Early Mineralocorticoid Receptor Antagonist Therapy for Low-Renin Essential Hypertension (EMERALD)
Early Mineralocorticoid Receptor Antagonist Therapy for Low-Renin Essential Hypertension: A Randomized Controlled Study
This study aims to evaluate the efficacy and safety of early initiation of eplerenone, a second-generation mineralocorticoid receptor antagonist, compared with standard antihypertensive treatment in adults with low-renin essential hypertension. The study will assess whether an eplerenone-based treatment strategy provides greater blood pressure reduction, improves blood pressure control, and reduces antihypertensive medication burden compared with standard treatment.
Studie Overzicht
Toestand
Toestand
Conditie
Conditie
Interventie / Behandeling
Interventie / Behandeling
Gedetailleerde beschrijving
The EMERALD Trial is a prospective, randomized, open-label, controlled study designed to compare the efficacy and safety of early initiation of a second-generation mineralocorticoid receptor antagonist with standard antihypertensive treatment in adults with low-renin essential hypertension.
A total of 128 eligible participants will be enrolled and randomly assigned in a 1:1 ratio to either an intervention group or a control group.
In the intervention group, participants will receive an eplerenone-based treatment strategy, starting with eplerenone 50 mg once daily. The dose may be gradually increased to 50 mg twice daily, and additional antihypertensive medications may be added according to blood pressure response and treatment tolerability.
In the control group, participants will receive standard antihypertensive treatment based on current clinical guidelines and routine practice. Medication doses may be gradually increased or treatment regimens adjusted according to blood pressure response and treatment tolerability.
In both groups, treatment will be adjusted to achieve an office seated blood pressure below 140/90 mmHg.
Participants will be followed for 24 weeks, with scheduled clinic visits at baseline and weeks 4, 12, and 24, supplemented by remote follow-up between visits.
The primary outcome is the change in mean daytime systolic blood pressure from baseline to week 12, assessed by 24-hour ambulatory blood pressure monitoring. Secondary outcomes include changes in office and ambulatory blood pressure, blood pressure control rates, treatment adjustments, time to blood pressure control, and antihypertensive medication burden assessed using defined daily doses.
Exploratory outcomes include changes in cardiac structure and function, urinary albumin-to-creatinine ratio, and circulating renin and aldosterone levels. Treatment safety will be evaluated throughout the study, with particular attention to hyperkalemia, changes in kidney function, symptomatic hypotension, and other adverse events.
Studietype
Studietype
Inschrijving (Geschat)
Inschrijving
Fase
Fase
- Fase 4
Contacten en locaties
Studiecontact
Studiecontact
- Naam: Jiali Song, Prof.
- Telefoonnummer: 86(010)88398866
- E-mail: songjiali@fuwai.com
Studie Locaties
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Beijing Municipality
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Beijing, Beijing Municipality, China, 100037
- Fuwai Hospital
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Deelname Criteria
Geschiktheidscriteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Age 18 years or older.
- Either untreated hypertension, defined as mean seated office systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or hypertension currently treated with no more than two antihypertensive agents.
- Plasma direct renin concentration <12 mU/L after the protocol-specified medication washout: at least 4 weeks for mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and other diuretics; and at least 2 weeks for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and beta-blockers.
- Willing and able to provide written informed consent.
Exclusion Criteria:
- Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥120 mmHg.
- Current use of mineralocorticoid receptor antagonists or other medications that interfere with renin or aldosterone measurements, including glucocorticoids, oral estrogens, and sodium-glucose cotransporter 2 inhibitors.
- Pregnancy, breastfeeding, or women of childbearing potential who are not using reliable contraception.
- Body mass index ≥37.5 kg/m².
- Serum potassium ≥5.0 mmol/L.
- Diabetes mellitus with glycated hemoglobin ≥7.5%.
- Chronic kidney disease with estimated glomerular filtration rate ≤45 mL/min/1.73 m² or urine dipstick protein >2+.
