Cystic Fibrosis
Conditions
Keywords
patient care, adverse events, monitoring
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.
Detailed description
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).
Interventions
OTHERRETRIAL-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).
OTHERRETRIAL-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.
OTHERRETRIAL-Neuro
Participants will complete a neurocognitive assessment prior to starting VTD and 28 days after.
Sponsors
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
Boston Children's Hospital
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RETRIAL-Liver: one-year incidence of drug-induced liver injury (DILI) with VTD, defined by expert consensus after review of clinical and laboratory data. | 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. |
| RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to new/worsening mental health symptoms. | 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 | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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). |
| 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 | 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. |
| 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 | 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. |
Countries
United States
Contacts
Primary ContactEvelyn Bord, BS
Backup ContactCallie Bacon, MPH
Outcome results
None listed