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A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation.
- Source :
-
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2019 Feb; Vol. 25 (2), pp. 369-381. Date of Electronic Publication: 2018 Oct 04. - Publication Year :
- 2019
-
Abstract
- Cytomegalovirus (CMV) infection is a common complication of allogeneic hematopoietic cell transplantation (HCT). In this trial, we randomized adult CMV-seropositive HCT recipients without CMV viremia at screening 2:1 to receive brincidofovir or placebo until week 14 post-HCT. Randomization was stratified by center and risk of CMV infection. Patients were assessed weekly through week 15 and every third week thereafter through week 24 post-HCT. Patients who developed clinically significant CMV infection (CS-CMVi; CMV viremia requiring preemptive therapy or CMV disease) discontinued the study drug and began anti-CMV treatment. The primary endpoint was the proportion of patients with CS-CMVi through week 24 post-HCT; patients who discontinued the trial or with missing data were imputed as primary endpoint events. Between August 2013 and June 2015, 452 patients were randomized at a median of 15 days after HCT and received study drug. The proportion of patients who developed CS-CMVi or were imputed as having a primary endpoint event through week 24 was similar between brincidofovir-treated patients and placebo recipients (155 of 303 [51.2%] versus 78 of 149 [52.3%]; odds ratio, .95 [95% confidence interval, .64 to 1.41]; P = .805); fewer brincidofovir recipients developed CMV viremia through week 14 compared with placebo recipients (41.6%; P < .001). Serious adverse events were more frequent among brincidofovir recipients (57.1% versus 37.6%), driven by acute graft-versus-host disease (32.3% versus 6.0%) and diarrhea (6.9% versus 2.7%). Week 24 all-cause mortality was 15.5% among brincidofovir recipients and 10.1% among placebo recipients. Brincidofovir did not reduce CS-CMVi by week 24 post-HCT and was associated with gastrointestinal toxicity.<br /> (Copyright © 2018. Published by Elsevier Inc.)
- Subjects :
- Administration, Oral
Adolescent
Adult
Aged
Allografts
Cytomegalovirus Infections etiology
Cytomegalovirus Infections mortality
Cytosine administration & dosage
Cytosine adverse effects
Disease-Free Survival
Female
Humans
Male
Middle Aged
Organophosphonates adverse effects
Survival Rate
Cytomegalovirus
Cytomegalovirus Infections prevention & control
Cytosine analogs & derivatives
Hematopoietic Stem Cell Transplantation
Organophosphonates administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1523-6536
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 30292744
- Full Text :
- https://doi.org/10.1016/j.bbmt.2018.09.038