{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:37:38Z","timestamp":1785551858775,"version":"3.56.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change \u00b1 standard error: \u2212 0.38 \u00b1 0.08 kg vs. +0.13 \u00b1 0.11 kg; P &amp;lt; 0.001) and at Weeks 1, 2, and 4 (P &amp;lt; 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the lixivaptan group vs. placebo. The TMT-B and MOS-6 showed no significant differences between groups. Lixivaptan was well tolerated\u2014thirst and polyuria occurred more frequently vs. placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In outpatients with HF and volume overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated.<\/jats:p>\n                    <jats:p>Trial registration: NCT01055912<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfs051","type":"journal-article","created":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T00:33:52Z","timestamp":1334709232000},"page":"642-651","source":"Crossref","is-referenced-by-count":19,"title":["The Efficacy and Safety of Lixivaptan in Outpatients with Heart Failure and Volume Overload: Results of a Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study"],"prefix":"10.1093","volume":"14","author":[{"given":"Jalal K.","family":"Ghali","sequence":"first","affiliation":[{"name":"Detroit Medical Center Cardiovascular Institute , Detroit, MI, 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Cardiokine Biopharma, Inc. , Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Abraham","sequence":"additional","affiliation":[{"name":"The Ohio State University , Columbus, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the CK-LX2401 Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,18]]},"reference":[{"key":"2026011921180842700_ejhfhfs051-bib-0001","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cardfail.2009.12.021","article-title":"The critical link of hypervolemia and hyponatremia in heart failure and the potential role of arginine vasopressin antagonists","volume":"16","author":"Ghali","year":"2010","journal-title":"J Card Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0002","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/0002-9149(90)91166-4","article-title":"Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy","volume":"66","author":"Stevenson","year":"1990","journal-title":"Am J Cardiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0003","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1161\/01.CIR.96.4.1165","article-title":"Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in survivors with advanced heart failure","volume":"96","author":"Steimle","year":"1997","journal-title":"Circulation"},{"key":"2026011921180842700_ejhfhfs051-bib-0004","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1067\/mhj.2000.110933","article-title":"Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure","volume":"140","author":"Lucas","year":"2000","journal-title":"Am Heart J"},{"key":"2026011921180842700_ejhfhfs051-bib-0005","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1161\/CIRCHEARTFAILURE.109.923300","article-title":"Chronic ambulatory intracardiac pressures and future heart failure events","volume":"3","author":"Stevenson","year":"2010","journal-title":"Circ Heart Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0006","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/eurjhf\/hfq019","article-title":"Critical elements of clinical follow-up after hospital discharge for heart failure: insights from the EVEREST Trial","volume":"12","author":"Dunlay","year":"2010","journal-title":"Eur J Heart Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0007","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1056\/NEJM199908193410806","article-title":"Hormones and hemodynamics in heart failure","volume":"341","author":"Shrier","year":"1999","journal-title":"N Engl J Med"},{"key":"2026011921180842700_ejhfhfs051-bib-0008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-103-1-1","article-title":"Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis","volume":"103","author":"Francis","year":"1985","journal-title":"Ann Intern Med"},{"key":"2026011921180842700_ejhfhfs051-bib-0009","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/hrt.57.1.17","article-title":"Untreated heart failure: clinical and neuroendocrine effects of introducing diuretics","volume":"57","author":"Bayliss","year":"1987","journal-title":"Br Heart J"},{"key":"2026011921180842700_ejhfhfs051-bib-0010","first-page":"331","article-title":"Relationship between heart failure treatment and development of worsening renal function among hospitalized patients","volume":"147","author":"Butler","year":"2004","journal-title":"Am Heart J"},{"key":"2026011921180842700_ejhfhfs051-bib-0011","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/00000441-200001000-00002","article-title":"Diuretic complications","volume":"319","author":"Greenberg","year":"2000","journal-title":"Am J Med"},{"key":"2026011921180842700_ejhfhfs051-bib-0012","first-page":"1308","article-title":"Furosemide in the long term management of heart failure: the good the bad and the uncertain","volume":"44","author":"Weber","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0013","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.jacc.2004.04.059","article-title":"Furosemide and the progression of left ventricular dysfunction in experimental heart failure","volume":"44","author":"McCurley","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0014","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1161\/01.CIR.100.12.1311","article-title":"Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction","volume":"100","author":"Cooper","year":"1999","journal-title":"Circulation"},{"key":"2026011921180842700_ejhfhfs051-bib-0015","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1093\/eurheartj\/ehi890","article-title":"Heart