- New York Heart Association functional class II-IV heart failure, coronary artery disease, or a history of transient ischemic attack, stroke, or atrial fibrillation.
- Hepatic impairment with alanine aminotransferase or aspartate aminotransferase ≥2 times the upper limit of normal.
- Secondary hypertension or another condition affecting blood pressure regulation, including licorice abuse, primary hyperparathyroidism, primary aldosteronism, autonomous cortisol secretion, hyperthyroidism, pheochromocytoma, renal artery stenosis, or known monogenic low-renin hypertension.
- Known allergy or intolerance to any study medication or its components.
- Inability to tolerate the required medication washout period.
- Any other condition that, in the investigator's judgment, makes participation unsuitable.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Enkel
Aantal wapens
Wapens en interventies
Deelnemersgroep / ArmDeelnemersgroep / Arm |
Interventie / BehandelingInterventie / Behandeling |
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Experimenteel: Early Eplerenone-Based Treatment
Participants will receive stepped antihypertensive treatment starting with eplerenone 50 mg orally once daily. Treatment will be intensified as needed by sequentially adding amlodipine 5 mg once daily, increasing eplerenone to 50 mg twice daily, increasing amlodipine to 5 mg twice daily, adding hydrochlorothiazide 12.5 mg once daily, adding doxazosin 4 mg once daily, and increasing hydrochlorothiazide to 25 mg once daily. Participants taking two antihypertensive drugs before washout will generally start with eplerenone plus amlodipine. Treatment adjustments will depend on blood pressure, tolerability, and safety assessments, with a target seated office blood pressure below 140/90 mmHg. Treatment will continue for 24 weeks. |
Eplerenone will be administered orally at 50 mg once daily as the initial treatment in the experimental arm. The dose may be increased to 50 mg twice daily according to the prespecified treatment algorithm, blood pressure response, tolerability, serum potassium, and kidney function. Treatment will continue for 24 weeks, with dose reduction or interruption when clinically indicated. |
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Actieve vergelijker: Standard Treatment
Participants will receive stepped antihypertensive treatment starting with telmisartan 40 mg orally once daily. Treatment will be intensified as needed by sequentially adding amlodipine 5 mg once daily, increasing telmisartan to 80 mg once daily, increasing amlodipine to 5 mg twice daily, adding hydrochlorothiazide 12.5 mg once daily, adding doxazosin 4 mg once daily, and increasing hydrochlorothiazide to 25 mg once daily. Participants taking two antihypertensive drugs before washout will generally start with telmisartan plus amlodipine. Treatment adjustments will depend on blood pressure, tolerability, and safety assessments, with a target seated office blood pressure below 140/90 mmHg. Treatment will continue for 24 weeks. |
Telmisartan will be administered orally at 40 mg once daily as the initial treatment in the active comparator arm. The dose may be increased to 80 mg once daily according to the prespecified treatment algorithm, blood pressure response, and tolerability. Treatment will continue for 24 weeks, with dose reduction or interruption when clinically indicated. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Change From Baseline in Mean Daytime Ambulatory Systolic Blood Pressure at Week 12
Tijdsspanne: Baseline and Week 12
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Change in mean daytime systolic blood pressure, measured in mmHg by 24-hour ambulatory blood pressure monitoring, from baseline to Week 12. Mean daytime systolic blood pressure is the average of all valid daytime systolic readings. A valid recording requires at least 70% of scheduled readings, including at least 20 daytime readings and 7 nighttime readings. Change is calculated as the Week 12 value minus the baseline value; a negative value indicates a reduction in blood pressure. |
Baseline and Week 12
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Secundaire uitkomstmaten
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Change From Baseline in Office Systolic Blood Pressure
Tijdsspanne: Baseline, Week 12, and Week 24
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Change in seated office systolic blood pressure, measured in mmHg, from baseline to each assessment. Measurements are obtained after at least 5 minutes of seated rest using a standardized upper-arm blood pressure monitor. |
Baseline, Week 12, and Week 24
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Change From Baseline in Office Diastolic Blood Pressure
