Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Add-On

NCT03597035 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 02-17-16
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Patiromer add-on to a mineralocorticoid receptor antagonist (MRA) in patients with Type 2 diabetes mellitus and chronic kidney disease (CKD) will reduce blood pressure and left ventricular (LV) mass to a greater extent compared to patients with MRA alone and favorably affect key secondary hemodynamic and inflammatory variables including atherosclerosis progression. Atherosclerosis is the leading cause of morbidity and mortality in Type II diabetes. A cell type called the monocyte/macrophage is critical to development and complications of atherosclerosis. This project will evaluate the effectiveness of a medication called Spironolactone in addition to Patiromer in preventing atherosclerosis in Type II diabetes through its effects on cells such as the monocyte. Spironolactone has been demonstrated to be effective for the treatment of patients after a heart attack and stroke. The investigators will evaluate the impact of Spironolactone in combination with Patiromer in reducing atherosclerosis plaque and additionally evaluate its potential in changing inflammation. The investigators envision that a strategy of simultaneously probing effect of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design hard event (heart attack, stroke etc.) based trials.

Conditions

Type2 Diabetes; Hyperkalemia

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Mass

  Change in left ventricular mass from baseline to 12 months.

  Time 0: study baseline, beginning of treatment. Time 1: 12 months follow-up, end of treatment.

Study Arms (1)

Patiromer Add-On

EXPERIMENTAL

Single arm experimental study in 50 diabetic patients with chronic kidney disease and hyperkalemia.

Drug: Spironolactone

Interventions

Spironolactone DRUG

The study participants will receive concomitant treatment with Veltassa 8.4 grams per day and Spironolactone 25 mg per day or maximum tolerated dose. If dictated by the potassium level, Veltassa can be increased to 16.8 grams per day.

Also known as: Veltassa

Patiromer Add-On

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients \>= 45 years and able to provide informed consent (females must be either post-menopausal for one year, surgically sterile, or using effective contraception. Oral contraceptives are disallowed.)
• Patients with type II diabetes with HbA1c ≤ 9.0 on stable anti-glycemic regimen that may include oral and/or injectable therapy (GLP-1/Insulin etc.). Changes in dose of glycemic regimen is allowed during the course of the trial if felt to be clinically appropriate.
• Glomerular filtration rate (GFR) \<90 and evidence of proteinuria (Urine Albumin/Creatinine Ratio of \>30 mg/g or equivalent) in a urine specimen within 12 months OR GFR \<60 mg/g regardless of proteinuria
• Patients must be on angiotensin-converting-enzyme inhibitor (ACE) and/or angiotensin-resistance-blocker (ARB) therapy with no planned dose adjustments.
• Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).

You may not qualify if:

• Uncontrolled hypertension (Systolic Blood Pressure (SBP)\>160 and/or Diastolic Blood Pressure (DBP)\>95 mmHg at visit 0 (screening) and SBP \>145 mm Hg at visit 2).
• GFR (MDRD) of \<20 at visit 0 (screening)
• Hyperkalemia defined as serum K+ \<5.1 meq/L at visit 0 (screening).
• LDL cholesterol \>150 mg/dL
• Plasma triglycerides \> 400 mg/dl
• Contraindications to MRI (metallic implants, severe claustrophobia).
• Acute coronary syndrome, Transient ischemic attack, cardiovascular accident (CVA) or critical limb ischemia during the last 6 months or coronary/peripheral revascularization within the last 3 months.
• Evidence of a secondary form of hypertension.
• Initiation of new therapy with statins, ACE/ARB, antioxidants, calcium channel blockers (CCBs), diuretics, β blockers.
• Type I diabetes mellitus
• Known contraindication, including history of allergy to Spironolactone or Patiromer
• Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant)
• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
• Significant hyponatremia defined as Na \<130 meq/L.
• History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and cured prostate cancer).

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Relypsa, Inc.: collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Hyperkalemia

Interventions

Spironolactone; patiromer

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Sanjay Rajagopalan
• Organization: University Hospitals Cleveland Medical Center

Sanjay.Rajagopalan@UHhospitals.org

216-844-5125

Study Officials

• Sanjay Rajagopalan, MBBS

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: An open label proof-of-concept clinical trial in 50 patients with Type II diabetes evaluating the effects of MRA + Patiromer on LV mass and plaque regression over 12 months of treatment by magnetic resonance imaging (MRI).

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: July 24, 2018
• Study Start: July 17, 2018
• Primary Completion: July 23, 2020
• Study Completion: July 31, 2020
• Last Updated: May 16, 2022
• Results First Posted: May 16, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)