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

Boston Children's Hospital

Status: Enrolling

Conditions: Cystic Fibrosis

Treatments: Other: RETRIAL-Mental Health; Other: RETRIAL-Liver; Other: RETRIAL-Neuro

Study type: Observational

Funder types: Other

Identifiers

NCT06683092

IRB-P00050262

Details and patient eligibility

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.

Full 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).

Enrollment: 200 estimated patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 3 patient groups

RETRIAL-Mental Health

Description:

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).

Treatment:

Other: RETRIAL-Mental Health

RETRIAL-Neuro

Description:

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).

Treatment:

Other: RETRIAL-Neuro

RETRIAL-Liver

Description:

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).

Treatment:

Other: RETRIAL-Liver