High-Dose Aldactone for Treatment of Diuretic Resistant Heart Failure

NCT02429388 | Withdrawn Phase 4

• 1 other identifier: HSC20140274H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Keywords

Heart failure; Spironolactone; Diuretics

Outcome Measures

Primary Outcomes (1)

• Efficacy of adjunctive high-dose Spironolactone on weight loss.

  Weight will be tracked from enrollment to 7 days or when patient reaches euvolemia for all patients, whichever occurs first.

  7 days

Secondary Outcomes (3)

• Efficacy of adjunctive high-dose Spironolactone on dyspnea.

  7 days

• Risk of hyperkalemia and renal dysfunction with use of adjunctive high-dose Spironolactone.

  7 days

• Length of hospitalization

  7 days

Study Arms (2)

High dose spironolactone

EXPERIMENTAL

This arm of the study will include addition of high dose spironolactone upto 100mg twice daily in adjunct to usual care of hospitalized acute decompensated heart failure patients with loop diuretics.

Drug: Spironolactone

Usual Care

NO INTERVENTION

This arm of the study will continue the usual care of hospitalized acute decompensated heart failure patients with loop diuretics.

Interventions

Spironolactone DRUG

Administration of spironolactone 25-50mg orally twice daily for two days and subsequently titrated upto 100mg twice daily with daily serum potassium monitoring. Spironolactone will continue until patient is euvolemic and appropriate for discharge. Titration of loop diuretics in this arm will not be escalated.

Also known as: aldactone, potassium-sparing diuretics

High dose spironolactone

Eligibility Criteria

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

You may qualify if:

• years or older patients with congestive heart failure
• Hypervolemic by at least 2 of the following criteria: 1) Peripheral edema; 2) jugular venous distention greater than 7 cm; 3) radiographic pulmonary edema or pleural effusion; 4) enlarged liver or ascites; 5) pulmonary rales, paroxysmal nocturnal dyspnea or orthopnea
• Diuretic resistance as defined by loop diuretic requirements of furosemide greater or equal to 160 mg IV total daily dose or equivalent dose of torsemide or bumetanide. ( 1 mg bumetanide = 10 mg torsemide = 20 mg furosemide)
• Estimated glomerular filtration rate (eGFR) of \> 30ml/min. according to the MDRD Study equation at the time of admission.
• Female patients of child bearing potential must have a negative urine pregnancy test to be eligible.

You may not qualify if:

• Acute coronary syndrome
• Patients with a baseline eGFR \< 30 ml/min according to the MDRD equation.
• Baseline potassium serum concentration 5.3 meq/L
• Requirement for intravenous pressors
• Systemic infection
• Patients with concomitant end-stage liver disease
• Significant valvular disease
• Patients with pulmonary embolism
• Patients with high output heart failure
• Pregnant patients

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University Hospital

San Antonio, Texas, 78229, United States

Location

Related Publications (28)

• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. No abstract available.

  PMID: 22179539 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.

  PMID: 10451464 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.

  PMID: 16843085 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.

  PMID: 17568020 BACKGROUND

• Hirsch AT, Pinto YM, Schunkert H, Dzau VJ. Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure. Am J Cardiol. 1990 Oct 2;66(11):22D-30D; discussion 30D-32D. doi: 10.1016/0002-9149(90)90473-e.

  PMID: 2220602 BACKGROUND

• Schrier RW, De Wardener HE. Tubular reabsorption of sodium ion: influence of factors other than aldosterone and glomerular filtration rate. 2. N Engl J Med. 1971 Dec 2;285(23):1292-303. doi: 10.1056/NEJM197112022852305. No abstract available.

  PMID: 4398836 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.

  PMID: 15846257 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.

  PMID: 16160202 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.

  PMID: 6147109 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.

  PMID: 3541995 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.

  PMID: 7607716 BACKGROUND

• Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-43. doi: 10.1159/000047397.

  PMID: 11805380 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.

  PMID: 11423562 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.

  PMID: 2910903 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.

  PMID: 19808361 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.

  PMID: 17675055 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.

  PMID: 14760333 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.

  PMID: 18931492 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.

  PMID: 21081740 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.

  PMID: 14715185 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.

  PMID: 21366472 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.

  PMID: 18480204 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.

  PMID: 19808267 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.

  PMID: 3630900 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.

  PMID: 22676934 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.

  PMID: 24247300 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.

  PMID: 23801997 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.

  PMID: 24268982 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Spironolactone; Sodium Channel Blockers

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cardiovascular Agents; Therapeutic Uses

Study Officials

• Marvin H Eng, M.D.

  University of Texas Heatlh Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2014
• First Posted: April 29, 2015
• Study Start: May 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: April 20, 2016

Record last verified: 2016-04

Locations

US (1)