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Record W4306757577 · doi:10.1016/j.kint.2022.09.017

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

2022· article· en· W4306757577 on OpenAlexaff
Jonathan Barratt, Richard Lafayette, Jens Kristensen, Andrew Stone, Daniel Cattran, Jürgen Floege, Vladimı́r Tesař, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Brad H. Rovin, Guillermo Fragale, Alejandra Karl, Patricia Losisolo, Ivan Gonzalez Hoyos, Mauro Lampo, Matías Monkowski, Jorge de la Fuente, Magdalena Alvarez, Daniela Stoppa, Carlos Chiurchiu, P. Novoa, Marcelo Orías, Maria Belen Barron, Ana Paula Giotto, M. Arriola, Evelin Cassini, Rafaël Maldonado, Maria Paula Dionisi, Jessica Ryan, Nigel D. Toussaint, Grant Luxton, Chen Au Peh, Vicki Levidiotis, Ross S. Francis, Richard Phoon, Elena Fedosiuk, D.M. Toropilov Toropilov, R. E. Yakubtsevich, Elena Mikhailova, Christophe Bovy, Nathalie Demoulin, Jean‐Michel Hougardy, Bart Maes, Marijn M. Speeckaert, Louis‐Philippe Laurin, Sean Barbour, Mélanie Masse, Michelle Hladunewich, Heather N. Reich, Serge Cournoyer, Karthik Tennankore, Jicheng Lv, Zhangsuo Liu, Caili Wang, Shaomei Li, Qun Luo, Zhaohui Ni, Tiekun Yan, Ping Fu, Hong Cheng, Bi‐Cheng Liu, Wanhong Lu, Jianqin Wang, Qinkai Chen, D. Wang, Zuying Xiong, Menghua Chen, Yan Xu, Jiali Wei, Pearl Pai, Lianhua Chen, Jitka Řehořová, Dita Maixnerová, Roman Šafránek, Ivan Rychlík, M Hrubý, Satu Mäkelä, Kati Vääräniemi, Fernanda Ortiz, É. Alamartine, Maïté Daroux, C. Cartery, François Vrtovsnik, Jean‐Emmanuel Serre, Eleni Stamellou, Volker Vielhauer, Christian Hugo, Klemens Budde, Britta Otte, Martin Nitschke, Evangelia Ntounousi, Ioannis Boletis, Αikaterini Papagianni, Dimitrios Goumenos, Kostas Stylianou, Synodi Zermpala, Ciro Esposito, Mario Cozzolino, Sara Viganò, Loreto Gesualdo, Michał Nowicki, Tomasz Stompór, Ilona Kurnatowska, Sung Gyun Kim, Yong-Lim Kim, Ki Ryang Na, Dong Ki Kim, Su‐Hyun Kim, Luis Quintana Porras, Eva Rodriguez Garcia, Irene Agraz Pamplona, Alfons Segarra, Marián Goicoechea, Bengt Fellström, Sigrid Lundberg, Peter Hemmingsson, Gregor Guron, Anna Sandell, Cheng‐Hsu Chen, Bülent Tokgöz, Soner Duman, Mehmet Rıza Altıparmak, Metin Ergül, Patrick B. Mark, Kieran McCafferty, Arif Khwaja, Chee Kay Cheung, Matt Hall, Albert Power, Durga Kanigicherla, Richard J. Baker, Jim Moriarty, Amr Mohamed, Joseph Aiello, Pietro A. Canetta, Isabelle Ayoub, Derrick Robinson, Surabhi Thakar, Amy K. Mottl, Isaac Sachmechi, Bernard Fischbach, Harmeet Singh, Jeffrey Mulhern, Fahmeedah Kamal, Douglas Linfert, Dana V. Rizk, Shikha Wadhwani, Menaka Sarav, Kirk N. Campbell, Gaia Coppock, Randy L. Luciano, John R. Sedor, Rupali S. Avasare, Wai Lang Lau

Bibliographic record

VenueKidney International · 2022
Typearticle
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsToronto General HospitalUniversity of Toronto
Fundersnot available
KeywordsPlaceboMedicineRenal functionClinical endpointUrologyBudesonideAdverse effectInternal medicineRandomized controlled trialClinical trialNephropathyKidney diseaseGastroenterologyCorticosteroidPathologyEndocrinologyDiabetes mellitus

Abstract

fetched live from OpenAlex

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m 2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN 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.

How this classification was reachedexpand

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)0.005
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.010
Threshold uncertainty score0.033

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.003
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0100.001

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 head0.039
GPT teacher head0.306
Teacher spread0.267 · 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

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

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

Citations215
Published2022
Admission routes1
Has abstractyes

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