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.

Autor:	Papanicolaou, Genovefa A, Avery, Robin K, Cordonnier, Catherine, Duarte, Rafael F, Haider, Shariq, Maertens, Johan, Peggs, Karl S, Solano, Carlos, Young, Jo-Anne H, Fournier, Martha, Murray, Rose Ann, Wu, Jingyang, Winston, Drew J, Investigators, AURORA Trial
Předmět:	HEMATOPOIETIC stem cell transplantation PROTEIN kinase inhibitors DRUG toxicity PATIENT safety DRUG side effects RESEARCH funding CYTOMEGALOVIRUS diseases STATISTICAL sampling BLIND experiment TERMINATION of treatment RANDOMIZED controlled trials DESCRIPTIVE statistics SURGICAL complications VALGANCICLOVIR DRUG efficacy RESEARCH VIREMIA CONFIDENCE intervals PATIENT aftercare NEUTROPENIA
Zdroj:	Clinical Infectious Diseases; 3/15/2024, Vol. 78 Issue 3, p562-572, 11p
Abstrakt:	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]. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu