Spironolactone to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): Study protocol for a randomized controlled pilot trial

Trials

Volumn 15, Issue 1, 2014, Pages

  Ng, Khai P ^a   Jain, Poorva ^b   Heer, Gurdip ^b   Redman, Val ^b   Chagoury, Odette L ^b   Dowswell, George ^b   Greenfield, Sheila ^b   Freemantle, Nick ^c   Townend, Jonathan N ^a   Gill, Paramjit S ^b   McManus, Richard J ^d   Ferro, Charles J ^a  

^a QUEEN ELIZABETH HOSPITAL   (United Kingdom)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^c ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

arterial stiffness; cardiovascular events; chronic kidney disease; feasibility; mineralocorticoid receptor antagonist; pulse wave velocity; qualitative; randomized controlled trial; renal dysfunction; spironolactone

Indexed keywords

ALANINE AMINOTRANSFERASE; BILIRUBIN; CREATININE; PLACEBO; POTASSIUM; SPIRONOLACTONE; BIOLOGICAL MARKER; MINERALOCORTICOID ANTAGONIST;

ABDOMINAL DISCOMFORT; AGRANULOCYTOSIS; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AMENORRHEA; ANAPHYLAXIS; ARTERIAL STIFFNESS; ARTICLE; ATAXIA; BILIRUBIN BLOOD LEVEL; BLOOD PRESSURE; BLOOD PRESSURE MEASUREMENT; BRACHIAL ARTERY; BREAST TENDERNESS; BREAST TUMOR; CARDIOVASCULAR DISEASE; CAROTID ARTERY PULSE; CENTRIFUGATION; CHRONIC KIDNEY DISEASE; CLINICAL PROTOCOL; CLINICAL RESEARCH; CONFUSION; CONTACT DERMATITIS; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIARRHEA; DOUBLE BLIND PROCEDURE; DROWSINESS; DRUG EFFECT; DRUG MONITORING; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DUODENUM BLEEDING; DUODENUM ULCER; EOSINOPHILIA; FEASIBILITY STUDY; FEMALE; FEMORAL ARTERY; FOLLOW UP; GENERAL PRACTICE; GLOMERULUS FILTRATION RATE; GYNECOMASTIA; HEADACHE; HIRSUTISM; HUMAN; HYPERKALEMIA; HYPONATREMIA; HYPOTENSION; IMPOTENCE; INTENTION TO TREAT ANALYSIS; KIDNEY DYSFUNCTION; KIDNEY FUNCTION; LETHARGY; LEUKEMIA; LIBIDO DISORDER; LICHEN PLANUS; LIVER CELL CARCINOMA; LIVER TOXICITY; LOW DRUG DOSE; LUPUS LIKE SYNDROME; MAJOR CLINICAL STUDY; MALE; MEDICAL HISTORY; MENORRHAGIA; MICROALBUMINURIA; MODERATE RENAL IMPAIRMENT; MULTICENTER STUDY; NON INVASIVE BLOOD PRESSURE MONITOR; OLIGOMENORRHEA; PATIENT ATTITUDE; PATIENT SAFETY; PHARMACY; PHYSICIAN ATTITUDE; PILOT STUDY; POTASSIUM BLOOD LEVEL; POTASSIUM RESTRICTION; PRIMARY MEDICAL CARE; PROSPECTIVE STUDY; PULSE WAVE; QUALITATIVE RESEARCH; QUALITY CONTROL; QUALITY OF LIFE; QUESTIONNAIRE; RANDOMIZATION; RANDOMIZED CONTROLLED TRIAL; RASH; RISK ASSESSMENT; SIDE EFFECT; STOMACH HEMORRHAGE; STOMACH ULCER; TESTIS TUMOR; THYROID ADENOMA; TREATMENT DURATION; UNITED KINGDOM; VOMITING; ATTITUDE TO HEALTH; BLOOD; CARDIOVASCULAR DISEASES; CHEMICALLY INDUCED; CLINICAL TRIAL; COMPLICATION; DRUG EFFECTS; EARLY DIAGNOSIS; GENERAL PRACTITIONER; HEALTH PERSONNEL ATTITUDE; KIDNEY FAILURE, CHRONIC; METHODOLOGY; PATHOPHYSIOLOGY; PREDICTIVE VALUE; PRIMARY HEALTH CARE; PSYCHOLOGY; TIME; TREATMENT OUTCOME;

