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

NCT06683092 | Recruiting DMC

• 1 other identifier: IRB-P00050262
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Cystic Fibrosis

Keywords

patient care; adverse events; monitoring

Outcome Measures

Primary Outcomes (4)

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

  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.

  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

  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).

  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.

  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.

  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.

  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.

  Baseline to Month 12

Secondary Outcomes (4)

• 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

Study Arms (3)

RETRIAL-Mental Health

People with CF ages 6 and up with a history of new or worsening mental health symptoms (such as depression, anxiety, mood, sleep) while on elexacaftor/tezacaftor/ivacaftor (ETI) requiring discontinuation or change from standard dosing who start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

Other: RETRIAL-Mental Health

RETRIAL-Neuro

People with CF from RETRIAL-Mental Health who experienced new/worsening neurocognitive symptoms (such as brain fog or memory problems) while taking elexacaftor/tezacaftor/ivacaftor (ETI).

Other: RETRIAL-Neuro

RETRIAL-Liver

People with Cystic Fibrosis ages 6 and up with a history of drug-induced liver injury (such as elevated liver enzymes) attributed to elexacaftor/tezacaftor/ivacaftor (ETI) requiring dose modification or discontinuation who start taking vanzacaftor/tezacaftor/deutivacaftor (VTD).

Other: RETRIAL-Liver

Interventions

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-Mental Health

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-Liver

RETRIAL-Neuro OTHER

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

RETRIAL-Neuro

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Female and male people with CF ages 6 and older who are not able to tolerate the standard dose of ETI due to either new/worsening mental health symptoms and/or drug-induced liver injury.

You may qualify if:

• RETRIAL-Mental Health:
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

National Jewish Health

Denver, Colorado, 80206, United States

RECRUITING

Nemours Children's

Wilmington, Delaware, 19803, United States

RECRUITING

Nemours Children's

Jacksonville, Florida, 32207, United States

RECRUITING

Nemours Children's

Orlando, Florida, 32827, United States

RECRUITING

Nemours Children's

Pensacola, Florida, 32514, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University

Bloomington, Indiana, 47405, United States

RECRUITING

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Washington University at St. Louis

St Louis, Missouri, 63130, United States

NOT YET RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

serum, plasma, white blood cells, stool, sputum, DNA

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Anna Georgiopoulos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• CJ Bathgate, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Janis Stoll, MD

  Washington University at St. Louis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evelyn Bord, BS

CONTACT

617-919-6154; evelyn.bord@childrens.harvard.edu

Callie Bacon, MPH

CONTACT

617-919-7696; callie.bacon@childrens.harvard.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Chair of Success with Therapies Research Consortium

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 12, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: November 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)