Real World Clinical Outcomes With Novel Modulator Therapy Combinations in People With CF (RECOVER)

Phase 4Active Not RecruitingNCT04602468

Royal College of Surgeons, Ireland206 enrolled

Overview

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.

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.

Study Type

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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.

Locations (7)

Children's Health Ireland at Crumlin

Dublin, Leinster, Ireland

University Hospital Limerick

Limerick, Limerick, Ireland

Children's Health Ireland at Temple Street

Dublin, Ireland

St. Vincent's University Hospital

Dublin, Ireland

Children's Health Ireland at Tallaght

Tallaght, Ireland

Royal Belfast Hospital for Sick Children

Belfast, United Kingdom

Royal Brompton Hospital

London, United Kingdom

Outcomes

Primary Outcomes

Change in LCI on treatment with ETI in children and adults with CF.

Measured using multiple breath washout (MBW)

Time frame: 84 month period

Secondary Outcomes

The change in spirometry-controlled CT scores on treatment with ETI in children and adults with CF.

Spirometry controlled CT

Time frame: 84 month period

Change in airway inflammation markers in children and adults with CF

Change in NE, SLPI and IL-8 (pg/ml) concentration sputum and nasal lavage

Time frame: 84 month period

The change on gastrointestinal symptoms on treatment with ETI in children and adults with CF

Abdominal symptom questionnaire scores

Time frame: 84 month period

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

Medication possession ratio (MPR)

Time frame: 24 month period

To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF

Medication Event Monitoring (MEM) caps

Time frame: 24 month period

To determine the effect of treatment with TCM on CF liver disease in children and adults with CF

Ultrasound and liver function test

Time frame: 84 month period

To assess the understanding of disease and experiences with ETI among children and adolescents with CF.

Qualitative Interviews and Drawings

Time frame: Up to year 1

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

Patient Health Questionnaire - 9 (PHQ-9)

Time frame: 60 month period

Rate of Forced Expiratory Volume in 1 second (FEV1) (L) change on ETI treatment

Time frame: 86 months

Change in microbiology on treatment with ETI in children and adults

Microbiology from clinical swabs and samples

Time frame: 86 months

Change in iron oxide (FeNO) in children and adults with CF

Measured with the Niox VERO device

Time frame: 84 month period

The change in gut inflammation on treatment with ETI in children and adults with CF

Fecal sample - M2PK

Time frame: 84 month period

The change of pancreatic function on treatment with ETI in children and adults with CF

Measured by use of pancreatic enzymes

Time frame: 84 month period

To assess the understanding of disease and experiences with ETI among children and adolescents with CF.

Patient Health Questionnaire 9 (PHQ-9)-Modified for Adolescents

Time frame: Up to year 1

To assess the understanding of disease and experiences with ETI among children and adolescents with CF.

Generalised Anxiety Disorder 7 (GAD-7)

Time frame: Up to year 1

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

Generalized Anxiety Disorder -7 (GAD-7)

Time frame: 60 month period

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

PROMIS Pediatric Anxiety Scale (Short Form - 8a)

Time frame: 60 month period

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

Depressed Mood Scale (Short Form - 8a)

Time frame: 60 month period

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

PROMIS Pediatric Cognitive Function Scale (Short Form 7a)

Time frame: 60 month period

To determine the longitudinal changes in mental health outcomes associated with the use of TCM in children and adults with CF.

RECOVER Body image questionnaire

Time frame: 60 month period

To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF

Adherence questionnaires

Time frame: 24 month period

To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF

Medication possession ratio (MPR)

Time frame: 24 month period

The change in gut inflammation on treatment with ETI in children and adults with CF

Fecal sample - fecal elastase

Time frame: 84 month period

The change in gut inflammation on treatment with ETI in children and adults with CF

Fecal sample - calprotectin

Time frame: 84 month period

Real World Clinical Outcomes With Novel Modulator Therapy Combinations in People With CF (RECOVER)

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes