Safety and Efficacy of Two Year Spnol and Maximal R Blockad Therapy

• Status: Withdrawn
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

NephroNet proposes to examine whether combining Spironolactone with maximal RAAblockade will further reduce urinary protein at one year and whether prolonged therapy 24 months) is able to slow the decline in GFR. Because of combination MRand RAAS therapsignificantly increases the risk for clinically significantcccc, the investigators also whether the addition of Patironts facilitates the use of combination therapy and allows a larger proportion of diabetic patients the potential benefit of combination therapy on renal function.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: James A. Tumlin, MD; NephroNet, Inc.
• Treatments: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Enalaprilat; Lisinopril; Losartan; Mitogens; Perindopril; Spironolactone; Valsartan

Criteria

Inclusion Criteria:

• Age above 18

• Male or Female

• Patients with Type II diabetes mellitus must be receiving oral agents or insulin injections at the time of randomization

• All eligible patients will be on a stable, maximum tolerated dose of an ACE or ARB for 2 weeks prior to randomization.

• Note: The determination of m tolerated ACE-ARB therapy will be left to the discretion of the site principal investigator

• All eligible patients will have hypertension targetblood pressure of < 140/90mm Hg.

• Antihypertensive therapy may be adjusted to achieve the target blood pressure prior to the time of randomization.

• ACE or ARB therapy will be the primary antihypertensive therapy used for blood pressure control and will be titrated to the highest tolerated dose to achieve a target blood pressure oftarget blood pressure will use antihypertensive agents that have neutral effects on urinary proteinuria (e.g. Hydralazine or long acting Dihydropyridine calcium channel blockers etc.). The final choice of additional medications will be left to the discretion of the site principal investigator (PI)

• Patients with an average urine protein to creatinine (UP/Cr) ratio that is > 500 mg/gm from the average of two historical value within one year prior to randomization will be considered eligible for study entry.

• Patients with a baseline K+ of >5.5 meq/l on maximum tolerated ACE-ARB therapy during the screening period can be treated with 8.4 grams of Patiromer for 7 days. If at the end of 7days the serum K+ is < 5.0 meq/liter the patient will be considered eligible to participate in the study. If at the end of 7 days the serum K+ >5.0 meq/l the dose of Patiromer can be increased to 16.8 grams. If at the end of 7 days the serum K+ is < 5.0 meq/L, the patient will be considered eligible for study entry. If after 7 days at the higher dose of Patiromer the serum K+ >5.0, the patient will be ineligible for study participation.

• Patients with an estimated GFR by CKD-Epi equation1.73 m2

• Female patients will be required to undergo routine birth control measures

Exclusion criteria:

• Estimated GFR by MDRD <20 mls/min/1.73 M2 using the CKD-Epi equation

• Patients with serum K+ > 5.0 meq/l while taking 16.8 gms/day of Patiromer

• Patients with history of Type mellitus

• Patients with HgbA1c > 11%

• Pregnant or breast-feeding female patients

• Female patients unwilling to receive estrogen or progesterone based birth control or are unwilling or unable to use conventional barrier birth control methods.

• Patients with known allergy or intolerance tor Spironolactone therapy

• Patients taking oral or IV digoxin

• Patients receiving chronic steroids > 10 mg/day oral Prednisone

• Patient that do not have minimum of 3 recorded eGFR determinations within 2 years prior to study randomization

• Concurrent use of Amiloride, Triamteren, Aliskerin, or other Aldosterone antagonists Patients receiving any of the above medications will be considered eligible for study participation after a 120week wash-out