Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)

University of Michigan

Status and phase: Withdrawn; Phase 4

Conditions: Hypertension

Treatments: Drug: Eplerenone 50mg; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04746495

1K23HL128909-01A1 (U.S. NIH Grant/Contract)

HUM00170418

Details and patient eligibility

About

This blinded cross-over clinical trial will enroll participants with mild stage 1 hypertension to evaluate whether urinary extracellular transcript abundance predicts response to an mineralocorticoid receptor (MR) antagonist, eplerenone.

Eligible participants will have a 2 week wash-in period followed by 4 weeks of treatment with placebo or eplerenone. There will be a 2 week wash out period from study medications and then participants will take the other drug (placebo or eplerenone) for 4 weeks. In addition, participants will also provide urine and blood samples during the trial, have physical assessments, and be monitored for safety.

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• History of mild stage 1 systemic hypertension as defined by:

  1. Systolic blood pressure (SBP) ≥ 140 millimeters of Mercury (mmHg) or diastolic blood pressure (DBP) ≥ 90 mmHg on 2 occasions and

  2. Treatment with 1-2 antihypertensive medications (stable dose for 6 weeks)

     Exclusion Criteria:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.

• Stage 2 hypertension (history of blood pressure ≥ 160/100 mmHg)

• History of hypertensive urgency, hypertensive crisis, or hospitalizations for hypertension

• Current mineralocorticoid antagonist use

• Type II Diabetes with microalbuminuria

• Primary adrenal insufficiency

• Current glucocorticoid use

• Electrolyte abnormality on baseline laboratory assessment

• Current potassium supplementation

• Positive test for leukocyte esterase on urinalysis

• Creatinine clearance < 50 mL/min on baseline laboratory assessment

• Hyperkalemia

• Potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene)

• Serum potassium >5.0 milliequivalents per liter (mEq/L) on baseline laboratory assessment

• Current use of strong CYP3A4 inhibitors (some include: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir).

• Serum creatinine > 1.5 mg/dL in males on baseline laboratory assessment

• Serum creatinine > 1.3 mg/dL in females

• Current beta blocker use

• Any other condition thought by the Principal Investigator to place the participant at increased risk of injury during the clinical trial or compromise the scientific integrity of the study

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive 4 weeks of placebo and then 4 weeks of Eplerenone.

Treatment:

Drug: Placebo

Eplerenone

Experimental group

Description:

Participants will be randomized to receive 4 weeks of Eplerenone and then 4 weeks of Placebo.

Treatment:

Drug: Eplerenone 50mg