Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 60
- 主要终点
- Total Ear Hearing Slope
研究概览
简要总结
The overall goal of this study is to determine the clinical benefit and safety of antiviral therapy for asymptomatic congenital cytomegalovirus (cCMV) infected hearing-impaired infants. We will conduct a multi-center double-blind randomized placebo-controlled trial to determine whether hearing-impaired infants with asymptomatic cCMV have better hearing and language outcomes if they receive valganciclovir antiviral treatment. We will also determine the safety of antiviral valganciclovir therapy for asymptomatic cCMV-infected hearing impaired infants. This study will be unique in that the cohort enrolled will only include hearing-impaired infants with asymptomatic cCMV.
Primary Objective: To determine if treatment of cCMV-infected hearing impaired infants with isolated hearing loss with the antiviral drug valganciclovir reduces the mean slope of total hearing thresholds over the 20 months after randomization compared to untreated cCMV-infected infants with isolated hearing loss.
Main Secondary Objectives:
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To determine if valganciclovir treatment improves the following outcomes when compared to the control group:
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The slope of best ear hearing thresholds over the 20 months after randomization.
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The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 20 months of age.
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To evaluate safety measures based on all grade 3 or greater new adverse events designated by the NIAID Division of AIDS (DAIDS) toxicity tables.
详细描述
Cytomegalovirus (CMV) can be transmitted from the mother to the fetus and is a leading cause of sensorineural hearing loss (SNHL), which is a condition where the inner ear is unable to convert sound into nerve impulses to the brain. This hearing loss and its detrimental effect on language development contribute nearly $4 billion annually to the health care costs in the U.S. Unlike other types of SNHL, CMV induced hearing loss can be treated. Several clinical trials have demonstrated that antiviral therapy may prevent progressive hearing loss if administered early in life for severely affected (symptomatic CMV) infants. These promising findings have given rise to a debate regarding the best method for identifying and treating the more numerous asymptomatic CMV-infected infants.
One approach is to conduct universal newborn hearing screens, and then do CMV diagnostic testing only on the infants who fail the hearing screen. This targeted approach should identify those infants at greatest risk of developing progressive hearing loss and consequent communicative difficulties. Utah is the first state to mandate this approach whereby infants under three weeks of age who fail their newborn hearing screening undergo CMV testing. In this trial, the hearing screen targeted approach will be used to identify patients eligible for participation in a double blind placebo controlled randomized clinical trial of antiviral valganciclovir therapy. The results of this trial will inform public policy, potentially shift our current clinical practice regarding pediatric hearing loss evaluation, and potentially offer a therapeutic option to asymptomatic CMV-infected infants with SNHL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo and active drug will be dispensed in identical amber bottles with identical labeling.
入排标准
- 年龄范围
- 1 Month 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than or equal to 1 month and less than or equal to 12 months at the time of randomization; AND
- •Positive congenital CMV by urine culture or polymerase chain reaction test(PCR), OR saliva culture or PCR followed by confirmatory urine PCR by 21 days of age, OR urine culture or PCR after 21 days of age followed by newborn dry blood spot PCR; AND
- •Confirmed sensorineural hearing loss (SNHL) by auditory brainstem response (ABR) testing. For ABR assessments, hearing loss is defined as levels greater than 25 dB normal hearing levels (NHL) at 1, 2, or 4 kHz in one or both ears.
排除标准
- •Imminent demise; OR
- •Known hypersensitivity reaction to valganciclovir, ganciclovir, or any components of the investigational product formulation; OR
- •ALT (Alanine Aminotransferase) five times baseline U/L, hepatomegaly, or significant gastrointestinal disorders (e.g., eosinophilic esophagitis, ulcerative colitis); OR
- •Absolute neutrophil count (ANC) less than 500 cells/mm^3, Hemoglobin less than 8 g/dL, or platelets less than 50,000/mm^3, splenomegaly, or significant hematologic disorders (e.g., hemophilia, leukemia, sickle cell anemia); OR
- •Creatinine clearance less than 60 mL/min/1.73m^2 or significant renal disorders (e.g., nephrotic syndrome); OR
- •Receiving other antiviral medications or immune globulin therapy; OR
- •Receiving other investigational drugs; OR
- •Breast feeding from a mother receiving antiviral or immunosuppressive medication; OR
- •Known HIV positive mother (risk of immunosuppression); OR
- •Subject is currently using list of prohibited medication specified by the package insert; OR
- •Other known cause contributing to SNHL (e.g., meningitis, aminoglycoside ototoxicity); OR
- •Bilateral profound SNHL or auditory neuropathy spectrum disorder; OR
- •Existing conductive hearing loss or mixed permanent hearing loss is present; OR
- •Evidence of intracranial calcification; OR
- •Evidence of hydrocephalus; OR
- •Microcephaly; OR
- •Presence of petechiae; OR
- •Intrauterine growth retardation; OR
- •Chorioretinitis, optic atrophy or pale optic nerves; OR
- •Parent or guardian unable to speak English or Spanish; OR
- •Subject exposed to a language other than English or Spanish a majority of the time; OR
- •Subject unable to complete hearing assessments or parent/guardian unable to complete communication questionnaires; OR
- •< 32 weeks gestational age at birth; OR
- •Weight at the time of birth < 1800 g.
研究组 & 干预措施
Arm A
Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months
干预措施: Valganciclovir (Drug)
Arm B
Flavored Simple Syrup, volume equivalent to active arm dose, PO BID x 6 months
干预措施: Simple Syrup (Drug)
结局指标
主要结局
Total Ear Hearing Slope
时间窗: Assessed at baseline, 8, 14 and 20 months post-randomization
The primary objective of this randomized trial is to determine if treatment of cCMV-infected infants with isolated hearing loss with the antiviral drug valganciclovir reduces the slope of the total ear hearing thresholds over the 20 months after randomization compared to that of untreated cCMV-infected infants with isolated hearing loss.
Baseline Total Ear Hearing Thresholds
时间窗: Baseline assessment
Baseline hearing thresholds were summarized descriptively using the average minimum response levels (MRLs) at 2 kHz and 4 kHz for each ear. Lower values indicate better hearing sensitivity.
次要结局
- Percentile Score for Words Produced Endpoint(Assessed at 20 months of age)
- Best Ear Hearing Slope(Assessed at baseline, 8, 14 and 20 months post-randomization)
- Baseline Best-Ear Hearing Thresholds (2 kHz and 4 kHz)(Baseline assessment)
- MacArthur-Bates Communicative Development Inventories (CDI): Words Produced Percentile Score(20 months of age)
研究者
Albert Park
Chief Peds Otolaryngology
University of Utah