ATTITUDE OF HEALTH PERSONNEL; BIOLOGICAL MARKERS; CARDIOVASCULAR DISEASES; CLINICAL PROTOCOLS; DOUBLE-BLIND METHOD; EARLY DIAGNOSIS; ENGLAND; GENERAL PRACTITIONERS; HEALTH KNOWLEDGE, ATTITUDES, PRACTICE; HUMANS; HYPERKALEMIA; KIDNEY FAILURE, CHRONIC; MINERALOCORTICOID RECEPTOR ANTAGONISTS; PILOT PROJECTS; POTASSIUM; PREDICTIVE VALUE OF TESTS; PRIMARY HEALTH CARE; PROSPECTIVE STUDIES; PULSE WAVE ANALYSIS; QUALITATIVE RESEARCH; QUESTIONNAIRES; RESEARCH DESIGN; SPIRONOLACTONE; TIME FACTORS; TREATMENT OUTCOME; VASCULAR STIFFNESS;

EID: 84900435185     PISSN: None     EISSN: 17456215     Source Type: Journal    
DOI: 10.1186/1745-6215-15-158     Document Type: Article

References (57)

1. Black C, Sharma P, Scotland G, McCullough K, McGurn D, Robertson L, Fluck N, MacLeod A, McNamee P, Prescott G, Smith C. Early referral strategies for management of people with markers of renal disease: a systematic review of the evidence of clinical effectiveness, cost-effectiveness and economic analysis. Health Technol Assess 2010, 14(21):1-184.
2. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006, 145(4):247-254. 10.7326/0003-4819-145-4-200608150-00004, 16908915.
3. National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kid Dis 2002, 39(Suppl 1):S1-S266. National Kidney Foundation.
4. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010, 375(9731):2073-2081. 3993088, 20483451.
5. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third national health and nutrition examination survey. Am J Kidney Dis 2003, 41(1):1-12. 10.1053/ajkd.2003.50007, 12500213.
6. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351(13):1296-1305. 10.1056/NEJMoa041031, 15385656.
7. Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 2006, 17(7):2034-2047. 10.1681/ASN.2005101085, 16738019.
8. Mafham M, Emberson J, Landray MJ, Wen CP, Baigent C. Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis. PLoS One 2011, 6(10):e25920. 10.1371/journal.pone.0025920, 3198450, 22039429.
9. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA 2007, 298(17):2038-2047. 10.1001/jama.298.17.2038, 17986697.
10. Murphree DD, Thelen SM. Chronic kidney disease in primary care. J Am Board Fam Med 2010, 23(4):542-550. 10.3122/jabfm.2010.04.090129, 20616297.
11. Richards N, Harris K, Whitfield M, O'Donoghue D, Lewis R, Mansell M, Thomas S, Townend J, Eames M, Marcelli D. Primary care-based disease management of chronic kidney disease (CKD), based on estimated glomerular filtration rate (eGFR) reporting, improves patient outcomes. Nephrol Dial Transplant 2008, 23(2):549-555.
12. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension 2003, 42(5):1050-1065. 10.1161/01.HYP.0000102971.85504.7c, 14604997.
13. Kerr M, Bray B, Medcalf J, O'Donoghue DJ, Matthews B. Estimating the financial cost of chronic kidney disease to the NHS in England. Nephrol Dial Transplant 2012, 27(Suppl 3):iii73-iii80. 3484716, 22815543.
14. Moody WE, Edwards NC, Madhani M, Chue CD, Steeds RP, Ferro CJ, Townend JN. Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: cause or association?. Atherosclerosis 2012, 223(1):86-94. 10.1016/j.atherosclerosis.2012.01.043, 22349087.
15. Chue CD, Townend JN, Steeds RP, Ferro CJ. Arterial stiffness in chronic kidney disease: causes and consequences. Heart 2010, 96(11):817-823. 10.1136/hrt.2009.184879, 20406771.
16. US Renal Data System USRDS 2011 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States 2011, Bethesda, MA: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, US Renal Data System.
17. Edwards NC, Steeds RP, Ferro CJ, Townend JN. The treatment of coronary artery disease in patients with chronic kidney disease. QJM 2006, 99(11):723-736. 10.1093/qjmed/hcl101, 17040978.
18. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 2003, 107(22):2864-2869. 10.1161/01.CIR.0000069826.36125.B4, 12796414.
19. Mourad JJ, Pannier B, Blacher J, Rudnichi A, Benetos A, London GM, Safar ME. Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension. Kidney Int 2001, 59(5):1834-1841. 10.1046/j.1523-1755.2001.0590051834.x, 11318954.
20. McMahon LP, Roger SD, Levin A. Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease. J Am Soc Nephrol 2004, 15(6):1640-1647. 10.1097/01.ASN.0000130566.69170.5E, 15153576.
21. Edwards NC, Ferro CJ, Townend JN, Steeds RP. Aortic distensibility and arterial-ventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction. Heart 2008, 94(8):1038-1043. 10.1136/hrt.2007.137539, 18308865.
22. Coca SG, Krumholz HM, Garg AX, Parikh CR. Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease. JAMA 2006, 296(11):1377-1384. 10.1001/jama.296.11.1377, 16985230.
23. Ng KP, Townend JN, Ferro CJ. Randomised-controlled trials in chronic kidney disease - a call to arms!. Int J Clin Pract 2012, 66(10):913-915.
24. Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RG, Eckardt KU, Kasiske BL, McCullough PA, Passman RS, DeLoach SS, Pun PH, Ritz E. Cardiovascular disease in chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011, 80(6):572-586. 10.1038/ki.2011.223, 21750584.
25. Strippoli GF, Craig JC, Schena FP. The number, quality, and coverage of randomized controlled trials in nephrology. J Am Soc Nephrol 2004, 15(2):411-419. 10.1097/01.ASN.0000100125.21491.46, 14747388.
26. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000, 342(25):1887-1892. 10.1056/NEJM200006223422507, 1557642, 10861325.
27. Goldsmith D. Negative outcome studies in end-stage renal disease. Blood Purif 2008, 26(1):63-66. 10.1159/000110567, 18182799.
28. Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract 2004, 10(2):307-312. 10.1111/j.2002.384.doc.x, 15189396.
29. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C, de Jong PE, de Zeeuw D, Shahinfar S, Ruggenenti P, Remuzzi G, Levey AS. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int 2001, 60(3):1131-1140. 10.1046/j.1523-1755.2001.0600031131.x, 11532109.
30. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004, 351(19):1952-1961. 10.1056/NEJMoa042274, 15516696.
31. Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 2008, 148(1):30-48. 10.7326/0003-4819-148-1-200801010-00190, 17984482.
32. Tonelli M, Isles C, Curhan GC, Tonkin A, Pfeffer MA, Shepherd J, Sacks FM, Furberg C, Cobbe SM, Simes J, Craven T, West M. Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation 2004, 110(12):1557-1563. 10.1161/01.CIR.0000143892.84582.60, 15364796.
33. Di Zhang A, Nguyen Dinh Cat A, Soukaseum C, Escoubet B, Cherfa A, Messaoudi S, Delcayre C, Samuel JL, Jaisser F. Cross-talk between mineralocorticoid and angiotensin II signaling for cardiac remodeling. Hypertension 2008, 52(6):1060-1067. 10.1161/HYPERTENSIONAHA.108.117531, 18981328.
34. Iglarz M, Touyz RM, Viel EC, Amiri F, Schiffrin EL. Involvement of oxidative stress in the profibrotic action of aldosterone: interaction with the renin-angiotensin system. Am J Hypertens 2004, 17(7):597-603.
35. Delcayre C, Swynghedauw B. Molecular mechanisms of myocardial remodeling: the role of aldosterone. J Mol Cell Cardiol 2002, 34(12):1577-1584. 10.1006/jmcc.2002.2088, 12505056.
36. Young MJ. Mechanisms of mineralocorticoid receptor-mediated cardiac fibrosis and vascular inflammation. Curr Opin Nephrol Hypertens 2008, 17(2):174-180. 10.1097/MNH.0b013e3282f56854, 18277151.
37. Shavit L, Lifschitz MD, Epstein M. Aldosterone blockade and the mineralocorticoid receptor in the management of chronic kidney disease: current concepts and emerging treatment paradigms. Kidney Int 2012, 81(10):955-968. 10.1038/ki.2011.505, 22336987.
38. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999, 99(18):2434-2439. 10.1161/01.CIR.99.18.2434, 10318666.
39. Ilyas B, Dhaun N, Markie D, Stansell P, Goddard J, Newby DE, Webb DJ. Renal function is associated with arterial stiffness and predicts outcome in patients with coronary artery disease. QJM 2009, 102(3):183-191.
40. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, . the Randomized Aldactone Evaluation Study investigators The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999, 341(10):709-717. 10.1056/NEJM199909023411001, 10471456, the Randomized Aldactone Evaluation Study investigators.
41. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348(14):1309-1321. 10.1056/NEJMoa030207, 12668699.
42. Ezekowitz JA, McAlister FA. Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials. Eur Heart J 2009, 30(4):469-477.
43. Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis 2008, 51(2):199-211. 10.1053/j.ajkd.2007.10.040, 18215698.
44. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009, 4(3):542-551. 10.2215/CJN.04750908, 2653663, 19261819.
45. Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol 2009, 54(6):505-512. 10.1016/j.jacc.2009.03.066, 19643310.
46. Edwards NC, Ferro CJ, Kirkwood H, Chue CD, Young AA, Stewart PM, Steeds RP, Townend JN. Effect of spironolactone on left ventricular systolic and diastolic function in patients with early stage chronic kidney disease. Am J Cardiol 2010, 106(10):1505-1511. 10.1016/j.amjcard.2010.07.018, 21059444.
47. Edwards NC, Steeds RP, Chue CD, Stewart PM, Ferro CJ, Townend JN. The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease. Br J Clin Pharmacol 2012, 73(3):447-454. 10.1111/j.1365-2125.2011.04102.x, 3370349, 21950312.
48. Fraser SD, Roderick PJ, McIntyre NJ, Harris S, McIntyre CW, Fluck RJ, Taal MW. Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care. BMC Fam Pract 2013, 14:88. 10.1186/1471-2296-14-88, 3701497, 23800117.
49. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, . the Modification of Diet in Renal Disease study group A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999, 130(6):461-470. 10.7326/0003-4819-130-6-199903160-00002, 10075613, the Modification of Diet in Renal Disease study group.
50. Hickson SS, Butlin M, Broad J, Avolio AP, Wilkinson IB, McEniery CM. Validity and repeatability of the Vicorder apparatus: a comparison with the SphygmoCor device. Hypertens Res 2009, 32(12):1079-1085. 10.1038/hr.2009.154, 19779487.
51. Wright JM, Mattu GS, Perry TL, Gelferc ME, Strange KD, Zorn A, Chen Y. Validation of a new algorithm for the BPM-100 electronic oscillometric office blood pressure monitor. Blood Press Monit 2001, 6(3):161-165. 10.1097/00126097-200106000-00008, 11518840.
52. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001, 33(5):337-343. 10.3109/07853890109002087, 11491192.
53. National Institute for Health and Care Excellence Hypertension: Clinical Management for Primary Hypertension in Adults 2011, London: CG127, National Institute for Health and Care Excellence.
54. University of Birmingham Primary Care Clinical Research and Trials Unit (PC-CRTU). [http://www.birmingham.ac.uk/research/activity/mds/trials/pccrtu/index.aspx], University of Birmingham.
55. Glaser B, Strauss A. The Discovery of Grounded Theory: Strategies for Qualitative Research 1967, Chicago: Aldine.
56. Charmaz KC. Constructing Grounded Theory: A Practical Guide through Qualitative Analysis 2006, London: Sage.
57. QSR International Pty Ltd NVivo qualitative data analysis software; Version 10. [http://www.qsrinternational.com/products_nvivo.aspx?utm_source=NVivo+10+for+Mac], QSR International Pty Ltd.