Browsing by Subject "Multiple Organ Failure"

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    Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2010-07) Richardson, Paul G; Soiffer, Robert J; Antin, Joseph H; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L; Steinbach, Gideon; Murray, Karen F; Vogelsang, Georgia B; Chen, Allen R; Krishnan, Amrita; Kernan, Nancy A; Avigan, David E; Spitzer, Thomas R; Shulman, Howard M; Di Salvo, Donald N; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, LJ; Iacobelli, Massimo; McDonald, George B; Guinan, Eva C
    Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.
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    Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol.
    (Journal of clinical hypertension (Greenwich, Conn.), 2020-10) Cohen, Jordana B; Hanff, Thomas C; Corrales-Medina, Vicente; William, Preethi; Renna, Nicolas; Rosado-Santander, Nelson R; Rodriguez-Mori, Juan E; Spaak, Jonas; Andrade-Villanueva, Jaime; Chang, Tara I; Barbagelata, Alejandro; Alfonso, Carlos E; Bernales-Salas, Eduardo; Coacalla, Johanna; Castro-Callirgos, Carlos Augusto; Tupayachi-Venero, Karen E; Medina, Carola; Valdivia, Renzo; Villavicencio, Mirko; Vasquez, Charles R; Harhay, Michael O; Chittams, Jesse; Sharkoski, Tiffany; Byrd, James Brian; Edmonston, Daniel L; Sweitzer, Nancy; Chirinos, Julio A
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin-converting enzyme 2 (ACE2), which facilitates SARS-CoV-2 host cell entry, may be impacted by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long-term outpatient ACEI or ARB upon hospitalization with COVID-19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.