Reduction of Left Ventricular Hypertrophy After Eplerenone Therapy

NCT03186742 | Completed Phase 4

• 1 other identifier: 565/14
• Study Type: interventional
• Target: 125
• Locations: 0 countries
• Sites: N/A

Brief Summary

Obstructive sleep apnea syndrome (OSA) is the most frequent sleep disorder characterized by excessive decrease in muscle tone of the soft palate, the tongue and the posterior pharyngeal wall. It leads to airway collapse. In cases of decreased airway passage hypoventilation (hypopnea) occurs while periodic lack of airflow is called apnea. An obstructive sleep apnea syndrome is recognized as an independent cardiovascular risk factor. OSA is very common in patients with resistant hypertension. RAH is diagnosed when blood pressure remains elevated despite simultaneous use of 3 antihypertensive agents from different groups of drugs at optimal to maximum doses, including a diuretic. In patients with OSA frequent episodes of hypoxemia during sleep result in the repeated activation of the sympathetic nervous system. What is more, the episodes of respiratory disorders increases in levels of aldosterone serum concentration with following sodium and water retention and elevation of blood pressure finally. An increased aldosterone level also stimulates synthesis of collagen, promotes stiffening of the arterial wall, myocardial fibrosis with heart muscle remodeling and takes part in development of left ventricular hypertrophy (LVH) - common complication of hypertensive patients with OSA. Several studies, including the Sleep Heart Health Study have confirmed that severe OSA is associated with high prevalence of concentric hypertrophy through sympathetic activation and vasoconstriction. Eplerenone is a selective mineralocorticoid receptor inhibitor. It has no affinity for glucocorticoid, progesterone and androgen receptors and therefore has lower risk of side effects. Eplerenone lowers blood pressure and inhibits heart muscle fibrosis. The hypotensive effect is caused by reduction of fluid retention. Probably, in patients with OSA, a reduction of fluid accumulation especially at the level of the neck may contribute to lowering the resistance in the upper respiratory tract and in that way it may help to decrease the severity of OSA. As LVH remains a strong and independent predictor of total mortality and death from cardiovascular causes, in this study we want to assess whether the addition of Eplerenone to a standard antihypertensive therapy will favorably change left ventricular geometry. We also want to check if the addition the Eplerenone to a standard antihypertensive therapy could be an effective therapeutic option for patients with OSA and RAH.

Conditions

Hypertension,Essential; Obstructive Sleep Apnea; Left Ventricular Hypertrophy

Keywords

Eplerenone; Concentric hypertrophy

Outcome Measures

Primary Outcomes (1)

• Number of patients with reduction of left ventricular hypertrophy after Eplerenone therapy

  Changes in echocardiographic data ( LVED, IVS, LVPW, LVMI, RWT) and in left ventricular geometric patterns after six months Eplerenone treatment

  6 months

Secondary Outcomes (2)

• Reduction in blood pressure after Eplerenone therapy

  6 months

• Reduction in (AHI) apnea-hypopnea index after Eplerenone therapy

  6 months

Study Arms (2)

Group A

EXPERIMENTAL

The patients who had Eplerenone 50mg tab once a day added to their standard hypertensive treatment.

Drug: Eplerenone 50 mg Tab

Group B

NO INTERVENTION

The patients who did not receive an additional drug to their standard hypertensive treatment.

Interventions

Eplerenone 50 mg Tab DRUG

Eplerenone 50 mg Tab once a day

Group A

Eligibility Criteria

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

You may qualify if:

• confirmation of resistant hypertension(RAH). RAH was recognized when in spite of the use of at least 3 antihypertensive agents (including a diuretic) in maximum doses, it was impossible to achieve the target values of BP (\< 140/90 mmHg).
• diagnosing of moderate or severe sleep apnea (OSA) on the basis of apnoea-hypopnea index (AHI) in polysomnography. AHI was defined by the total number of apnoea's and hypopneas per hour of sleep. The severity of OSA was determined as: mild (AHI 5-15), moderate (AHI 15 - 30) and severe (AHI ≥ 30)
• signing informed and written consent to participation in the study.

You may not qualify if:

• secondary hypertension (other than primary hyperaldosteronism),
• myocardial infarction,
• stroke within 6 months before the study,
• congestive heart failure with New York Heart Association (NYHA) grade III-IV,
• chronic kidney disease (GFR \< 30 ml/min),
• active addiction to alcohol or psychoactive substances,
• active cancer disease.

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Related Publications (18)

• Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999 Aug 1;22(5):667-89. No abstract available.

