Dataset Information

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

ABSTRACT: Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was -246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.

SUBMITTER: Morioka I

PROVIDER: S-EPMC9267258 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

Morioka Ichiro I Kakei Yasumasa Y Omori Takashi T Nozu Kandai K Fujioka Kazumichi K Takahashi Naoto N Yoshikawa Tetsushi T Moriuchi Hiroyuki H Ito Yoshinori Y Oka Akira A

Journal of clinical medicine 20220621 13

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the wh ...[more]

PMID: 35806868

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Project description:BackgroundThe treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time.MethodsWe conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline.ResultsA total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64).ConclusionsTreating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Project description:BackgroundHearing impairment and neurodevelopmental disorders pose a significant global health burden in children. The link between postnatal cytomegalovirus (CMV) infection and these outcomes remains unclear. This study explored the association of postnatal CMV infection with hearing and neurodevelopmental outcomes in term infants aged 3 to 10 months.MethodsThis was a cohort sub-study within the BabyGel cluster randomised trial in Eastern Uganda. From 1265 term infants screened for CMV, 219 were negative at birth but positive at 3 months, and were age-matched with 219 CMV-negative controls. CMV status was determined by PCR screening of saliva samples, with positive results confirmed using urine samples (Chai Open qPCR, Santa Clara, CA). From the established cohort, 424 infants were successfully followed up between 3 to 10 months of age. Clinical assessments included neurodevelopmental evaluation using the Malawi Developmental Assessment Tool, the Hammersmith Infant Neurological Examination, and hearing screening using Otoacoustic Emission testing (Otoport Lite, Otodynamics Limited). Statistical analyses were performed using descriptive statistics, chi-square tests and log binomial regression models with Stata 18.ResultsOf the 424 infants included in the study, 206 were postnatal CMV-infected and 218 were uninfected. Neurodevelopmental assessments indicated no differences between postnatal CMV-infected infants and uninfected groups (ARR 0.88, 95% CI [0.67, 1.15], p = 0.346). Hearing screening revealed a 1.99-fold increased risk of a positive result for postnatal CMV-infected infants compared to uninfected infants (67/106 vs. 39/106, 95% CI [1.27, 3.12], p = 0.003).ConclusionPostnatal CMV infection was associated with more positive hearing screenings, though no significant differences in neurodevelopmental outcomes were observed in early infancy. Exploration into the feasibility of incorporating hearing and CMV screening into routine care will play a vital role in early identification and intervention, improving the management of both hearing and CMV-related conditions in resource-limited settings.

Project description:BACKGROUNDCongenital cytomegalovirus (cCMV) infection can cause developmental impairment and sensorineural hearing loss (SNHL). To determine the relationship between immune responses to cCMV infection and neurologic sequelae, T cell responses were compared for their connection to clinical symptoms at birth and neurodevelopmental outcomes.METHODSThirty cCMV-infected and 15 uninfected infants were enrolled in a single-center prospective observational case-control study. T cell pp65-specific cytokine responses; CD57, CD28, and PD-1 expression; and memory subsets were compared.RESULTSInfected neonates (73% symptomatic at birth) lacked pp65-specific cytokine-secreting T cells, with elevated frequencies of CD57+, CD28-, and PD-1+CD8+ T cells and effector memory subsets. Though frequencies overlapped between cCMV symptom groups, asymptomatic infants had higher frequencies of CD57+PD-1+CD8+ T cells. Neonates with subsequent developmental delay lacked detectable CMV-specific T cell responses, with patterns resembling those of uninfected infants. Two children with progressive SNHL had high frequencies of PD-1+CD8+ T cells over the first year compared with children without progressive SNHL.CONCLUSIONSimilar to published reports, neonatal viral antigen-specific cytokine-secreting T cell responses were not detected, but overall patterns indicate that globally differentiated memory CD8+ T cell populations were induced by cCMV infection, with higher frequencies of terminally differentiated PD-1+CD8+ T cells potentially associated with asymptomatic infection. In this cohort, a lack of in utero T cell differentiation was associated with developmental delay, and high frequencies of PD-1+CD8+ T cells persisted only in children with progressive SNHL. Further work is needed to define the specificity of these T cells and their mechanistic connection to these outcomes.FUNDINGThis study was funded through an intramural research award at Nationwide Children's Hospital, the Pediatric Infectious Disease Society Fellowship Award funded by Stanley and Susan Plotkin and Sanofi Pasteur, the Abigail Wexner Research Institute at Nationwide Children's Hospital, and the Pichichero Family Foundation Vaccines for Children Initiative Research Award from the Pediatric Infectious Diseases Society Foundation.

Project description:OBJECTIVE:Complementary feeding from the age of 6 months along with breastfeeding is essential for the health of infants. The effect of educational interventions on preventing the early or late onset of complementary feeding and correcting other relevant behaviors depends on the framing of educational messages. This study aimed to compare different types of message framing on maternal behaviors in complementary feeding of infants. MATERIALS AND METHODS:This randomized controlled trial was performed on 96 mothers in three groups of 32 subjects with four-month-old infants in Isfahan (central Iran) during May-September 2018. Data were collected through self-report using a valid researcher-made questionnaire including demographic factors, knowledge, attitude, self-efficacy, and the complementary feeding related behaviors of mothers. For 4 months, the mothers received gain-framed messages in the GF group and loss-framed messages in the LF group from two different channels. The control group only received routine education. Data analysis was performed in SPSS20 using paired t-test, ANOVA, and Chi-square at the significance level of below 0.05. RESULTS:In this study, all three groups were matched in terms of demographic characteristics and mean scores of attitude, knowledge, and self-efficacy regarding the complementary feeding of their infants. Following the intervention, the mean knowledge score increased in all three groups and was more favorable in the intervention groups compared to the control group. However, no difference was observed between the GF and LF groups regarding their knowledge. In addition, the GF and LF groups were similar in terms of self-efficacy and behavior of mothers concerning the appropriate onset of complementary feeding. Meanwhile, the mean scores of attitude and behavior of mothers regarding the timely onset, diversity, and appropriateness of continuing complementary feeding were higher in the LF group compared with the GF group. CONCLUSION:Framing messages changes the attitude and knowledge and improves behaviors related to complementary feeding. The interesting point is the different impacts of different types of framing on psychological and behavioral variables. In general, loss-framed messages have more effects on the attitude and certain parts of maternal behaviors. TRIAL REGISTRATION:IRCT, IRCT20180901040919N1. Registered 29 October 2018, https://en.irct.ir/trial/33782.

Dataset Information

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

Publications

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan.

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