1 / 10

Givertz et al. J Am Coll Cardiol 2007;50:1551-60

The Effects of KW-3902, an Adenosine A 1 -Receptor Antagonist, on Diuresis and Renal Function in Patients with Acute Decompensated Heart Failure and Renal Impairment or Diuretic Resistance. Givertz et al. J Am Coll Cardiol 2007;50:1551-60.

helena
Download Presentation

Givertz et al. J Am Coll Cardiol 2007;50:1551-60

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. The Effects of KW-3902, an Adenosine A1-Receptor Antagonist, on Diuresis and Renal Function in Patients with Acute Decompensated Heart Failure and Renal Impairment or Diuretic Resistance Givertz et al. J Am Coll Cardiol 2007;50:1551-60 Michael M. Givertz, MD, FACC, Barry M. Massie, MD, FACC, Tara K. Fields, Leeanne L. Pearson, RN, BS, and Howard C. Dittrich, MD, FACC, on behalf of the CKI-201 and CKI-202 Investigators

  2. Background and Objectives • Intravenous loop diuretics are the mainstay of therapy for patients with acute decompensated heart failure (ADHF). Treatment, however, may be complicated by diuretic resistance and/or worsening renal function. • We sought to evaluate the dose-dependent effects of adenosine A1-receptor blockade on diuresis and renal function in patients with acute decompensated heart failure (ADHF) and renal impairment or diuretic resistance.

  3. Methods • We carried out a pair of randomized, double-blind, placebo controlled, proof-of-concept studies in two clinically challenging ADHF populations. • CKI-201: Hospitalized acute decompensated heart failure patients with renal impairment • CKI-202: Patients refractory to high doses of conventional diuretics

  4. CKI-201 Protocol • Double-blind, randomized Rx with placebo or one of 4 doses of KW-3902 (2.5 mg, 15 mg, 30 mg, 60 mg) • 146 subjects, morning 2 hr infusion for up to 3 days • First 6 hours (Day 1 only) KW-3902 or placebo given as monotherapy (diuretics held for 12 hours) • Primary endpoint: 6 hour urine volume • IV loop diuretics given as indicated after 6 hours • KW-3902 or placebo administered in assigned dose on Days 2 and 3, simultaneous with furosemide as needed • Final efficacy measures on day of discharge or Day 4, whichever came first

  5. CKI-201 Cumulative Urine Volume Cumulative urine volume (mean  SEM) 6 hours after initiation of placebo or KW-3902 in ADHF patients with renal impairment (*P = 0.02 vs. placebo).

  6. CKI-201 Furosemide Administration Daily dose of IV furosemide (mean  SEM) administered to the placebo and four KW-3902 groups over the first 3 days of the study (*P < 0.05 vs. placebo).

  7. CKI-202 Protocol • Randomized, double-blind, placebo controlled, dose escalation, exploratory study • 35 subjects: 23 active in three escalating dose groups (10 mg, 30 mg and 60 mg) and 12 placebo • 3-5 hour baseline period: diuretics withheld and baseline hourly urine volume and creatinine clearance established • 2-3 hour infusion of KW-3902 or placebo • Rescue IV furosemide allowed after study drug • Efficacy measures through 24 hours and safety measures through 48 hours • Primary endpoint: change in hourly urine volume

  8. CKI-202 Hourly Urine Volume Change in hourly urine volume (mean  SEM) through 24 hours post-dosing with placebo or KW-3902 in ADHF patients refractory/resistant to diuretics.

  9. CKI-202 Creatinine Clearance Change in measured creatinine clearance (mean  SEM) relative to baseline in ADHF patients refractory/resistant to diuretics (*P < 0.05 vs. baseline).

  10. Conclusion In patients with acute decompensated heart failure and volume overload, KW-3902, an adenosine A1-receptor antagonist, enhances the response to loop diuretics and may have a renal protective effect.

More Related