  PMID: 10450601 RESULT

• Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ. 2000 Feb 19;320(7233):479-82. doi: 10.1136/bmj.320.7233.479.

  PMID: 10678860 RESULT

• Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, O'Connor GT, Boland LL, Schwartz JE, Samet JM. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001 Jan;163(1):19-25. doi: 10.1164/ajrccm.163.1.2001008.

  PMID: 11208620 RESULT

• ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013 Oct;31(10):1925-38. doi: 10.1097/HJH.0b013e328364ca4c. No abstract available.

  PMID: 24107724 RESULT

• Drager LF, Bortolotto LA, Figueiredo AC, Silva BC, Krieger EM, Lorenzi-Filho G. Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling. Chest. 2007 May;131(5):1379-86. doi: 10.1378/chest.06-2703.

  PMID: 17494787 RESULT

• Cioffi G, Russo TE, Stefenelli C, Selmi A, Furlanello F, Cramariuc D, Gerdts E, de Simone G. Severe obstructive sleep apnea elicits concentric left ventricular geometry. J Hypertens. 2010 May;28(5):1074-82. doi: 10.1097/hjh.0b013e328336c90a.

  PMID: 20411620 RESULT

• Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, Gottlieb DJ. Left ventricular morphology and systolic function in sleep-disordered breathing: the Sleep Heart Health Study. Circulation. 2008 May 20;117(20):2599-607. doi: 10.1161/CIRCULATIONAHA.107.717892. Epub 2008 May 5.

  PMID: 18458174 RESULT

• Alchanatis M, Paradellis G, Pini H, Tourkohoriti G, Jordanoglou J. Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure. Respiration. 2000;67(4):367-71. doi: 10.1159/000029532.

  PMID: 10940788 RESULT

• Yamaguchi T, Takata Y, Usui Y, Asanuma R, Nishihata Y, Kato K, Shiina K, Yamashina A. Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep Apnea. Am J Hypertens. 2016 Mar;29(3):372-8. doi: 10.1093/ajh/hpv115. Epub 2015 Jul 23.

  PMID: 26208670 RESULT

• Gaddam K, Pimenta E, Thomas SJ, Cofield SS, Oparil S, Harding SM, Calhoun DA. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010 Aug;24(8):532-7. doi: 10.1038/jhh.2009.96. Epub 2009 Dec 17.

  PMID: 20016520 RESULT

• Struthers A, Krum H, Williams GH. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol. 2008 Apr;31(4):153-8. doi: 10.1002/clc.20324.

  PMID: 18404673 RESULT

• Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000 Jul 25;102(4):470-9. doi: 10.1161/01.cir.102.4.470. No abstract available.

  PMID: 10908222 RESULT

• Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989 Sep-Oct;2(5):358-67. doi: 10.1016/s0894-7317(89)80014-8.

  PMID: 2698218 RESULT

• Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986 Feb 15;57(6):450-8. doi: 10.1016/0002-9149(86)90771-x.

  PMID: 2936235 RESULT

• Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63. doi: 10.1016/j.echo.2005.10.005. No abstract available.

  PMID: 16376782 RESULT

• Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.

  PMID: 1798888 RESULT

• Smith SS, Oei TP, Douglas JA, Brown I, Jorgensen G, Andrews J. Confirmatory factor analysis of the Epworth Sleepiness Scale (ESS) in patients with obstructive sleep apnoea. Sleep Med. 2008 Oct;9(7):739-44. doi: 10.1016/j.sleep.2007.08.004. Epub 2007 Oct 24.

  PMID: 17921053 RESULT

• Hori T, Sugita Y, Koga E, Shirakawa S, Inoue K, Uchida S, Kuwahara H, Kousaka M, Kobayashi T, Tsuji Y, Terashima M, Fukuda K, Fukuda N; Sleep Computing Committee of the Japanese Society of Sleep Research Society. Proposed supplements and amendments to 'A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects', the Rechtschaffen & Kales (1968) standard. Psychiatry Clin Neurosci. 2001 Jun;55(3):305-10. doi: 10.1046/j.1440-1819.2001.00810.x. No abstract available.

  PMID: 11422885 RESULT

MeSH Terms

Conditions

Essential Hypertension; Sleep Apnea, Obstructive; Hypertrophy, Left Ventricular

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Andrzej Tykarski, Prof

  Department of Hypertension, Angiology and Internal Disease. Poznan University of Medical Sciences, Poland

  STUDY CHAIR

• Szczepan Cofta, PhD

  Department of Respiratory Diseases, Allergology and Lung Oncology. Poznan University of Medical Sciences, Poland

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 10, 2017
• First Posted: June 14, 2017
• Study Start: July 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 14, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share