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Article: Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease

TitlePost hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease
Authors
Keywordsanalgesics
atrasentan
chronic kidney disease
diabetes
nonsteroidal anti-inflammatory drug
opioids
pain
Issue Date1-Dec-2023
PublisherElsevier
Citation
Kidney International, 2023, v. 104, n. 6, p. 1219-1226 How to Cite?
Abstract

Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25–75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300–5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72–0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71–0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60–0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.


Persistent Identifierhttp://hdl.handle.net/10722/337518
ISSN
2023 Impact Factor: 14.8
2023 SCImago Journal Rankings: 3.886
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, KW-
dc.contributor.authorSmeijer, JD-
dc.contributor.authorSchechter, M-
dc.contributor.authorJongs, N-
dc.contributor.authorVart, P-
dc.contributor.authorKohan, DE-
dc.contributor.authorGansevoort, RT-
dc.contributor.authorLiew, A-
dc.contributor.authorTang, SCW-
dc.contributor.authorWanner, C-
dc.contributor.authorDe Zeeuw, D-
dc.contributor.authorHeerspink, HJL-
dc.date.accessioned2024-03-11T10:21:31Z-
dc.date.available2024-03-11T10:21:31Z-
dc.date.issued2023-12-01-
dc.identifier.citationKidney International, 2023, v. 104, n. 6, p. 1219-1226-
dc.identifier.issn0085-2538-
dc.identifier.urihttp://hdl.handle.net/10722/337518-
dc.description.abstract<p>Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25–75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300–5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72–0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71–0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60–0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.</p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofKidney International-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectanalgesics-
dc.subjectatrasentan-
dc.subjectchronic kidney disease-
dc.subjectdiabetes-
dc.subjectnonsteroidal anti-inflammatory drug-
dc.subjectopioids-
dc.subjectpain-
dc.titlePost hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease-
dc.typeArticle-
dc.identifier.doi10.1016/j.kint.2023.08.014-
dc.identifier.scopuseid_2-s2.0-85173166574-
dc.identifier.volume104-
dc.identifier.issue6-
dc.identifier.spage1219-
dc.identifier.epage1226-
dc.identifier.eissn1523-1755-
dc.identifier.isiWOS:001115449200001-
dc.identifier.issnl0085-2538-

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