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| Name | Class |
|---|---|
| Cystic Fibrosis Foundation | OTHER |
| Johns Hopkins University | OTHER |
| Massachusetts General Hospital | OTHER |
| National Jewish Health |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| RETRIAL-Mental Health (1st objective - discontinuation): one-year incidence of discontinuation or change from VTD standard dosing due to any reason. | 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. | Baseline to Month 12 |
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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:
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:
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:
RETRIAL-LIVER:
Caregiver Participant:
Inclusion Criteria:
Exclusion Criteria:
- Any situation that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Evelyn Bord, BS | Contact | 617-919-6154 | evelyn.bord@childrens.harvard.edu | |
| Callie Bacon, MPH | Contact | 617-919-7696 | callie.bacon@childrens.harvard.edu |
| Name | Affiliation | Role |
|---|---|---|
| Anna Georgiopoulos, MD | Massachusetts General Hospital | Principal Investigator |
| CJ Bathgate, PhD | National Jewish Health | Principal Investigator |
| Janis Stoll, MD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Recruiting | Birmingham | Alabama | 35233 | United States |
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| OTHER |
| Indiana University | OTHER |
| Children's Hospital Colorado | OTHER |
| University of Kansas Medical Center | OTHER |
| Washington University School of Medicine | OTHER |
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serum, plasma, white blood cells, stool, sputum, DNA
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| 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. |
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| RETRIAL-Neuro | Other | Participants will complete a neurocognitive assessment prior to starting VTD and 28 days after. |
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| 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. | 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). | 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. | 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. | 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. | 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. | Baseline to Month 12 |
| Washington University at St. Louis |
| Principal Investigator |
| Children's Hospital Colorado | Recruiting | Aurora | Colorado | 80045 | United States |
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| National Jewish Health | Recruiting | Denver | Colorado | 80206 | United States |
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| Nemours Children's | Recruiting | Wilmington | Delaware | 19803 | United States |
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| Nemours Children's | Recruiting | Jacksonville | Florida | 32207 | United States |
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| Nemours Children's | Recruiting | Orlando | Florida | 32827 | United States |
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| Nemours Children's | Recruiting | Pensacola | Florida | 32514 | United States |
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| Emory University | Recruiting | Atlanta | Georgia | 30322 | United States |
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| Indiana University | Recruiting | Bloomington | Indiana | 47405 | United States |
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| Kansas University Medical Center | Recruiting | Kansas City | Kansas | 66160 | United States |
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| Johns Hopkins University | Recruiting | Baltimore | Maryland | 21287 | United States |
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| Massachusetts General Hospital | Not yet recruiting | Boston | Massachusetts | 02114 | United States |
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| Boston Children's Hospital | Recruiting | Boston | Massachusetts | 02215 | United States |
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| University of Michigan | Recruiting | Ann Arbor | Michigan | 48109 | United States |
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| Washington University at St. Louis | Not yet recruiting | St Louis | Missouri | 63130 | United States |
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| University of Pittsburgh Medical Center | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
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| University of Texas Southwestern Medical Center | Recruiting | Dallas | Texas | 75235 | United States |
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| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98105 | United States |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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