Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)

Обзор

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.

Подробное описание

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).

Вмешательства

• Другое RETRIAL-Mental Health
  Participants will complete: daily diaries for 6 weeks, from about 2 weeks prior to starting VTD to about 4 weeks after; biweekly surveys, from about 2 weeks prior to starting VTD to 6 months after, and 2 quarterly surveys (at 9mo and 12mo post-initiation of VTD).
• Другое RETRIAL-Liver
  Participants may have a research liver function test done prior to starting VTD and 28 days after, if not done clinically. Participants will complete surveys: before starting VTD, a month after, and quarterly (at about 3, 6, 9, and 12 months) following VTD initiation.
• Другое RETRIAL-Neuro
  Participants will complete a neurocognitive assessment prior to starting VTD and 28 days after.

Первичные конечные точки

• RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening mental health symptoms. [Срок оценки: Baseline to Month 12]
• RETRIAL-Mental Health (2nd objective - symptoms): proportion of participants that experience any worsening in mental health symptoms during the 6-month follow-up [Срок оценки: Baseline to Month 6]
• 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. [Срок оценки: Baseline to Day 30]
• RETRIAL-Liver: one-year incidence of drug-induced liver injury (DILI) with VTD, defined by expert consensus after review of clinical and laboratory data. [Срок оценки: Baseline to Month 12]

Вторичные конечные точки (4)

• RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to any reason. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: Baseline to Month 12]

Критерии участия

Критерии включения

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.

Критерии исключения

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:

Критерии включения

• 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.

Критерии исключения

\- Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 18 центров

• University of Alabama at Birmingham — Birmingham
• Children's Hospital Colorado — Aurora
• National Jewish Health — Denver
• Nemours Children's — Wilmington
• Nemours Children's — Jacksonville
• Nemours Children's — Orlando
• Nemours Children's — Pensacola
• Emory University — Atlanta
• … и ещё 10 центров

Идентификаторы

NCT: NCT06683092 · IRB-P00050262

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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