Eplerenone in Hemodialysis Trial (PHASE)

Pilot Trial of Hemodialysis Patient Aldosterone antagoniSm With Eplerenone Trial

Forty percent of patients that require dialysis for kidney failure die within three years mostly due to heart disease. Heart failure and high blood pressure are common problems in patients that require dialysis and are key causes of death due to heart disease. Eplerenone is a drug that is very effective at improving heart failure and reducing blood pressure in patients that do not require dialysis. There is currently no evidence to tell physicians whether eplerenone would have similar benefits in patients that require dialysis. This evidence can only be reliably generated by performing a large scale study. Before such a study is undertaken, the investigators must determine whether eplerenone will be well tolerated and safe in patients that require dialysis. The investigators will perform an initial small trial called the Pilot trial in Hemodialysis patients undergoing Aldosterone antagoniSm with Eplerenone (PHASE) to determine if eplerenone is a well tolerated, safe medication to use in a very large, global study that will show whether or not eplerenone reduces important outcomes for patients like death from heart causes.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; End Stage Renal Disease
• Intervention / Treatment: Drug: Placebo; Drug: eplerenone

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • St. Joseph's Healthcare
    • London, Ontario, Canada
    • Toronto, Ontario, Canada
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• On hemodialysis >90 days
• Prescribed target body weight within 1 kg of current for all dialysis sessions within 4 weeks prior to randomization
• Able to provide written informed consent to participate

Exclusion Criteria:

• Occurrence of documented clinically important hypotension (systolic blood pressure <90 that required treatment) within 4 weeks of randomization
• Change in blood pressure medications within 4 weeks prior to randomization
• Occurrence of pre-dialysis serum potassium >6.0 mmol/L in 4 weeks prior to randomization
• Currently treated with and cannot withdraw spironolactone or eplerenone due to medical necessity
• Known allergy or sensitivity to eplerenone
• Pregnancy
• Scheduled living related donor renal transplant within the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Placebo
Experimental: Eplerenone; Target of 50 mg/day	Drug: eplerenone; target 50 mg per day titrated down for hyperkalemia or hypotension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
permanent discontinuation of the study medication for hyperkalemia or permanent discontinuation of the study medication for hyperkalemia or hypotension	13 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
permanent discontinuation of study drug for any reason	13 weeks
treatment adherence	13 weeks
pre-dialysis potassium	13 weeks
frequency of serious adverse events	13 weeks
frequency of hospitalizations for a vascular reason	13 weeks
fatal and non-fatal vascular events	13 weeks

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Michael Walsh, McMaster University, Population Health Research Institute, St. Joseph's Hospital; Principal Investigator: Ron Wald, Keenan Research Centre, St. Michael's Hospital, University of Toronto

Publications and helpful links

General Publications

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 23, 2012
• First Submitted That Met QC Criteria: July 24, 2012
• First Posted (Estimate): July 25, 2012

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 24, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: PHASE-1