{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:00:09Z","timestamp":1791547209164,"version":"4.3.4"},"reference-count":36,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T00:00:00Z","timestamp":1418688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T00:00:00Z","timestamp":1418688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Pyridoxamine dihydrochloride (Pyridorin\u2122) blocks pathogenic oxidative pathways in the progression of diabetic nephropathy. The pyridoxamine pilot study was designed to test entry criteria and outcomes. Subjects had SCr 1.3-3.5 mg\/dl, protein-to-creatinine \u22651,200 mg\/g and used a surrogate outcome of &amp;#x0394;SCr over 52 weeks. Subjects had to be on a maximally tolerated dose of ACE\/ARB for 3 months; stable other antihypertensive doses for 2 months; stable diuretic dose for 2 weeks, and BP \u2264160\/90 mm Hg; or enter a Pharmaco-Stabilization Phase (PSP). This pilot failed to detect an effect on &amp;#x0394;SCr in intent-to-treat analysis. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; We queried the locked clinical trial database for subgroups in which there was a treatment effect. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Subjects not requiring PSP and those with entry SCr &lt;2.0 mg\/dl had a treatment effect. Subjects entering PSP required more changes in antihypertensive medications and experienced larger &amp;#x0394;SCr over 52 weeks. PSP subjects with BP &gt;140\/90 mm Hg had no treatment effect, but those \u2264140\/90 mm Hg did. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Time required for acute effects of ACE\/ARB to stabilize is unknown, but these data suggest &gt;3 months. Thus, subjects in the pivotal trial must be on ACE\/ARB for 6 months. Frequent antihypertensive adjustment could engender SCr changes unrelated to CKD progression. Thus, we will require subjects to have BP \u2264150\/90 mm Hg and on stable antihypertensives for 26 weeks, or \u2264140\/90 mm Hg and on stable antihypertensives for 13 weeks. Since &amp;#x0394;SCr over 52 weeks is limited as a surrogate outcome, the pivotal trial uses a time-to-event analysis of baseline SCr to at least a 50% increase in SCr or ESRD as the primary outcome. This substantial &amp;#x0394;SCr is protected from noise and is clinically relevant. The pyridoxamine pilot provided critical information to inform the design of PIONEER-CSG-17, which we conducted under the SPA agreement with FDA.<\/jats:p>","DOI":"10.1159\/000369310","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T07:57:33Z","timestamp":1418716653000},"page":"22-28","source":"Crossref","is-referenced-by-count":29,"title":["Pyridoxamine Dihydrochloride in Diabetic Nephropathy (PIONEER-CSG-17): Lessons Learned from a Pilot Study"],"prefix":"10.1159","volume":"129","author":[{"given":"Jamie P.","family":"Dwyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kausik","family":"Umanath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Packham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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