Adherence, Medication, Cystic Fibrosis, Cystic Fibrosis Gastrointestinal Disease, Cystic Fibrosis in Children, Cystic Fibrosis Liver Disease
Conditions
Brief summary
RECOVER is a prospective, multicenter observational study designed to measure the real world clinical effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) triple combination therapy in people with cystic fibrosis initially over a two year period, followed by a five year extension period. Measured outcomes include measures of lung function, lung inflammation, lung imaging, abdominal symptoms, gut inflammation, liver function, pancreatic exocrine function, nasal inflammation, quality of life and adherence to therapy. The study will examine outcomes in two cohorts, children aged six to eleven years and children and adults aged twelve and above.
Detailed description
Our aim with RECOVER is to examine the clinical impact of ETI on key clinical outcomes in people with CF in a real-world setting. For this study, in addition to some of the more traditional ways of monitoring clinical outcomes in people with CF such a standard lung function, nutrition, exacerbations and liver disease, the investigators are proposing to include some novel outcome measures not typically used in clinical trials such as lung clearance index (LCI) and spirometry controlled chest CT. By implementing an extensive study protocol that will include important outcomes in a number of areas of health in people with CF, and matching this to a comprehensive biosample collection plan, the investigators will have the power to gain important insight into how ETI works, and what impact it has on rescue of CFTR function in this group of people. Data on the following outcomes will be collected during the study: Lung Clearance Index Ultra-low dose, spirometry-controlled CT scanning Sweat Chloride Nasal Lavage (inflammatory markers and microbiome) Fraction of Exhaled Nitric Oxide (FeNO) Liver Ultrasound Liver examination (signs of liver disease) Sputum Collection (inflammatory markers and microbiome) Stool Collection (inflammation, microbiome, fecal elastase) Abdominal symptom questionnaire CFQ-R (quality of life) Adherence to treatment Height, weight, BMI Forced Expiratory volume in 1 second (FEV1) Microbiological culture of airway specimens (clinical laboratories at sites) Mental Health outcomes The Lead Investigator is Paul McNally, with Prof. Jane Davies as Co-Lead Investigator. The study will operate in collaboration with our academic and clinical partners and the CF registries in Ireland and the UK. The study is supported by the European CF Society Clinical Trials Network (ECFS-CTN). The study is being run as a CTIMP in the UK clinical sites, as determined by the MHRA. In the Irish sites, the HPRA has determined this study to be an observational research study.
Interventions
DRUGElexacaftor/Tezacaftor/Ivacaftor
The intervention is the same for both study groups. In addition to all the assessments in the standard arm, the advanced arm subjects will undergo spirometry controlled CT, nasal lavage and sputum sample collection.
Sponsors
Royal College of Surgeons, Ireland
Imperial College London
University College Dublin
University of Limerick
Cystic Fibrosis Registry of Ireland
Erasmus Medical Center
Medizinische Hochschule Brandenburg Theodor Fontane
Teagasc
The Hospital for Sick Children
St. James's Hospital, Ireland
Amsterdam UMC
Children's Health Ireland
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
No blinding. The decision to implement ETI treatment is made completely independently of the decision to enter the study. Those determined to begin treatment on ETI clinically will undergo eligibility assessment.
Intervention model description
The decision to implement ETI treatment is made completely independently of the decision to enter the study. The investigators will follow the requirements of the local approved ETI SmPC for the patient management as detailed in the 'special warnings and precautions for use' (e.g. management of hepatic impairment, rash, ophthalmological monitoring, between others), and for the management of interaction with other medicinal products and other forms of interactions. The 12+ cohort will be enrolled first on the basis the drug will be approved for children aged 12 and over first. The 6-11 year cohort will only be enrolled when the license is extended to this age group, and treatment with ETI will only occur in the context of prescription by a physician in compliance with marketing authorization and the SPC.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants may only be selected for inclusion in RECOVER if they have been independently determined by their treating physician to be suitable for treatment with ETI in compliance with the official marketing authorization and summary of product characteristics (SPC). The decision to include participants in the study is independent of decision to prescribe ETI. Participants will receive treatment only through prescription by their physician through usual clinical treatment pathways. Subjects on ETI In exceptional circumstances where baseline clinical data has been collected prior to the start of treatment either through clinical care or ethically approved research projects (including a cohort of subjects initially recruited to this study on the understanding that it was a non-regulated observational study) subjects already receiving ETI may be recruited to this study and undergo on-treatment visits. Any additional patient data can only be added with written informed consent from the patients/parents concerned. All subjects must have a signed informed consent form and/or signed assent form when appropriate, as determined by the subjects age and individual site and country standards. Male and female participants of childbearing potential must agree to adhere to contraception requirements as detailed in the local ETI SmPC and in line with the standard of care.
Exclusion criteria
Patients not willing to comply with study procedures or assessments. Individuals on clinical trials of investigational CFTR modulators. Clinical instability at baseline assessments. Subjects undergoing an active exacerbation and at the beginning of their treatment should be excluded from the study as this is likely to skew the data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in LCI on treatment with ETI in children and adults with CF. | 84 month period | Measured using multiple breath washout (MBW) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change on gastrointestinal symptoms on treatment with ETI in children and adults with CF | 84 month period | Abdominal symptom questionnaire scores |
| To determine the effect of treatment with ETI on antibiotic treatment of pulmonary disease in children and adults with CF over a two-year period | 24 month period | Medication possession ratio (MPR) |
| To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF | 24 month period | Medication Event Monitoring (MEM) caps |
| To determine the effect of treatment with TCM on CF liver disease in children and adults with CF | 84 month period | Ultrasound and liver function test |
| To assess the understanding of disease and experiences with ETI among children and adolescents with CF. | Up to year 1 | Qualitative Interviews and Drawings |
| To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF. | 60 month period | Patient Health Questionnaire - 9 (PHQ-9) |
| Change in airway inflammation markers in children and adults with CF | 84 month period | Change in NE, SLPI and IL-8 (pg/ml) concentration sputum and nasal lavage |
| Change in microbiology on treatment with ETI in children and adults | 86 months | Microbiology from clinical swabs and samples |
| Change in iron oxide (FeNO) in children and adults with CF | 84 month period | Measured with the Niox VERO device |
| The change in gut inflammation on treatment with ETI in children and adults with CF | 84 month period | Fecal sample - M2PK |
| The change of pancreatic function on treatment with ETI in children and adults with CF | 84 month period | Measured by use of pancreatic enzymes |
| The change in spirometry-controlled CT scores on treatment with ETI in children and adults with CF. | 84 month period | Spirometry controlled CT |
| Rate of Forced Expiratory Volume in 1 second (FEV1) (L) change on ETI treatment | 86 months | — |
Countries
Ireland, United Kingdom
Outcome results
None listed