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  "documentTitle": "Chinook Therapeutics Inc (KDNY)",
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  "notes": "This slide serves as a critique of clinical trial design and reporting practices, specifically regarding the SONAR trial.",
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      "text": "We conclude that the trial data showed that atrasentan is inefficacious for chronic kidney disease.",
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      "text": "We conclude that the trial data showed that atrasentan is inefficacious for chronic kidney disease. The study data shows that there was no statistically significant improvement in advancement to",
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      "text": "SONAR made use of an enrichment-based study design, in which patients were stratified into \"responder\" and \"non-responder\" drug populations following a six-week \"enrichment\" period on atrasentan.",
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      "text": "Only 3,666 patients—the responder population and about 1,000 non-responders—entered the double-blind treatment period, and only 2,648 patients completed the study. As we note supra, the trial was then abruptly halted.",
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      "text": "Patients were required to enter treatment with an angiotensin receptor blocker or an angiotensin-converting enzyme inhibitor and a diuretic, both of which measures were intended to make heart failure less likely and renal repair more likely.",
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      "text": "Patients were excluded from consideration if they had a previous hospital admission for heart failure, a history of pulmonary hypertension, any known non-diabetic kidney disease, a history of severe peripheral or facial oedema, or other-than-normal levels of brain natriuretic peptide (among other criteria).",
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      "text": "Then, all eligible patients were given a six-week round of atrasentan, after which they were stratified into responder and non-responder populations. Responders were those patients who showed a 30% reduction in urine albumin-to-creatinine ratio, who did not have substantial fluid retention, and did not show an increase in serum creatinine during the enrichment period—again, all measures intended to ensure that the population that continued in the trial would be as likely as possible to benefit from the treatment, and as unlikely as possible to suffer cardiovascular complications.",
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      "text": "Despite being designed to reduce the odds of serious adverse effects, the SONAR trial was abruptly halted. We see it as telling that despite the design, the data indicates increased risk of serious cardiovascular events from atrasentan.",
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      "kind": "quote",
      "text": "Atrasentan in patients with diabetes and chronic kidney disease — Vincenzo Sepe, Carmelo Libetta (Lancet January 25, 2020).",
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      "text": "Footnotes 33-43",
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      "text": "Atrasentan: No Structural Repair",
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