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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis; Adherence, Medication; Cystic Fibrosis Gastrointestinal Disease; Cystic Fibrosis in Children; Cystic Fibrosis Liver Disease
• Intervention / Treatment: Drug: Elexacaftor/Tezacaftor/Ivacaftor

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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland
    • Children's Health Ireland at Temple Street
  • Dublin, Ireland
    • St. Vincent'S University Hospital
  • Tallaght, Ireland
    • Children's Health Ireland at Tallaght
  • Leinster
    • Dublin, Leinster, Ireland
      • Children's Health Ireland at Crumlin
  • Limerick
    • Limerick, Limerick, Ireland, V94 F858
      • University Hospital Limerick
• United Kingdom
  • Belfast, United Kingdom
    • Royal Belfast Hospital for Sick Children
  • London, United Kingdom
    • Royal Brompton Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard group; The standard testing group will be available for both age cohorts with sites having a predefined recruitment cap for each testing group. The standard testing will involve the following assessments; sweat chloride, LCI, height/weight/BMI, FEV1, airway sampling (micro), FeNO, liver function testing, liver ultrasound, liver examination, stool collection, blood collection, abdominal symptom score, CFQ-R, pharmacy records medication pick up rate, adherence questionnaires, MEMs caps and antibiotic use.	Drug: Elexacaftor/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.
Other: Advanced group; In addition to all elements of the standard testing group, the advanced testing group will undergo: Ultra-low dose spirometry-controlled CT scanning, sputum collection and nasal lavage collection. This will be available for both age cohorts with sites having a predefined recruitment cap for each testing group.	Drug: Elexacaftor/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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LCI on treatment with ETI in children and adults with CF.	Measured using multiple breath washout (MBW)	84 month period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in spirometry-controlled CT scores on treatment with ETI in children and adults with CF.	Spirometry controlled CT	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	84 month period
The change on gastrointestinal symptoms on treatment with ETI in children and adults with CF	Abdominal symptom questionnaire scores	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)	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	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	84 month period
To assess the understanding of disease and experiences with ETI among children and adolescents with CF.	Qualitative Interviews and Drawings	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)	60 month period
Rate of Forced Expiratory Volume in 1 second (FEV1) (L) change on ETI treatment		86 months
Change in microbiology on treatment with ETI in children and adults	Microbiology from clinical swabs and samples	86 months
Change in iron oxide (FeNO) in children and adults with CF	Measured with the Niox VERO device	84 month period
The change in gut inflammation on treatment with ETI in children and adults with CF	Fecal sample - M2PK	84 month period
The change of pancreatic function on treatment with ETI in children and adults with CF	Measured by use of pancreatic enzymes	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	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)	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)	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)	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)	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)	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	60 month period
To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF	Adherence questionnaires	24 month period
To assess the impact of the introduction of ETI on adherence with overall medical treatments for CF	Medication possession ratio (MPR)	24 month period
The change in gut inflammation on treatment with ETI in children and adults with CF	Fecal sample - fecal elastase	84 month period
The change in gut inflammation on treatment with ETI in children and adults with CF	Fecal sample - calprotectin	84 month period

Collaborators and Investigators

• Sponsor: Royal College of Surgeons, Ireland
• Collaborators: The Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin; University of Limerick; St. James's Hospital, Ireland; Teagasc; Cystic Fibrosis Registry of Ireland; Medizinische Hochschule Brandenburg Theodor Fontane; Children's Health Ireland; Amsterdam UMC

Publications and helpful links

General Publications

• McNally P, Lester K, Stone G, Elnazir B, Williamson M, Cox D, Linnane B, Kirwan L, Rea D, O'Regan P, Semple T, Saunders C, Tiddens HAWM, McKone E, Davies JC; RECOVER Study Group. Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial. Am J Respir Crit Care Med. 2023 Nov 1;208(9):917-929. doi: 10.1164/rccm.202308-1317OC.

Helpful Links

• RCOVER Study website
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior; Treatment Adherence and Compliance; Health Behavior; Patient Compliance; Patient Acceptance of Health Care; Cystic Fibrosis; Medication Adherence; elexacaftor, ivacaftor, tezacaftor drug combination
• Other Study ID Numbers: RECOVER

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No