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NCT Number: NCT06683092

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

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.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

6 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

RETRIAL-Mental Health

Other

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).

RETRIAL-Liver

Other

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.

RETRIAL-Neuro

Other

Participants will complete a neurocognitive assessment prior to starting VTD and 28 days after.

Primary outcomes

  1. RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening mental health symptoms.

    Time frame: 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.

  2. RETRIAL-Mental Health (2nd objective - symptoms): proportion of participants that experience any worsening in mental health symptoms during the 6-month follow-up

    Time frame: 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).

  3. 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.

    Time frame: 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.

  4. RETRIAL-Liver: one-year incidence of drug-induced liver injury (DILI) with VTD, defined by expert consensus after review of clinical and laboratory data.

    Time frame: 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.

Secondary outcomes

  1. RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to any reason.

    Time frame: Baseline to Month 12

    Reported discontinuation or change from VTD standard dosing due to any reason during the one-year follow-up as reported in either: daily diaries, biweekly or quarterly surveys, or chart review.

  2. RETRIAL-Mental Health (2nd objective - symptoms): proportion of participants that experience worsening of _each_ mental health symptom during the 6-month follow-up.

    Time frame: Baseline to Month 6

    Change from baseline that exceeds the MID/MIC of new/worsening symptoms within the first 6 months after starting VTD for _each_ of the following patient-reported outcomes: (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).

  3. 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.

    Time frame: Baseline to Month 1

    Decrease in age-adjusted standard score from baseline to 1-month that exceeds MIC ≥ 7.5 points for _each_ of the following domains: (1) Flanker, (2) Dimensional Change Card Sort (DCCS), (3) Picture Sequence Memory Test (PSMT), (4) List Sorting, (5) Pattern Comparison.

  4. 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.

    Time frame: Baseline to Month 12

    Reported discontinuation or change from VTD standard dosing due to concerns for liver injury during the one-year follow-up as reported in either: 28-day or quarterly surveys, chart review, or case report forms.

Study contacts

Contact information is provided by the study sponsor or research team.

Callie Bacon, MPH

CONTACT

[email protected]

617-919-7696

Evelyn Bord, BS

CONTACT

[email protected]

617-919-6154

Sponsors and collaborators

Lead sponsor

Boston Children's Hospital

Other

Collaborators

  • Children's Hospital Colorado
  • Cystic Fibrosis Foundation
  • Indiana University
  • Johns Hopkins University
  • Massachusetts General Hospital
  • National Jewish Health
  • University of Kansas Medical Center
  • Washington University School of Medicine

Registry information

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Nov 12, 2024
Registry last updated
Nov 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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