Abstract: FR-PO1078
Safety and Cardiovascular Efficacy of Spironolactone (SPL) in Dialysis-Dependent ESRD (SPin-D): A Pilot Trial of the NIDDK Hemodialysis Novel Therapies Consortium
Session Information
- Late-Breaking Clinical Trial Posters
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Dialysis
- 606 Dialysis: Epidemiology, Outcomes, Clinical Trials - Cardiovascular
Authors
- Charytan, David M., Brigham and Women's Hospital/Harvard Medical School, Brookline, Massachusetts, United States
- Himmelfarb, Jonathan, Kidney Research Institute, Seattle, Washington, United States
- Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
- Hsu, Jesse Yenchih, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Landis, J. Richard, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
- Kusek, John W., NIDDK, Bethesda, Maryland, United States
- Kliger, Alan S., Yale New Haven Health System, New Haven, Connecticut, United States
- Dember, Laura M., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
Background
Small trials suggest that SPL reduces cardiovascular events in maintenance hemodialysis patients but the optimal dose for a large, clinical outcomes trial is unknown.
Methods
Multicenter, randomized, double-blind placebo(PL)-controlled trial of SPL at 12.5, 25, or 50 mg per day for 36 weeks for patients receiving maintenance hemodialysis. The trial aimed to evaluate safety (primary) and generate estimates of efficacy on cardiac structure and function. Randomization was based on a 2:1 ratio for PL vs each SPL dose.
Results
129 patients were randomized. Hyperkalemia and hypotension events were more frequent with SPL 50 mg/day than with lower doses, but did not result in more frequent study drug reduction or discontinuation than PL (Table). There were no differences in change from baseline to week 36 in the primary efficacy measure of diastolic function.
Conclusion
SPL appears to be reasonably safe at doses ranging from 12.5 to 50 mg per day in a clinical trial setting with regular monitoring. The greater rate of hyperkalemia at 50 mg suggests that safety measures such as dose titration/reduction algorithms should be incorporated in a clinical outcomes trial if a 50 mg dose is used.
Safety Outcomes
| Placebo N=51 | SPL 12.5 mg N=27 | SPL 25 mg N=26 | SPL 50 mg N=25 | P value for trend | P value SPL vs Placebo | |
| Primary | ||||||
| K >6.5 mEq/L, # per 100 pt-wk | 1.20 | 0.71 | 0.55 | 2.42 | 0.08 | 0.90 |
| Serious hypotension1, # per 100 pt-wk | 0 | 0.30 | 0 | 0.30 | NE6 | NE6 |
| Secondary | ||||||
| Serious hyperkalemia2, # per 100 pt-wk | 0.30 | 0.20 | 0 | 1.51 | NE6 | 0.16 |
| K >6.0 mEq/L, # per 100 pt-wk | 3.50 | 2.12 | 2.18 | 5.04 | 0.08 | 0.50 |
| Per-patient K, mEq/L, mean (SD) | 4.84 (0.50) | 4.85 (0.44) | 4.76 (0.43) | 4.96 (0.43) | 0.47 | 0.84 |
| Recurrent intra-dialytic hypotension3, # per 100 pt-wk | 4.14 | 3.94 | 4.25 | 6.75 | 0.01 | 0.17 |
| Inter-dialytic hypotension4, # per 100 pt-wk | 0.85 | 0.81 | 0.87 | 0.91 | 0.59 | 0.73 |
| Study drug reduction or discontinuation, # (%) | 15 (29.4) | 4 (14.8) | 6 (23.1) | 8 (32.0) | 0.60 | 0.42 |
| Death5,,# (%) | 2 (3.9) | 0 | 2 (7.7) | 1 (4.0) | NE6 | >0.99 |
1Requiring hospitalization or ER visit. 2Requiring hospitalization, extra dialysis, or resin. 3Systolic bp<80 or treatment for hypotension during 3 dialysis sessions within 30 days. 4Systolic bp <90 or change in bp medication for hypotension between dialysis sessions. 5No deaths due to hyperkalemia. 6Non-estimable due to 0 values in ≥1 group.
Funding
- NIDDK Support