Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active- controlled clinical trial

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorHEERSPINK, Hiddo J. L.
dc.contributor.authorRADHAKRISHNAN, Jai
dc.contributor.authorALPERS, Charles E.
dc.contributor.authorBARRATT, Jonathan
dc.contributor.authorBIELER, Stewart
dc.contributor.authorDIVA, Ulysses
dc.contributor.authorINRIG, Jula
dc.contributor.authorKOMERS, Radko
dc.contributor.authorMERCER, Alex
dc.contributor.authorNORONHA, Irene L.
dc.contributor.authorRHEAULT, Michelle N.
dc.contributor.authorROTE, William
dc.contributor.authorROVIN, Brad
dc.contributor.authorTRACHTMAN, Howard
dc.contributor.authorTRIMARCHI, Hernin
dc.contributor.authorWONG, Muh Geot
dc.contributor.authorPERKOVIC, Vlado
dc.contributor.authorPROTECT Investigators
dc.date.accessioned2023-08-16T17:45:40Z
dc.date.available2023-08-16T17:45:40Z
dc.date.issued2023
dc.description.abstractBackground Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety.Methods PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged >= 18 years) with biopsy-proven IgA nephropathy and proteinuria of 1 center dot 0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1 center dot 73 m2 and >= 60 mL/min per 1 center dot 73 m2) and urine protein excretion at screening (<= 1 center dot 75 g/day and >1 center dot 75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein- creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850.Findings Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49 center dot 8%) than the irbesartan group (-15 center dot 1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0 center dot 59; 95% CI 0 center dot 51-0 center dot 69; p<0 center dot 0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups.Interpretation Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.identifier.citationLANCET, v.401, n.10388, p.1584-1594, 2023
dc.identifier.doi10.1016/S0140-6736(23)00569-X
dc.identifier.eissn1474-547X
dc.identifier.issn0140-6736
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/54593
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INCeng
dc.relation.ispartofLancet
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright ELSEVIER SCIENCE INCeng
dc.subject.otherendothelin receptor antagonistseng
dc.subject.otherkidneyeng
dc.subject.otheralbuminuriaeng
dc.subject.otherirbesartaneng
dc.subject.otherexpressioneng
dc.subject.otherefficacyeng
dc.subject.otherdiseaseseng
dc.subject.otherdesigneng
dc.subject.wosMedicine, General & Internaleng
dc.titleSparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active- controlled clinical trialeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countryArgentina
hcfmusp.affiliation.countryAustrália
hcfmusp.affiliation.countrySuécia
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisonl
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisogb
hcfmusp.affiliation.countryisose
hcfmusp.affiliation.countryisoar
hcfmusp.affiliation.countryisoau
hcfmusp.author.externalHEERSPINK, Hiddo J. L.:Univ Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands; Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia; Univ Groningen, Dept Clin Pharm & Pharmacol, NL-9700RB Groningen, Netherlands
hcfmusp.author.externalRADHAKRISHNAN, Jai:Columbia Univ, Div Nephrol, New York, NY USA
hcfmusp.author.externalALPERS, Charles E.:Univ Washington, Dept Lab Med & Pathol, Seattle, WA USA
hcfmusp.author.externalBARRATT, Jonathan:Univ Leicester, Gen Hosp, Dept Cardiovasc Sci, Leicester, England
hcfmusp.author.externalBIELER, Stewart:Travere Therapeut, San Diego, CA USA
hcfmusp.author.externalDIVA, Ulysses:Travere Therapeut, San Diego, CA USA
hcfmusp.author.externalINRIG, Jula:Travere Therapeut, San Diego, CA USA
hcfmusp.author.externalKOMERS, Radko:Travere Therapeut, San Diego, CA USA
hcfmusp.author.externalMERCER, Alex:JAMCO Pharm Consulting, Stockholm, Sweden
hcfmusp.author.externalRHEAULT, Michelle N.:Univ Minnesota, Div Pediat Nephrol, Med Sch, Minneapolis, MN USA
hcfmusp.author.externalROTE, William:Travere Therapeut, San Diego, CA USA
hcfmusp.author.externalROVIN, Brad:Ohio State Univ, Div Nephrol, Wexner Med Ctr, Columbus, OH USA
hcfmusp.author.externalTRACHTMAN, Howard:Univ Michigan, Div Nephrol, Dept Pediat, Ann Arbor, MI USA
hcfmusp.author.externalTRIMARCHI, Hernin:Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia; Hosp Britan Buenos Aires, Nephrol Serv, Buenos Aires, Argentina
hcfmusp.author.externalWONG, Muh Geot:Concord Repatriat Gen Hosp, Dept Renal Med, Concord, NSW, Australia; Univ Sydney, Concord Clin Sch, Concord, NSW, Australia
hcfmusp.author.externalPERKOVIC, Vlado:Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia; Univ New South Wales Sydney, Fac Med & Hlth, Sydney, NSW, Australia
hcfmusp.citation.scopus57
hcfmusp.contributor.author-fmusphcIRENE DE LOURDES NORONHA
hcfmusp.description.beginpage1584
hcfmusp.description.endpage1594
hcfmusp.description.issue10388
hcfmusp.description.volume401
hcfmusp.origemWOS
hcfmusp.origem.pubmed37015244
hcfmusp.origem.scopus2-s2.0-85153340233
hcfmusp.origem.wosWOS:001001276800001
hcfmusp.publisher.cityNEW YORKeng
hcfmusp.publisher.countryUSAeng
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