NCT06683092 · Boston Children's Hospital
Restarting Triple Therapy With Robust Monitoring for Adverse Events (RETRIAL)
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
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).
OTHER
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.
OTHER
RETRIAL-Neuro
Participants will complete a neurocognitive assessment prior to starting VTD and 28 days after.
Primary outcome measures
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.
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).
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.
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Birmingham, Alabama
- Aurora, Colorado
- Denver, Colorado
- Wilmington, Delaware
- Jacksonville, Florida
- Orlando, Florida
- Pensacola, Florida
- Atlanta, Georgia
- Bloomington, Indiana
- Kansas City, Kansas
- Baltimore, Maryland
- Boston, Massachusetts
And 5 more locations — see the full list below.
Collaborators
Cystic Fibrosis Foundation, Johns Hopkins University, Massachusetts General Hospital, National Jewish Health, Indiana University, Children's Hospital Colorado, University of Kansas Medical Center, Washington University School of Medicine
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Nov 3, 2025 · Source of record for eligibility and locations