Treatment for first cytomegalovirus infection post–hematopoietic cell transplant in the AURORA trial: A multicenter, double-blind, randomized, phase 3 trial comparing maribavir with valganciclovir Journal Article
| Authors: | Papanicolaou, G. A.; Avery, R. K.; Cordonnier, C.; Duarte, R. F.; Haider, S.; Maertens, J.; Peggs, K. S.; Solano, C.; Young, J. A. H.; Fournier, M.; Murray, R. A.; Wu, J.; Winston, D. J.; for the AURORA Trial Investigators |
| Article Title: | Treatment for first cytomegalovirus infection post–hematopoietic cell transplant in the AURORA trial: A multicenter, double-blind, randomized, phase 3 trial comparing maribavir with valganciclovir |
| Abstract: | Background. Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir. Methods. In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed. Results. Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference: −7.7%; 95% confidence interval [CI]: −14.98, −.36; lower limit of 95% CI of treatment difference exceeded −7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference: 4.4%; 95% CI: −3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%). Conclusions. Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration. NCT02927067 [AURORA]. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. |
| Keywords: | adult; controlled study; aged; middle aged; young adult; major clinical study; clinical trial; constipation; fatigue; neutropenia; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; follow up; neutrophil count; anemia; leukopenia; nausea; randomized controlled trial; thrombocytopenia; vomiting; creatinine; creatinine blood level; kidney failure; hematopoietic stem cell transplantation; abdominal pain; asthenia; coughing; dyspnea; fever; pruritus; hypokalemia; acute graft versus host disease; multicenter study; peripheral edema; taste disorder; recurrent disease; antivirus agent; headache; phase 3 clinical trial; leukocyte count; double blind procedure; tremor; ganciclovir; cytomegalovirus infection; cytomegalovirus; dysgeusia; antiviral therapy; antiviral agents; valganciclovir; post hoc analysis; decreased appetite; comparative effectiveness; viremia; exploratory research; benzimidavir; viral clearance; preemptive therapy; cytomegalovirus infections; hematopoietic cell transplant; humans; human; male; female; article; dichlororibofuranosylbenzimidazole; 5,6 dichlorobenzimidazole riboside; maribavir |
| Journal Title: | Clinical Infectious Diseases |
| Volume: | 78 |
| Issue: | 3 |
| ISSN: | 1058-4838 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-03-15 |
| Start Page: | 562 |
| End Page: | 572 |
| Language: | English |
| DOI: | 10.1093/cid/ciad709 |
| PUBMED: | 38036487 |
| PROVIDER: | scopus |
| PMCID: | PMC10954327 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
