Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: Results from a phase 3 randomized clinical trial Journal Article


Authors: Avery, R. K.; Alain, S.; Alexander, B. D.; Blumberg, E. A.; Chemaly, R. F.; Cordonnier, C.; Duarte, R. F.; Florescu, D. F.; Kamar, N.; Kumar, D.; Maertens, J.; Marty, F. M.; Papanicolaou, G. A.; Silveira, F. P.; Witzke, O.; Wu, J.; Sundberg, A. K.; Fournier, M.; for the SOLSTICE Trial Investigators
Article Title: Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: Results from a phase 3 randomized clinical trial
Abstract: Background Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. Methods In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. Results 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80–42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02–16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. Conclusions Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).
Keywords: adult; aged; confidence intervals; randomized controlled trials; descriptive statistics; middle age; treatment outcomes; transplant recipients; antiviral agents -- therapeutic use; comparative studies; random assignment; drug resistance, microbial; pretest-posttest design; human; male; female; cytomegalovirus infections -- drug therapy; antiviral agents -- adverse effects
Journal Title: Clinical Infectious Diseases
Volume: 75
Issue: 4
ISSN: 1058-4838
Publisher: Oxford University Press  
Date Published: 2022-08-15
Start Page: 690
End Page: 701
Language: English
DOI: 10.1093/cid/ciab988
PROVIDER: EBSCOhost
PROVIDER: cinahl
PMCID: PMC9464078
PUBMED: 34864943
DOI/URL:
Notes: Accession Number: 159060022 -- Entry Date: 20220921 -- Revision Date: 20220921 -- Publication Type: Article; pictorial; research; tables/charts; randomized controlled trial -- Journal Subset: Biomedical. -- Source: Cinahl
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