Safety and Efficacy of Two Year of RAAS Alone or in Combination With Spironolactone Therapy (MRA-ACE)

October 27, 2022 updated by: James A. Tumlin, MD

Safety and Efficacy of Maximally Tolerated RAAS Blockade and Spironolactone Therapy on Urinary Proteinuria and Progression of Type II Diabetic Nephropathy in African Americans and Other Patient Cohorts.

NephroNet proposes to examine whether combining Spironolactone with maximal RAAS blockade 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 MRA and RAAS therapy significantly increases the risk for clinically significant hyperkalemia, we also plan to determine whether the addition of Patiromer to these patients facilitates the use of combination therapy and allows a larger proportion of diabetic patients the potential benefit of combination therapy on renal function.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

72

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Georgia
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Recruiting
        • Nelson Kopyt, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

75 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 to 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 princ
  • All eligible patientswill have hypertension targetblood pressur of < 140/90mm Hg.
  • Antihypertensiv 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 titrthe highest tolerated dose to achieve a target blood pressure of <Patients requiring additional medications to achieve the target blood pressure will use antihypertensive agents that have neutral effects on urinary proteinuria (e.g. Hydralazine or lo Dihydropyridine calcium channel blockers etc.). CcThe final choice of additional medications will be left to the discretion of the site principal investigator (PI)
  • Patients with anurine protein to creatinine (UP/Cr) ratio that is 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. X5 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 CK-Epi .73 m2
  • Female patients will be required to undergo routine birth control measures

Exclusion criteria:

  • Estimated GFR by MDRD20 mls/min/1.73 M2 using the CKD-Epi equation
  • Patients with serum K+ > 5.00 while taking 16.8/day of Patiromer
  • Patients with history of Type mellitus
  • Patients with HgbA
  • Pregnant or breast-feeding female patients
  • Female patients unwilling to receive estrogen or progesterone based birth control or are unwilling or unable to usconventional barrier birth control methods.
  • Patients with known allergy or intolerance tor Spironolactone therapy
  • Patients taking oral or IV digoxin
  • Patients receiving chronic steroids > 1oral Prednisone
  • Patient that do nohave minimum o eGFR determinations within 2 years prior to study randomization
  • Concurrent use of Amiloride, , Aliskerin, or other Aldosterone antagonists Patien receiving any of the above medications will be considered eligible for study participation after a wash-out

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: RAAS alone
RAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject)
Drug: Renin-Angiotensin (RAAS) alone
maximal RAAS blockade alone for 24months.
Other Names:
  • Lispril, Enalapril, Perindopril, Losarta, Valsar etc.,
Active Comparator: RAAS in Combination with Spironolactone
RAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject); Spironolactone taken each day at 25mg
Drug: Renin-Angiotensin (RAAS) blockers in combination with Spironolactone
maximal RAAS blockade alone or in combination with Spironolactone (25 mg) for 24 months.
Other Names:
  • Lisinopril, Enalapril, Perindopril, Losartan, Valsartan, or Spironolactone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combination Therapy - RAAS inhibition and Spironolactone to lower UP/Cr
Time Frame: 24 months
To determine whether combination therapy with maximall RAAS inhibition and Spironolactone is superior to RAAS inhibition alone in lowering the UP/Cr ratio at 12 months
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combination Therapy - RAAS inhibition and Spironolactone
Time Frame: 24 months
To determine whether combination therapy with maximally tolerated RAAS inhibition and Spironolactone is superior to RAAS inhibition alone in slowing the progression of renal disease as evidenced by changes in GFR
24 months
Combination Therapy - RAAS inhibition and Spironolactone that develop hyperkalemia
Time Frame: 12 months, 24 months
To determine the patients in the maximal RAAS blockade group and those receiving combination RAAS + Spironolactone therapy developing clinically significant hyperkalemia as defined as a serum K+ level greater than 5.5 meq/L. We will determine the percentage of patients that require "Patiromer-Rescue" for K+ > 5.5 meq/L and the percentage of patients maintained with serum K+ less than 5.5 meq/L
12 months, 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

James A. Tumlin, MD

Collaborators

Nelson Kopyt, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2018

Primary Completion (Actual)

October 1, 2022

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

November 13, 2017

First Submitted That Met QC Criteria

April 10, 2018

First Posted (Actual)

April 18, 2018

Study Record Updates

Last Update Posted (Actual)

October 28, 2022

Last Update Submitted That Met QC Criteria

October 27, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NN-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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