Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 15
- 主要终点
- RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening mental health symptoms.
研究概览
简要总结
RETRIAL is a multi-site observational study of people with Cystic Fibrosis (PWCF) ages 6 and up starting the new triple-therapy modulator (vanzacaftor/tezacaftor/deutivacaftor (VTD)), after having experienced neuropsychiatric events and/or liver injury while taking elexacaftor/tezacaftor/ivacaftor (ETI) that resulted in a modification or discontinuation of standard ETI dosing.
详细描述
RETRIAL is a prospective, longitudinal, observational, multi-site study of people with Cystic Fibrosis (PWCF) ages 6 and up who had to either change how they took or stop taking elexacaftor/tezacaftor/ivacaftor (ETI) due to new or worsening mental health/cognitive symptoms (such as depression, anxiety, mood, sleep, and/or brain fog/memory problems) and/or liver issues (elevated liver enzymes) while taking the standard dose, and who plan to start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •RETRIAL-Mental Health:
- •PWCF age 6 years and up (if age is < 12 years old, the PWCF's caregiver will complete daily diaries and surveys; see "Caregiver Participant Inclusion Criteria" below)
- •Eligible for VTD and intending to take it
- •Experienced new or worsening mental health symptoms after initiating ETI, which led to one of the following changes in treatment to currently taking:
- •No modulators
- •A modulator other than ETI
- •A flipped dose of ETI
- •A reduced dose of ETI
- •Willing to delay first VTD dose for short period of time to complete the Baseline assessments
- •Has access to a smart device (phone, tablet, etc.) capable of receiving messages with survey links
- •Is English-speaking.
- •RETRIAL-LIVER:
- •A person with CF age 6 years and up
- •Eligible for VTD and intending to take it
- •Experienced drug-induced liver injury (as defined by local care team) after initiating ETI, which led to one of the following changes in treatment to currently taking:
- •no modulators; or
- •a modulator other than ETI; or
- •a reduced or altered dose of ETI;
- •Willing to delay first VTD dose for short period of time to complete the Baseline assessments
- •Has access to a smart device (phone, tablet, etc.) capable of receiving messages with survey links
- •Is English-speaking.
排除标准
- •RETRIAL-Mental Health:
- •Cannot access VTD
- •Currently, or prior history of, taking VTD
- •Unable or unwilling to follow protocol
- •If <12 years old, having another <12-year-old person in the same household consented into the study
- •Is actively listed on any transplant list, or within 3 months post-transplant surgery
- •Is currently pregnant (test not required)
- •Anticipated change in CF Care Centers in the next 6 months
- •Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
- •RETRIAL-LIVER:
- •Cannot access VTD
- •Currently, or prior history of, taking VTD
- •Unable or unwilling to follow protocol
- •If <12 years old, having another <12-year-old person in the same household consented into the study
- •Any severe, decompensated liver disease (e.g. Child-Pugh, Class C)
- •Is actively listed on any transplant list, or within 3 months post-transplant surgery (any organ), or history of liver transplant
- •Is currently pregnant (test not required)
- •Anticipated change in CF Care Centers in the next 6 months
- •Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
- •Caregiver Participant:
- •Inclusion Criteria:
- •Is a primary, daily caregiver of a person with CF under the age of 12 enrolled in the study
- •Has access to smart device (phone, tablet, etc.) capable of receiving messages with survey links
- •Is able to read and complete surveys and Daily Diary in English.
- •Exclusion Criteria:
- •- Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
结局指标
主要结局
RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening mental health symptoms.
时间窗: Baseline to Month 12
Discontinuation or change from VTD standard dosing due to mental health symptoms at any time during the one-year follow-up as reported in either: daily diaries, biweekly or quarterly surveys, or chart review.
RETRIAL-Mental Health (2nd objective - symptoms): proportion of participants that experience any worsening in mental health symptoms during the 6-month follow-up
时间窗: Baseline to Month 6
Change from baseline that exceeds the minimally-important difference (MID) / minimally-important change (MIC) within the first 6 months after starting VTD in any of the following patient-reported outcome measures: (1) depression (PHQ-8 or PROMIS depression parent proxy), (2) anxiety (GAD-7 or PROMIS anxiety parent proxy), (3) anger and irritability (PROMIS-anger or PROMIS-anger parent proxy), (4) cognitive functioning (PROMIS- cognitive function or PROMIS-cognitive function parent proxy), (5) sleep disturbance (PROMIS-sleep disturbance or PROMIS-sleep disturbance parent proxy).
RETRIAL-Mental Health (3rd objective - RETRIAL-Neuro): proportion of participants that have a worsening on the NIH Toolbox's Fluid Cognition Composite score at 1 month follow-up.
时间窗: Baseline to Day 30
Decrease in age-adjusted standard score from baseline to 1 month on the NIH Toolbox's Fluid Cognition Composite Score (a performance-based neurocognitive measure) that exceeds MIC ≥ 7.5 points, signifying a worsening in function.
RETRIAL-Liver: one-year incidence of drug-induced liver injury (DILI) with VTD, defined by expert consensus after review of clinical and laboratory data.
时间窗: Baseline to Month 12
Positive DILI diagnosis, including those characterized as "likely," "probable," and "highly probable," as reviewed by a hepatology panel of three experts who assign these likelihood scores based upon review of case report forms, including a specific clinical narrative and laboratory values assessing for other potential etiologies.
次要结局
- RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to any reason.(Baseline to Month 12)
- RETRIAL-Mental Health (2nd objective - symptoms): proportion of participants that experience worsening of _each_ mental health symptom during the 6-month follow-up.(Baseline to Month 6)
- RETRIAL-Mental Health (3rd objective - RETRIAL-Neuro): proportion of participants that have a worsening of _each_ of the NIH Toolbox's cognition domain score at 1 month follow-up.(Baseline to Month 1)
- RETRIAL-Liver: one-year incidence of discontinuation or change from VTD standard dosing due to patient-reported or medical team-documented concerns for liver injury.(Baseline to Month 12)
研究者
Gregory Sawicki
Co-Chair of Success with Therapies Research Consortium
Boston Children's Hospital