open-label study (SONICS). This study (LOGICS) evaluated drug-specificity of cortisol normalization.

methodsLOGICS was a phase 3, placebo-controlled, randomized-withdrawal study with open-label titration-maintenance (14-19 weeks) followed by double-blind, randomized-withdrawal (~ 8 weeks), and restoration (~ 8 weeks) phases.

results79 patients received levoketoconazole during titration-maintenance; 39 patients on a stable dose (~ 4 weeks or more) proceeded to randomization. These and 5 SONICS completers who did not require dose titration were randomized to levoketoconazole (n = 22) or placebo (n = 22). All patients with loss of response (the primary endpoint) met the prespecified criterion of mean urinary free cortisol (mUFC) > 1.5 × upper limit of normal. During randomized-withdrawal, 21 patients withdrawn to placebo (95.5%) lost mUFC response compared with 9 patients continuing levoketoconazole (40.9%); treatment difference: - 54.5% (95% CI - 75.7, - 27.4; P = 0.0002). At the end of randomized-withdrawal, mUFC normalization was observed among 11 (50.0%) patients receiving levoketoconazole and 1 (4.5%) receiving placebo; treatment difference: 45.5% (95% CI 19.2, 67.9; P = 0.0015). Restoration of levoketoconazole reversed loss of cortisol control in most patients who had received placebo. Adverse events were reported in 89% of patients during treatment with levoketoconazole (dose-titration, randomized-withdrawal, and restoration phases combined), most commonly nausea (29%) and hypokalemia (26%). Prespecified adverse events of special interest with levoketoconazole were liver-related (10.7%), QT interval prolongation (10.7%), and adrenal insufficiency (9.5%).

conclusionsLevoketoconazole reversibly normalized urinary cortisol in patients with Cushing's syndrome. No new risks of levoketoconazole treatment were identified.

Indexed as

Adrenal InsufficiencyCushing SyndromeHumansHydrocortisoneLogicTreatment OutcomeHydrocortisoneCushing’s diseaseCushing’s syndromeHypercortisolismLevoketoconazolePlaceboSteroidogenesis inhibitor

Identifiers

PMID36085339
PMCPMC9675660
OpenAlexW4295027287

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.