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

NCT03502031 | Unknown Phase 4 FDA Drug

• 1 other identifier: NN-01
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Combination Therapy - RAAS inhibition and Spironolactone to lower UP/Cr

  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 Outcomes (2)

• Combination Therapy - RAAS inhibition and Spironolactone

  24 months

• Combination Therapy - RAAS inhibition and Spironolactone that develop hyperkalemia

  12 months, 24 months

Study Arms (2)

RAAS alone

ACTIVE COMPARATOR

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

RAAS in Combination with Spironolactone

ACTIVE COMPARATOR

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

Interventions

Renin-Angiotensin (RAAS) alone DRUG

maximal RAAS blockade alone for 24months.

Also known as: Lispril, Enalapril, Perindopril, Losarta, Valsar etc.,

RAAS alone

Renin-Angiotensin (RAAS) blockers in combination with Spironolactone DRUG

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

Also known as: Lisinopril, Enalapril, Perindopril, Losartan, Valsartan, or Spironolactone

RAAS in Combination with Spironolactone

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• James A. Tumlin, MD: lead
• Nelson Kopyt, MD: collaborator

Study Sites (2)

Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

RECRUITING

Nelson Kopyt, MD

Bethlehem, Pennsylvania, 18017, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Single Person; Enalapril; Perindopril; Spironolactone; Lisinopril; Losartan; Valsartan

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Essential

Central Study Contacts

James A Tumlin, MD

CONTACT

770-490-9203; jamestumlinmdnephronet@gmail.com

Jeremy D Whitson, CCRA

CONTACT

423-943-4265; jwhitson@nephrynergy.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: April 18, 2018
• Study Start: October 1, 2018
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2024
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)