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Restarting triple modulator therapy with close safety monitoring

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

Observational Boston Children's Hospital · NCT06683092

This project tests whether people with cystic fibrosis aged 6 and up who stopped or changed elexacaftor/tezacaftor/ivacaftor (ETI) because of mental health or liver problems can start vanzacaftor/tezacaftor/deutivacaftor (VTD) safely with close monitoring.

Quick facts

Study typeObservational
Enrollment200 (estimated)
Ages6 Years and up
SexAll
SponsorBoston Children's Hospital Academic / other
Locations18 sites (Birmingham, Alabama and 17 other locations)
Trial IDNCT06683092 on ClinicalTrials.gov

What this trial studies

RETRIAL is a prospective, longitudinal, observational, multi-site effort enrolling people with cystic fibrosis age 6 and older who modified or stopped ETI because of new or worsening neuropsychiatric symptoms or liver injury and who plan to start VTD. Participants are followed over time with daily diaries, periodic surveys delivered to smart devices, and targeted mental health and liver monitoring to detect adverse events. The protocol includes sub-cohorts focused on mental health, liver, and neuro outcomes and requires a brief baseline assessment before restarting VTD. Data are collected across multiple U.S. CF centers to describe safety signals and patterns after restarting triple-modulator therapy.

Who should consider this trial

Good fit: Ideal candidates are people with cystic fibrosis age 6 or older who are eligible for VTD, who previously changed or stopped ETI because of new or worsening mental health or liver issues, and who can complete baseline testing, use a smart device, and participate at a study site or via remote follow-up.

Not a fit: Patients unlikely to benefit include those without prior ETI-related neuropsychiatric or liver events, those not eligible for VTD, or those unable to comply with device-based surveys, English-language participation, or follow-up at participating sites.

Why it matters

Potential benefit: If successful, this could help clinicians and patients restart triple-modulator therapy more safely by identifying who tolerates VTD and how best to monitor for recurring mental health or liver problems.

How similar studies have performed: There are case reports and small case series suggesting some patients improve after switching or adjusting modulators, but prospective multi-site data on systematic restarts with intensive monitoring remain limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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:

  1. No modulators
  2. A modulator other than ETI
  3. A flipped dose of ETI
  4. 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:

  1. no modulators; or
  2. a modulator other than ETI; or
  3. 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 this trial is running

Birmingham, Alabama and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Cystic Fibrosispatient careadverse eventsmonitoring
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.