{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:26:23Z","timestamp":1770506783876,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,4,7]],"date-time":"2006-04-07T00:00:00Z","timestamp":1144368000000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transplant Infectious Dis"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:p><jats:bold>Abstract: Background. <\/jats:bold> Sensitivity analyses were incorporated in a Phase III study of caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for febrile neutropenic patients to determine the impact of varying definitions of fever resolution on response rates.<\/jats:p><jats:p><jats:bold>Methods. <\/jats:bold> The primary analysis used a 5\u2010part composite endpoint: resolution of any baseline invasive fungal infection, no breakthrough invasive fungal infection, survival, no premature discontinuation of study drug, and fever resolution for 48\u2003h during the period of neutropenia. Pre\u2010specified analyses used 3 other definitions for fever resolution: afebrile for 24\u2003h during the period of neutropenia, afebrile at 7 days post therapy, and eliminating fever resolution altogether from the composite endpoint. Patients were stratified on entry by use of antifungal prophylaxis and risk of infection. Allogeneic hematopoietic stem cell transplants or relapsed acute leukemia defined high\u2010risk patients.<\/jats:p><jats:p><jats:bold>Results. <\/jats:bold> In the primary analysis, 41% of patients in each treatment group met the fever\u2010resolution criteria. Low\u2010risk patients had shorter durations of neutropenia but failed fever\u2010resolution criteria more often than high\u2010risk patients. In each exploratory analysis, response rates increased in both treatment groups compared to the primary analysis, particularly in low\u2010risk patients.<\/jats:p><jats:p><jats:bold>Conclusions. <\/jats:bold> Response rates for the primary composite endpoint for both treatment groups in this study were driven by low rates of fever resolution. Requiring fever resolution during neutropenia in a composite endpoint can mask more clinically relevant outcomes.<\/jats:p>","DOI":"10.1111\/j.1399-3062.2006.00127.x","type":"journal-article","created":{"date-parts":[[2006,4,7]],"date-time":"2006-04-07T08:28:54Z","timestamp":1144398534000},"page":"31-37","source":"Crossref","is-referenced-by-count":28,"title":["Impact of alternate definitions of fever resolution on the composite endpoint in clinical trials of empirical antifungal therapy for neutropenic patients with persistent fever: analysis of results from the Caspofungin Empirical Therapy Study"],"prefix":"10.1111","volume":"8","author":[{"given":"B.E.","family":"De Pauw","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.A.","family":"Sable","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.J.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.J.","family":"Lupinacci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.R.","family":"Bourque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.A.","family":"Wise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.\u2010Y.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.J.","family":"DiNubile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Teppler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,4,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe048203"},{"issue":"1","key":"e_1_2_6_3_2","first-page":"S44","article-title":"The Infectious Diseases Society of America 2002 guidelines for the use of antimicrobial agents in patients with cancer and neutropenia","volume":"39","author":"Rolston KV.","year":"2004","journal-title":"salient features and comments"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-135-6-200109180-00010"},{"key":"e_1_2_6_5_2","first-page":"2554","article-title":"Composite outcomes in randomized trials","volume":"289","author":"Freemantle N","year":"2003","journal-title":"greater precision but with greater uncertainty?"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2003.11.002"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401004"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200201243460403"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040446"},{"key":"e_1_2_6_10_2","first-page":"1746","article-title":"Voriconazole for empirical antifungal therapy","volume":"346","author":"Walsh TJ","year":"2002","journal-title":"N Engl J Med"},{"key":"e_1_2_6_11_2","first-page":"1610","article-title":"Fever and infection in leukemic patients","volume":"41","author":"Bodey GP","year":"1978","journal-title":"a study of 494 consecutive patients"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(84)90283-3"},{"key":"e_1_2_6_13_2","first-page":"3038","article-title":"The Multinational Association for Supportive Care in Cancer risk index","volume":"18","author":"Klastersky J","year":"2000","journal-title":"a multinational scoring system for identifying low-risk febrile neutropenic cancer patients"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-197607000-00008"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198205000-00003"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/322631"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200201243460410"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)00457-X"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00239.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/archinte.1991.00400040107024","article-title":"Amphotericin B vs high\u2010dose ketoconazole for empirical antifungal therapy among febrile, granulocytopenic cancer patients. 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