Safety and Efficacy of Two Year of RAAS Alone or in Combination With Spironolactone Therapy

NCT ID: NCT03502031

Last Updated: 2022-10-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2024-10-01

Brief Summary

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.

Conditions

Renal Insufficiency, Chronic; Diabetic Nephropathy Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAAS alone

RAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject)

Group Type: ACTIVE_COMPARATOR

Renin-Angiotensin (RAAS) alone

Intervention Type: DRUG

maximal RAAS blockade alone for 24months.

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

Group Type: ACTIVE_COMPARATOR

Renin-Angiotensin (RAAS) blockers in combination with Spironolactone

Intervention Type: DRUG

maximal RAAS blockade alone or in combination with Spironolactone (25 mg) for 24 months.

Interventions

Renin-Angiotensin (RAAS) alone

maximal RAAS blockade alone for 24months.

Intervention Type: DRUG

Renin-Angiotensin (RAAS) blockers in combination with Spironolactone

maximal RAAS blockade alone or in combination with Spironolactone (25 mg) for 24 months.

Intervention Type: DRUG

Other Intervention Names

Lispril, Enalapril, Perindopril, Losarta, Valsar etc.,; Lisinopril, Enalapril, Perindopril, Losartan, Valsartan, or Spironolactone

Eligibility 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 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

• Minimum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nelson Kopyt, MD

UNKNOWN

Sponsor Role: collaborator

James A. Tumlin, MD

OTHER

Sponsor Role: lead

Responsible Party

James A. Tumlin, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Georgia Nephrology Research Institute

Lawrenceville, Georgia, United States

Site Status: RECRUITING

Nelson Kopyt, MD

Bethlehem, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

James A Tumlin, MD

Role: CONTACT

jamestumlinmdnephronet@gmail.com

770-490-9203

Jeremy D Whitson, CCRA

Role: CONTACT

jwhitson@nephrynergy.com

423-943-4265

Facility Contacts

James A Tumlin, MD

Role: primary

jamestumlinmdnephronet@gmail.com

770-490-9203

Jeremy Whitson, CCRA

Role: backup

jwhitson@nephro-synergy.com

423-943-4265

Stephanie Hanzl

Role: primary

shanzl@necresearch.org

610-433-4100 ext. 490

Other Identifiers

NN-01

Identifier Type: -

Identifier Source: org_study_id