{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:04:53Z","timestamp":1790888693065,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Enrolment of subjects to clinical trials investigating novel drugs for infectious diseases is an ongoing challenge. In this study, we evaluate factors associated with non-enrolment in treatment trials for invasive candidiasis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective review of pre-screening logs of patients that were assessed for enrolment in the three clinical trials ACTIVE (NCT00413218), APX001-201 (NCT03604705) and ReSTORE (NCT03667690), investigating novel drugs for invasive candidiasis between September 2007 and August 2021 to identify reasons for study ineligibility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two hundred and fifty-six patients with invasive candidiasis were identified for potential study participation with n\u200a=\u200a154 for the ACTIVE trial, n\u200a=\u200a89 for APX001-201 and n\u200a=\u200a13 for ReSTORE. Half of the potential participants were unable or unwilling to consent. We further identified comorbid conditions such as hepatic or renal impairment [21 hepatic and renal cases (13.6%) in ACTIVE; 12 hepatic (13.5%) and 28 renal cases (31.5%) in APX], prior antifungal treatment [11 cases (7.1%) in ACTIVE; 16 (18.0%) in APX; 7 (38.5%) in ReSTORE] and the last positive culture obtained \u226596\u2005h prior to dosing [1 case (0.6%) in ACTIVE; 7 (7.9%) in APX; 5 (38.5%) in ReSTORE] as relevant reasons for non-enrolment. We also identified criteria repetitively used in the analysed studies that did not contribute substantially to ineligibility rates. Ultimately, 254\/256 patients (99.2%) were ineligible for enrolment in the respective trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study identified barriers to enrolment in clinical trials assessing novel antifungal agents in invasive candidiasis. Identification of eligibility criteria associated with non-enrolment allows modification of future trial designs and may ultimately result in higher recruitment rates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac344","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T08:08:56Z","timestamp":1665389336000},"page":"3475-3481","source":"Crossref","is-referenced-by-count":5,"title":["Reason and reality\u2014identifying barriers to patient enrolment for clinical trials in invasive candidiasis"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2457-6437","authenticated-orcid":false,"given":"Rosanne","family":"Sprute","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology (ECMM) , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , Cologne, NRW , Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne , Cologne, NRW , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-231X","authenticated-orcid":false,"given":"Jan H","family":"Grothe","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology (ECMM) , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , Cologne, NRW , Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne , Cologne, NRW , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7680-0344","authenticated-orcid":false,"given":"Sarah","family":"Heringer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology (ECMM) , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , Cologne, NRW , Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne , Cologne, NRW , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-3137","authenticated-orcid":false,"given":"Oliver A","family":"Cornely","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology (ECMM) , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , Cologne, NRW , Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS K\u00f6ln) , Cologne, NRW , Germany"},{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC) , Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"2022112816504910600_dkac344-B1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s10096-014-2230-8","article-title":"Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole","volume":"34","author":"Heimann","year":"2015","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2022112816504910600_dkac344-B2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1086\/421946","article-title":"Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study","volume":"39","author":"Wisplinghoff","year":"2004","journal-title":"Clin Infect 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