Tijdsspanne: Baseline, Week 12, and Week 24
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Change in seated office diastolic blood pressure, measured in mmHg, from baseline to each assessment. Measurements are obtained after at least 5 minutes of seated rest using a standardized upper-arm blood pressure monitor. |
Baseline, Week 12, and Week 24
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Percentage of Participants Achieving Office Blood Pressure Control
Tijdsspanne: Week 12 and Week 24
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Percentage of participants with seated office systolic blood pressure below 140 mmHg and diastolic blood pressure below 90 mmHg at each assessment. |
Week 12 and Week 24
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Percentage of Participants Achieving an Office Blood Pressure Response
Tijdsspanne: Baseline, Week 12, and Week 24
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Percentage of participants with a reduction from baseline in office systolic blood pressure of at least 10 mmHg, a reduction in office diastolic blood pressure of at least 5 mmHg, or achievement of office blood pressure below 140/90 mmHg. |
Baseline, Week 12, and Week 24
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Number of Antihypertensive Treatment Adjustments
Tijdsspanne: From randomization through Week 24
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Cumulative number of antihypertensive treatment adjustments per participant, including dose increases, addition of a drug, and discontinuation of a drug. |
From randomization through Week 24
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Time to First Documented Office Blood Pressure Control
Tijdsspanne: From randomization through Week 24
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Time, measured in weeks from randomization, to the first study visit at which seated office systolic blood pressure is below 140 mmHg and diastolic blood pressure is below 90 mmHg. |
From randomization through Week 24
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Mean 24-Hour Ambulatory Systolic Blood Pressure
Tijdsspanne: Week 12 and Week 24
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Mean systolic blood pressure, measured in mmHg, calculated from all valid readings during 24-hour ambulatory blood pressure monitoring at each assessment. |
Week 12 and Week 24
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Mean 24-Hour Ambulatory Diastolic Blood Pressure
Tijdsspanne: Week 12 and Week 24
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Mean diastolic blood pressure, measured in mmHg, calculated from all valid readings during 24-hour ambulatory blood pressure monitoring at each assessment. |
Week 12 and Week 24
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Mean Nighttime Ambulatory Systolic Blood Pressure
Tijdsspanne: Week 12 and Week 24
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Mean systolic blood pressure, measured in mmHg, calculated from all valid nighttime readings during ambulatory blood pressure monitoring at each assessment. |
Week 12 and Week 24
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Mean Nighttime Ambulatory Diastolic Blood Pressure
Tijdsspanne: Week 12 and Week 24
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Mean diastolic blood pressure, measured in mmHg, calculated from all valid nighttime readings during ambulatory blood pressure monitoring at each assessment. |
Week 12 and Week 24
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Mean Daytime Ambulatory Diastolic Blood Pressure
Tijdsspanne: Week 12 and Week 24
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Mean diastolic blood pressure, measured in mmHg, calculated from all valid daytime readings during ambulatory blood pressure monitoring at each assessment. |
Week 12 and Week 24
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Antihypertensive Medication Burden at Achievement of Target Office Blood Pressure
Tijdsspanne: At achievement of target office blood pressure during the 24-week treatment period
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Total antihypertensive medication burden required to achieve office blood pressure below 140/90 mmHg, expressed in World Health Organization defined daily dose equivalents. For each drug, the prescribed daily dose is divided by its defined daily dose, and the resulting values are summed across drugs. |
At achievement of target office blood pressure during the 24-week treatment period
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Andere uitkomstmaten
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Change From Baseline in Left Ventricular Mass Index
Tijdsspanne: Baseline and Week 24
