Clinical trial NCT00106561: Using the Drug Spironolactone to Test If It Reduces Protein Leakage From the Kidney
Official title: A Double-Blind, Placebo-Controlled Study on the Effect of Spironolactone, in Patients With Persistent Proteinuria on Long-Term Angiotensin Converting Enzyme Inhibitor Therapy, With or With Out an Angiotensin II Receptor Blocker
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Kidney Disease
Diabetic Nephropathy
Glomerulonephritis
Proteinuria
Keywords: spironolactone
proteinuria
angiotensin converting enzyme inhibitor
angiotensin receptor blocker
renin angiotensin aldosterone system
aldosterone
Lead sponsor: Melbourne Health
Sponsor class: OTHER
First posted: 2005-03-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine which combination of the tablets ramipril, irbesartan or spironolactone is best to lower protein leakage from the kidney.

Detailed description: Protein leak from the kidney into the urine is an indicator of kidney damage. The higher the leak, the worse the damage and the more likely the patient will lose their kidney function long term. Interventions that lower protein leak make the kidneys last longer.

There are 2 groups of medications, both blood pressure tablets, the ACEI (angiotensin converting enzyme inhibitors) and ATRB (angiotensin receptor blockers) which have shown to reduce the amount of protein leaking from the kidney and as a result lengthen the life of the kidney. There has also been evidence that using these 2 tablets in combination is better than using either one alone. In spite of these tablets, there still remain some patients that continue to leak protein in the urine.

Recently there has been evidence that the tablet spironolactone, which is a fluid tablet, also reduces protein leakage from the kidney. In this study we look at various combinations of these tablets to see which works best to lower protein leakage from the kidney.

Patients are divided into 4 groups. Each group will receive the tablet ramipril (an ACEI). In group 1, patients will be on ramipril and 2 blank tablets, group 2 will be on ramipril, irbesartan (an ATRB) and a blank tablet, group 3 will be on ramipril, spironolactone and a blank tablet and group 4 will be on ramipril, irbesartan and spironolactone. Protein leakage is measured at the beginning and after 3 months of treatment.

Eligibility criteria: Inclusion Criteria:

* Proteinuria more than 1.5 g/day
* On ACEI for more than 6 months
* Serum creatinine less than 200 micromol/L with less than 20% variability in the preceeding 3 months
* Creatinine clearance more than 30 ml/min, with less than 20% variability in the preceeding 3 months

Exclusion Criteria:

* Serum potassium level more than 5 mmol/L
* Treatment with corticosteroids, NSAID or immunosuppressant medication
* Acute myocardial infarction or cerebrovascular accident in the previous 6 months
* Severe uncontrolled hypertension (diastolic \> 115 mmHg or systolic BP \[blood pressure\] \> 220 mmHg)
* Evidence or suspicion of renovascular disease, obstructive uropathy, collagen disease, cancer, drug or alcohol abuse, pregnancy, or breast feeding and ineffective contraception

Primary outcomes:
measure: percent reduction in 24 hour urine protein excretion
Secondary outcomes:
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Department of Nephrology, The Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Director Department of Nephrology, The Royal Melbourne Hospital
name: Gavin G Becker, MBBS MD
role: STUDY_DIRECTOR
References:
citation: Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med. 2001 Sep 20;345(12):925-6. doi: 10.1056/NEJM200109203451215. No abstract available.
citation: Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.