High-Dose Aldactone for Treatment of Diuretic Resistant Heart Failure

Summary

Prospective, open-label, randomized cohort study comparing adding high-dose spironolactone to usual heart failure care versus usual care in patients with acute decompensated heart failure. Patients will be randomized in a 1:1 fashion to either usual care or high-dose spironolactone plus usual care. Both arms of the study will continue with treatment of ADHF until euvolemia as defined as the resolution of pulmonary edema, peripheral edema, abdominal bloating and/or jugular venous distention. Assessment of clinical status and serum electrolytes, symptoms and renal function will be performed in accordance to standard of care.

Timeline

Start

2014-05

Primary completion

2015-10

Completion

2015-10

Publications

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• Background Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999 Aug 19;341(8):577-85. doi: 10.1056/NEJM199908193410806. No abstract available.
• Background Schrier RW. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med. 2006 Jul;119(7 Suppl 1):S47-53. doi: 10.1016/j.amjmed.2006.05.007.
• Background Schrier RW. Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol. 2007 Jul;18(7):2028-31. doi: 10.1681/ASN.2006111302. Epub 2007 Jun 13.
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• Background Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005 Feb;149(2):209-16. doi: 10.1016/j.ahj.2004.08.005.
• Background Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005 Sep 20;112(12):e154-235. doi: 10.1161/CIRCULATIONAHA.105.167586. Epub 2005 Sep 13. No abstract available.
• Background Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN. The neurohumoral axis in congestive heart failure. Ann Intern Med. 1984 Sep;101(3):370-7. doi: 10.7326/0003-4819-101-3-370.
• Background Bayliss J, Norell M, Canepa-Anson R, Sutton G, Poole-Wilson P. Untreated heart failure: clinical and neuroendocrine effects of introducing diuretics. Br Heart J. 1987 Jan;57(1):17-22. doi: 10.1136/hrt.57.1.17.
• Background He XR, Greenberg SG, Briggs JP, Schnermann J. Effects of furosemide and verapamil on the NaCl dependency of macula densa-mediated renin secretion. Hypertension. 1995 Jul;26(1):137-42. doi: 10.1161/01.hyp.26.1.137.
• Background Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-43. doi: 10.1159/000047397.
• Background Abdallah JG, Schrier RW, Edelstein C, Jennings SD, Wyse B, Ellison DH. Loop diuretic infusion increases thiazide-sensitive Na(+)/Cl(-)-cotransporter abundance: role of aldosterone. J Am Soc Nephrol. 2001 Jul;12(7):1335-1341. doi: 10.1681/ASN.V1271335.
• Background Ellison DH, Velazquez H, Wright FS. Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion. J Clin Invest. 1989 Jan;83(1):113-26. doi: 10.1172/JCI113847.
• Background Bansal S, Lindenfeld J, Schrier RW. Sodium retention in heart failure and cirrhosis: potential role of natriuretic doses of mineralocorticoid antagonist? Circ Heart Fail. 2009 Jul;2(4):370-6. doi: 10.1161/CIRCHEARTFAILURE.108.821199.
• Background Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J; ADHERE Scientific Advisory Committee and Investigators. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail. 2007 Aug;13(6):422-30. doi: 10.1016/j.cardfail.2007.03.011.
• Background Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, O'Connor CM, Rich MW, Stevenson LW, Wang Y, Young JB, Krumholz HM. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J. 2004 Feb;147(2):331-8. doi: 10.1016/j.ahj.2003.08.012.
• Background Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL; ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. doi: 10.1159/000164149. Epub 2008 Oct 17.
• Background Butler J, Chirovsky D, Phatak H, McNeill A, Cody R. Renal function, health outcomes, and resource utilization in acute heart failure: a systematic review. Circ Heart Fail. 2010 Nov;3(6):726-45. doi: 10.1161/CIRCHEARTFAILURE.109.920298. No abstract available.
• Background Forman DE, Butler J, Wang Y, Abraham WT, O'Connor CM, Gottlieb SS, Loh E, Massie BM, Rich MW, Stevenson LW, Young JB, Krumholz HM. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004 Jan 7;43(1):61-7. doi: 10.1016/j.jacc.2003.07.031.
• Background Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
• Background Peacock WF 4th, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS, Wu AH; ADHERE Investigators. Cardiac troponin and outcome in acute heart failure. N Engl J Med. 2008 May 15;358(20):2117-26. doi: 10.1056/NEJMoa0706824.
• Background Klein L, Massie BM, Leimberger JD, O'Connor CM, Pina IL, Adams KF Jr, Califf RM, Gheorghiade M; OPTIME-CHF Investigators. Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF). Circ Heart Fail. 2008 May;1(1):25-33. doi: 10.1161/CIRCHEARTFAILURE.107.746933.
• Background Applefeld MM, Newman KA, Sutton FJ, Reed WP, Roffman DS, Talesnick BS, Grove WR. Outpatient dobutamine and dopamine infusions in the management of chronic heart failure: clinical experience in 21 patients. Am Heart J. 1987 Sep;114(3):589-95. doi: 10.1016/0002-8703(87)90757-5.
• Background Felker GM, Mentz RJ. Diuretics and ultrafiltration in acute decompensated heart failure. J Am Coll Cardiol. 2012 Jun 12;59(24):2145-53. doi: 10.1016/j.jacc.2011.10.910.
• Background Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.
• Background Shchekochikhin D, Lindenfeld J, Schrier R. Increased Spironolactone in Advanced Heart Failure: Effect of Doses Greater than 25 mg/Day on Plasma Potassium Concentration. Cardiorenal Med. 2013 Apr;3(1):1-6. doi: 10.1159/000346447. Epub 2013 Jan 30.
• Background Eng M, Bansal S. Use of natriuretic-doses of spironolactone for treatment of loop diuretic resistant acute decompensated heart failure. Int J Cardiol. 2014 Jan 1;170(3):e68-9. doi: 10.1016/j.ijcard.2013.11.023. Epub 2013 Nov 12. No abstract available.

Drugs

Indications