Evidence map›Paper›PMID 33527139›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2021

Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia.

Deborah P Merke, Ashwini Mallappa, Wiebke Arlt, Aude Brac de la Perriere, Angelica Lindén Hirschberg, Anders Juul, John Newell-Price, Colin G Perry, Alessandro Prete, D Aled Rees and 7 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07099456 (Channelling Fertility And Sexual Function In Congenital Adrenal Hyperplasia. CALLIOPE), which is not on this map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.8field-weighted citation impact, top 4% 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.

NCT07099456 recruitingnot on this mapstarted 2024, after this paper: background citation

Channelling Fertility And Sexual Function In Congenital Adrenal Hyperplasia. CALLIOPE: An Observational, Longitudinal Pilot Study

TypeobservationalSponsorUniversity of Roma La SapienzaRan2024 to 2030Enrolled50ConditionsCongenital Adrenal Hyperplasia (CAH)
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 81 citations in OpenAlex.

  1. Trial
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  6. 24-Hour Profiles of 11-Oxygenated CFrontiers in endocrinology · 2021
    Trial
  7. Review
  8. Review
  9. Article
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  14. Modified-release hydrocortisone (EfmodyFrontiers in endocrinology · 2026
    Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Cardiac function in children with congenital adrenal hyperplasia.Journal of pediatric endocrinology & metabolism : JPEM · 2025
    Article
  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

17 authors at 14 institutions in 7 countries.

Deborah P MerkeNational Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Ashwini MallappaNational Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Wiebke ArltInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Aude Brac de la PerriereHospices Civils de Lyon, Fédération d'Endocrinologie, Groupement hospitalier Est, Bron Cedex, France.
Angelica Lindén HirschbergDepartment of Women's and Children's Health, Karolinska Institutet and Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Anders JuulDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
John Newell-PriceUniversity of Sheffield, Sheffield, UK.
Colin G PerryQueen Elizabeth University Hospital, Glasgow, UK.
Alessandro PreteInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
D Aled ReesNeuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
Nicole ReischMedizinische Klinik IV, Klinikum der Universität München, Munich, Germany.
Nike StikkelbroeckRadboud University Medical Centre, GA Nijmegen, the Netherlands.
Philippe TouraineDepartment of Endocrinology and Reproductive Medicine, Pitie Salpêtriere Hospital, France.
Kerry MaltbyDiurnal Ltd, Cardiff, UK.
F Peter TreasurePeter Treasure Statistical Services Ltd, Kings Lynn, UK.
John PorterDiurnal Ltd, Cardiff, UK.
Richard J RossUniversity of Sheffield, Sheffield, UK.
Diurnal (United Kingdom) · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBCardiff University · GBEunice Kennedy Shriver National Institute of Child Health and Human Development · USHospices Civils de Lyon · FRKarolinska University Hospital · SELMU Klinikum · DENational Institutes of Health Clinical Center · USQueen Elizabeth University Hospital · GBRadboud University Nijmegen · NLRoyal Statistical Society · GBSorbonne Université · FRUniversity of Copenhagen · DKUniversity of Sheffield · GB

Funding

Modified-release Hydrocortisone Therapy as a Treatment for CAHZIAHD008931 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MERKE, DEBORAH · 2014 to 2021
$6k
6 · The paper itself

Abstract

contextStandard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes.

objectiveWe investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control.

methodsA 6-month, randomized, phase 3 study was conducted of MR-HC vs standard glucocorticoid, followed by a single-arm MR-HC extension study. Primary outcomes were change in 24-hour SD score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase 3, and efficacy, safety and tolerability of MR-HC for the extension study.

resultsThe phase 3 study recruited 122 adult CAH patients. Although the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P = .007) and 12 (P = .019) weeks, and between 07:00h to 15:00h (P = .044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (< 1200 ng/dL) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P = .002), and 80% for MR-HC at 18 months' extension. The median daily hydrocortisone dose was 25 mg at baseline, at 6 months 31 mg for standard therapy, and 30 mg for MR-HC, and after 18 months 20 mg MR-HC. Three adrenal crises occurred in phase 3, none on MR-HC and 4 in the extension study. MR-HC resulted in patient-reported benefit including menses restoration in 8 patients (1 on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy).

conclusionMR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.

Indexed as

Adrenal Hyperplasia, CongenitalAdultAgedAnti-Inflammatory AgentsFemaleFollow-Up StudiesHumansHydrocortisoneMaleMiddle AgedPrognosisYoung AdultAnti-Inflammatory AgentsHydrocortisone21-hydroxylase deficiencyadrenal insufficiencycongenital adrenal hyperplasiaglucocorticoidhydrocortisone

Identifiers

PMID33527139
PMCPMC8063257
OpenAlexW3127984913

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.