Cabel, Felix didn't say that it was non-significant. He said it was marginally significant. However, he did incorrectly state p=0.4. It was actually p=0.04 vs. baseline for the apabetalone group.

Iconoclast, I agree with your statement about the low number of placebo patients affecting the ability to detect statistical significance for both placebo vs. baseline as well as apabetalone vs. placebo changes. 

Keep in mind that SUSTAIN and ASSURE were never designed or powered to be CKD trials assessing eGFR. That finding only came out in post-hoc analysis. If you look at the ASSURE and SUSTAIN exclusion criteria, they actually tried to avoid recruiting patients with renal impairment.

ASSURE exclusion criteria: "Evidence of renal impairment as determined by any one of the following: serum creatinine >1.5 mg/dL (>133 micromol/L) by central lab at Visit 1, a calculated creatinine clearance less than 60 ml/min at Visit 1, a history of dialysis, a history of nephrotic syndrome."

SUSTAIN exclusion criteria: "Evidence of renal impairment as determined by any one of the following: serum creatinine >1.5 mg/dL (>133 micromol/L) at screening Visit 1, a history of dialysis, a history of nephritic syndrome."

Those 48 patients for the post-hoc study kind of snuck in unintentionally. I don't think renal function was even on Resverlogix's radar until the post-hoc analyses of SUSTAIN and ASSURE, so you can't really blame them for not designing a better CKD-centered trial in SUSTAIN and/or ASSURE when the primary focus then was on apo-AI, HDL, reverse cholesterol transport and plaque reduction! Hindsight is always 20/20!

The CKD sub-study of BETonMACE is larger, longer and pre-specified. So with greater than 100 patients in each group (placebo or apabetalone) treated for an average of about 2 years, this greatly improves their chances of detecting a statistically significant difference in eGFR change both vs. baseline and between groups. The apabetalone drug may elicit continued eGFR improvement with longer dosing, and conversely the placebo pateints may continue with their eGFR decline with continued dosing.

The recent excitement about the CREDENCE trial for the SGLT2 inhibitor canagliflozin on renal function is a testament to the dire need for drugs to improve renal function in diabetics. Canagliflozin only slowed the decline of eGFR vs. placebo, but did not improve it, and this garned huge attention and headlines!

BearDownAZ