Browsing by Author "Wheaton, Olivia"

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    Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note
    (MDPI, 2023-09-06) Panigrahy, Ashok; Schmithorst, Vanessa; Ceschin, Rafael; Lee, Vince; Beluk, Nancy; Wallace, Julia; Wheaton, Olivia; Chenevert, Thomas; Qiu, Deqiang; Lee, James N.; Nencka, Andrew; Gagoski, Borjan; Berman, Jeffrey I.; Yuan, Weihong; Macgowan, Christopher; Coatsworth, James; Fleysher, Lazar; Cannistraci, Christopher; Sleeper, Lynn A.; Hoskoppal, Arvind; Silversides, Candice; Radhakrishnan, Rupa; Markham, Larry; Rhodes, John F.; Dugan, Lauryn M.; Brown, Nicole; Ermis, Peter; Fuller, Stephanie; Cotts, Timothy Brett; Rodriguez, Fred Henry; Lindsay, Ian; Beers, Sue; Aizenstein, Howard; Bellinger, David C.; Newburger, Jane W.; Glass Umfleet, Laura; Cohen, Scott; Zaidi, Ali; Gurvitz, Michelle; Pediatric Heart Network MINDS Neuroimaging Ancillary Study Investigators; Radiology and Imaging Sciences, School of Medicine
    Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)”. Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural–physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.
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    A Multi-National Trial of a Direct Oral Anticoagulant in Children with Cardiac Disease: Design and Rationale of the SAXOPHONE Study
    (Elsevier, 2019-11) Payne, R. Mark; Burns, Kristin M.; Glatz, Andrew C.; Li, Danshi; Li, Xiaodong; Monagle, Paul; Newburger, Jane W.; Swan, Elizabeth A.; Wheaton, Olivia; Male, Christoph; Pediatrics, School of Medicine
    Anticoagulation in children is problematic for multiple reasons. Currently used anticoagulants have significant disadvantages and may negatively affect quality of life (QOL). This manuscript describes the design, rationale, and methods of a prospective, randomized, open label phase II multi-national clinical trial of a direct oral anticoagulant (DOAC), apixaban, in children and infants with congenital and acquired heart disease. This trial is designed to gather preliminary safety and pharmacokinetics (PK) data, as well as generate data on QOL of individuals taking apixaban compared to the standard of care (SOC) anticoagulants vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). A key issue this trial seeks to address is the practice of using therapeutics tested in adult trials in the pediatric population without robust pediatric safety or efficacy data. Pediatric heart diseases are not common, and specific diagnoses often meet the criteria of a rare disease; thus, statistical efficacy may be difficult to achieve. This trial will provide valuable PK and safety data intended to inform clinical practice for anticoagulation in pediatric heart diseases, a setting in which a fully powered phase III clinical trial is not feasible. A second consideration this trial addresses is that metrics besides efficacy, such as QOL, have not been traditionally used as endpoints in regulated anticoagulation studies yet may add substantial weight to the clinical decision for use of a DOAC in place of VKA or LMWH. This study examines QOL related to both heart disease and anticoagulation among children randomized to either SOC or apixaban. There are considerable strengths and benefits to conducting a clinical trial in pediatric rare disease populations via an industry-academic collaboration. The SAXOPHONE study represents a collaboration between Bristol-Myers Squibb (BMS)/Pfizer Alliance, and the National Heart, Lung, and Blood Institute's (NHLBI) Pediatric Heart Network (PHN) and may be an attractive model for future pediatric drug trials.