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Change in echocardiographically measured left ventricular mass indexed to body surface area, expressed in g/m². |
Baseline and Week 24
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Change From Baseline in Left Atrial Volume Index
Tijdsspanne: Baseline and Week 24
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Change in left atrial volume indexed to body surface area, measured by echocardiography and expressed in mL/m² |
Baseline and Week 24
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Change From Baseline in Urinary Albumin-to-Creatinine Ratio
Tijdsspanne: Baseline and Week 24
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Change in urinary albumin-to-creatinine ratio, calculated by dividing urinary albumin concentration by urinary creatinine concentration |
Baseline and Week 24
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Change From Baseline in Plasma Aldosterone Concentration
Tijdsspanne: Baseline and Week 24
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Change in plasma aldosterone concentration, measured using a standardized chemiluminescent immunoassay. |
Baseline and Week 24
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Change From Baseline in Direct Renin Concentration
Tijdsspanne: Baseline and Week 24
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Change in direct renin concentration, expressed in mU/L and measured using the DiaSorin LIAISON chemiluminescent immunoassay |
Baseline and Week 24
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Change From Baseline in Aldosterone-to-Renin Ratio
Tijdsspanne: Baseline and Week 24
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Change in the ratio of plasma aldosterone concentration to direct renin concentration |
Baseline and Week 24
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Medewerkers en onderzoekers
Sponsor
Sponsor
Publicaties en nuttige links
Algemene publicaties
- Kario K, Katsuya T, Shimosawa T, Taguchi T, Tanabe A, Ohishi M; ESCORT-HT investigators. Rationale and Design of a Randomized, Open-Label, Parallel-Group Study of Esaxerenone Versus Angiotensin Receptor Blockers in Older Patients With Uncontrolled Hypertension on Calcium Channel Blocker Monotherapy (ESCORT-HT). J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14947. doi: 10.1111/jch.14947. Epub 2024 Nov 25.
- Shah SS, Gwini SM, Stowasser M, Reid CM, Young MJ, Fuller PJ, Yang J. A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design. J Hum Hypertens. 2024 Sep;38(9):663-668. doi: 10.1038/s41371-024-00931-4. Epub 2024 Jul 18.
- Shah SS, Fuller PJ, Young MJ, Yang J. Update on Low-Renin Hypertension: Current Understanding and Future Direction. Hypertension. 2024 Oct;81(10):2038-2048. doi: 10.1161/HYPERTENSIONAHA.124.23385. Epub 2024 Aug 13.
- Shah SS, Zhang J, Gwini SM, Young MJ, Fuller PJ, Yang J. Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis. J Hum Hypertens. 2024 May;38(5):383-392. doi: 10.1038/s41371-023-00891-1. Epub 2024 Jan 11.
- Weinberger MH, White WB, Ruilope LM, MacDonald TM, Davidson RC, Roniker B, Patrick JL, Krause SL. Effects of eplerenone versus losartan in patients with low-renin hypertension. Am Heart J. 2005 Sep;150(3):426-33. doi: 10.1016/j.ahj.2004.12.005.
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Studie start
Primaire voltooiing (Geschat)
Primaire voltooiing
Studie voltooiing (Geschat)
Studie voltooiing
Studieregistratiedata
Eerst ingediend
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Eerst ingediend dat voldeed aan de QC-criteria
Eerst ingediend dat voldeed aan de QC-criteria
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Updates van studierecords
Laatste update geplaatst (Werkelijk)
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Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Vaatziekten
- Hart-en vaatziekten
- Hypertensie
- Organische chemicaliën
- Heterocyclische verbindingen
- Benzimidazolen
- Heterocyclische verbindingen, 2-ring
- Heterocyclische verbindingen, gefuseerd ring
- Koolwaterstoffen
- Koolwaterstoffen, cyclisch
- Koolwaterstoffen, aromatisch
- Polycyclische verbindingen
- Zwangere
- Steroïden
- Verbindingen met gefuseerde ring
- Benzeenderivaten
- Lactonen
- Zwangeres
- Bifenylverbindingen
- Telmisartan
- Eplerenon
Andere studie-ID-nummers
Andere studie-ID-nummers
- 2026-3206
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
The plan for sharing de-identified individual participant data has not yet been determined. The decision will consider participant consent, ethics committee requirements, institutional policies, and applicable data protection regulations. This statement will be updated once a decision has been made.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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