2538 Participants Needed

Spironolactone for Kidney Failure

(ACHIEVE Trial)

Recruiting at 155 trial locations
JT
CH
Overseen ByColin Hardy, B.A.
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Population Health Research Institute
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if spironolactone, a pill that blocks a harmful hormone, can reduce heart problems in dialysis patients. These patients are at high risk of heart failure and death, and the pill aims to lower blood pressure and protect their hearts. Spironolactone has been shown to effectively lower blood pressure in patients with resistant hypertension.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking any mineralocorticoid receptor antagonists like spironolactone or eplerenone if you are currently on them and unable to withdraw. Other medications are not specified, so check with the trial coordinators.

What safety data is available for spironolactone in treating kidney failure?

Spironolactone has been studied for safety in various contexts, including heart failure and end-stage renal disease. In heart failure patients, it was generally well tolerated with low frequency of adverse effects related to renal function and potassium levels. In a study with dialysis-dependent patients, spironolactone was found to be safe with similar rates of hyperkalemia and hypotension compared to placebo, although hyperkalemia was more frequent at higher doses (50 mg). Gynecomastia was rare and not significantly different from placebo. Overall, spironolactone appears safe in carefully monitored patients, but hyperkalemia risk increases with higher doses.12345

Is the drug Spironolactone a promising treatment for kidney failure?

Spironolactone shows promise in reducing oxidative stress in kidney transplant patients, which can help improve kidney function. It may also protect against kidney damage during certain medical procedures. These benefits suggest it could be a promising treatment for kidney-related issues.678910

What data supports the idea that the drug Spironolactone for Kidney Failure is an effective treatment?

The available research shows that Spironolactone can reduce oxidative stress in patients who have undergone kidney transplants. In a study, patients who received Spironolactone had less increase in markers of oxidative stress compared to those who received a placebo. This suggests that Spironolactone may help protect the kidneys from damage after a transplant. However, in patients with end-stage renal disease on dialysis, Spironolactone did not show significant improvements in heart-related health, although it was generally safe to use. This indicates that while Spironolactone may be beneficial in certain kidney-related situations, its effectiveness can vary depending on the specific condition.5671112

Who Is on the Research Team?

MW

Michael Walsh, MD, PhD

Principal Investigator

McMaster University

PD

PJ Devereaux, MD, PhD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for adults on dialysis due to kidney failure, who've been receiving treatment for at least 90 days. It's open to those aged 45 and above or adults over 18 with diabetes. Participants must not be pregnant, breastfeeding, have high potassium levels, known allergies to spironolactone, or be in another similar drug trial.

Inclusion Criteria

I am at least 45 years old or I am 18 or older with diabetes.
Provides informed consent
I am on dialysis, either hemodialysis twice a week or peritoneal dialysis daily.
See 2 more

Exclusion Criteria

My doctor says I must or must not take spironolactone.
I am currently on a medication like spironolactone or eplerenone and cannot stop.
Current or planned pregnancy or breastfeeding
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either spironolactone or placebo to evaluate its effect on reducing cardiac mortality and hospitalizations for heart failure in dialysis patients

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

  • Placebo Oral Tablet
  • Spironolactone
Trial Overview The study tests if Spironolactone can reduce heart failure and related deaths in patients on dialysis. Half of the participants will receive Spironolactone while the other half will get a placebo (a pill with no active drug), to compare outcomes between the two groups.
How Is the Trial Designed?
2Treatment groups
Active Control
Placebo Group
Group I: Spironolactone 25 MG TabletActive Control1 Intervention
25 mg of active spironolactone in tablet form
Group II: Placebo Oral TabletPlacebo Group1 Intervention
A tablet with no active medication that will be an exact match of the active spironolactone in taste and appearance

Spironolactone is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Aldactone for:
  • High blood pressure
  • Heart failure
  • Liver scarring
  • Kidney disease
  • Low blood potassium
  • Early puberty in boys
  • Acne
  • Excessive hair growth in women
🇪🇺
Approved in European Union as Aldactone for:
  • Fluid retention due to heart failure
  • Liver scarring
  • Kidney disease
  • High blood pressure
  • Low blood potassium

Find a Clinic Near You

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials
165
Recruited
717,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials
1,417
Recruited
26,550,000+

Published Research Related to This Trial

Spirolactones, such as spironolactone and K+ canrenoate, inhibit the binding of the androgen 5alpha-dihydrotestosterone (DHT) to its receptors in the prostate, suggesting a mechanism for their antiandrogenic effects.
The study indicates that spirolactones exert their antiandrogenic activity primarily through peripheral antagonism of androgens rather than affecting the production of testosterone or inhibiting prostatic 5alpha-reductase activity.
Antiandrogenic effect of spirolactones: mechanism of action.Corvol, P., Michaud, A., Menard, J., et al.[2022]
In a study of 129 maintenance hemodialysis patients over 36 weeks, spironolactone was found to be safe with no significant increase in hyperkalemia or hypotension compared to placebo, although higher doses (50 mg) did show a greater risk of hyperkalemia.
Despite its safety, spironolactone did not demonstrate any significant improvement in cardiovascular function or diastolic parameters compared to placebo, suggesting limited efficacy in this patient population.
Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial.Charytan, DM., Himmelfarb, J., Ikizler, TA., et al.[2021]
SC 23992 is a new spirolactone that shows two to eight times greater potency as an anti-aldosterone agent in vivo compared to Aldactone, although it has only about 10% potency in vitro.
This new compound may offer a safer alternative for patients, as it appears to have fewer antiandrogen side effects compared to traditional treatments.
SC 23992: radioreceptor assays for therapeutic and side effects.Funder, JW., Mercer, J., Hood, J.[2019]

Citations

Antiandrogenic effect of spirolactones: mechanism of action. [2022]
Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. [2021]
SC 23992: radioreceptor assays for therapeutic and side effects. [2019]
Spironolactone reduces oxidative stress in living donor kidney transplantation: a randomized controlled trial. [2020]
The Effect of Spironolactone on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Catheterization: Study Design and Rationale. [2020]
How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? [2019]
Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones. [2019]
SC 25152: A potent mineralocorticoid antagonist with reduced affinity for the 5 alpha-dihydrotestosterone receptor of human and rat prostate. [2013]
Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Spironolactone use in heart failure patients with end-stage renal disease on hemodialysis: is it safe? [2023]
Is spironolactone safe for dialysis patients? [2019]
The safety of spironolactone treatment in patients with heart failure. [2019]
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