failure, chronic diuretic use, and increase on mortality and hospitalization: an observational study using propensity score methods","volume":"27","author":"Ahmed","year":"2006","journal-title":"Eur Heart J"},{"key":"2026011921180842700_ejhfhfs051-bib-0016","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.ejheart.2007.07.011","article-title":"Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE Trial","volume":"9","author":"Hasselblad","year":"2007","journal-title":"Eur J Heart Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0017","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.cardfail.2008.01.015","article-title":"The association between high-dose diuretics and clinical stability in ambulatory chronic heart failure patients","volume":"14","author":"Mielniczuk","year":"2008","journal-title":"J Card Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0018","doi-asserted-by":"crossref","first-page":"847","DOI":"10.2165\/00003495-200767060-00002","article-title":"Therapeutic potential of vasopressin receptor antagonists","volume":"67","author":"Ali","year":"2007","journal-title":"Drugs"},{"key":"2026011921180842700_ejhfhfs051-bib-0019","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/eurjhf\/hfq226","article-title":"Short and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO Study","volume":"13","author":"Aronson","year":"2011","journal-title":"Eur J Heart Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0020","doi-asserted-by":"crossref","first-page":"F273","DOI":"10.1152\/ajprenal.00195.2005","article-title":"Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure","volume":"290","author":"Costello-Boerrigter","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0021","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/j.jacc.2007.01.091","article-title":"Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction","volume":"49","author":"Udelson","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0022","doi-asserted-by":"crossref","first-page":"p439","DOI":"10.1007\/978-1-4615-4871-3_55","volume-title":"Vasopressin and Oxytocin. Molecular, Cellular, and Clinical Advances","author":"Chan","year":"1998"},{"key":"2026011921180842700_ejhfhfs051-bib-0023","first-page":"1","article-title":"Effects of single dose administration of lixivaptan, a selective V2 receptor antagonist, or furosemide in healthy volunteers [abstract 1065]","volume":"12","author":"Abraham","year":"2010","journal-title":"Eur J Heart Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0024","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.jacc.2005.11.071","article-title":"Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients","volume":"47","author":"Abraham","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026011921180842700_ejhfhfs051-bib-0025","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1681\/ASN.V10102165","article-title":"Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure","volume":"10","author":"Martin","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"2026011921180842700_ejhfhfs051-bib-0026","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1161\/01.CIR.0000070422.41439.04","article-title":"Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial","volume":"107","author":"Gheorghiade","year":"2003","journal-title":"Circulation"},{"key":"2026011921180842700_ejhfhfs051-bib-0027","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1001\/jama.291.16.1963","article-title":"Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening HF: a randomized controlled trial","volume":"291","author":"Gheorghiade","year":"2004","journal-title":"JAMA"},{"key":"2026011921180842700_ejhfhfs051-bib-0028","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1001\/jama.297.12.1319","article-title":"Effects of oral tolvaptan in patients hospitalized for worsening heart failure. The EVEREST Outcome Trial","volume":"297","author":"Konstam","year":"2007","journal-title":"JAMA"},{"issue":"3","key":"2026011921180842700_ejhfhfs051-bib-0029","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1054\/jcaf.2000.16719","article-title":"The COHERE Registry: hype or hope","volume":"6","author":"Ghali","year":"2000","journal-title":"J Card Fail"},{"key":"2026011921180842700_ejhfhfs051-bib-0030","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1752-8062.2010.00217.x","article-title":"Rationale and design of the treatment of hyponatremia based on lixivaptan in NYHA Class III\/IV cardiac patient evaluation (THE BALANCE) Study","volume":"3","author":"Abraham","year":"2010","journal-title":"Clin Transl Sci"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfs051","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfs051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1093\/eurjhf\/hfs051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1093\/eurjhf\/hfs051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/14\/6\/642\/66442829\/eurjhf_14_6_642.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/14\/6\/642\/66442829\/eurjhf_14_6_642.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:24:08Z","timestamp":1768875848000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/14\/6\/642\/8428974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,1]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,2,18]]},"published-print":{"date-parts":[[2012,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjhf\/hfs051","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,6]]},"published":{"date-parts":[[2012,6,1]]}}}