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

Primary Purpose

Cystic Fibrosis, Cystic Fibrosis Liver Disease, Cystic Fibrosis in Children

Status

Active

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Kaftrio

About this trial

This is an interventional other trial for Cystic Fibrosis

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Inclusion criteria People with CF aged 12 years and over: 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 Kaftrio 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 Kaftrio. Participants will receive treatment only through prescription by their physician through usual clinical treatment pathways.

Children aged 6-11 years: Children aged 6-11 years will be included in the study only if and when Kaftrio is licenced, approved and funded for this age group. 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 Kaftrio 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 Kaftrio. Participants will receive treatment only through prescription by their physician through usual clinical treatment pathways.

Subjects on Kaftrio 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 Kaftrio 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 (people with CF aged 12 years and over, children aged 6-11 years and subjects on Kaftrio) must be taking the full dose of Kaftrio (in accordance with the age appropriate posology in the SmPC).

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 Kaftrio 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.

Any contraindication to Katrio treatment as per the local approved SmPC.

Severe hepatic impairment.

Pregnant and breastfeeding women.

Sites / Locations

Children's Health Ireland at Crumlin
Children's Health Ireland at Temple Street
St. Vincent's University Hospital
University Hospital Limerick
Children's Health Ireland at Tallaght
Royal Belfast Hospital for Sick Children
Royal Brompton Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Standard group

Advanced group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

To determine the effect of treatment with TCMT on pulmonary function (FEV1 and LCI) in children and adults with CF over a period of 2 years.

Spirometry, LCI

Secondary Outcome Measures

To determine the effect of treatment with TCMT on spirometry-controlled CT scores in children and adults with CF over a two-year period.

Spirometry controlled CT

To determine the effect of treatment with TCMT on airway infection and inflammation in children and adults with CF

Sputum sample collection, Nasal lavage, airway sampling (microbiology), Sinus sypmptoms (CFQ-R), FeNO

To determine the effect of treatment with TCMT on nutrition, gastrointestinal symptoms, gut inflammation and pancreatic function in children and adults with CF over a two-year period

Abdominal symptom questionnaire, fecal sample, liver examination, liver ultrasound, liver function tests

To determine the effect of treatment with TCMT on antibiotic treatment of pulmonary disease in children and adults with CF over a two-year period

Medication possession ratio (MPR)

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

MEMs caps, adherence questionnaires, Medication possession ratio (MPR)

Full Information

NCT ID

NCT04602468

First Posted

October 20, 2020

Last Updated

August 29, 2023

Sponsor

Royal College of Surgeons, Ireland

Collaborators

Imperial College London, University College Dublin, University of Limerick, Cystic Fibrosis Registry of Ireland, Erasmus Medical Center, Medizinische Hochschule Brandenburg Theodor Fontane, Queen's University, Belfast, Teagasc, The Hospital for Sick Children, St. James's Hospital, Ireland, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

1. Study Identification

Unique Protocol Identification Number

NCT04602468

Brief Title

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

Acronym

RECOVER

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 3, 2020 (Actual)

Primary Completion Date

December 1, 2023 (Anticipated)

Study Completion Date

July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Royal College of Surgeons, Ireland

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RECOVER is a prospective, multicenter observational study designed to measure the real world clinical effectiveness of elexacaftor, tezacaftor and ivacaftor triple combination therapy (Kaftrio) in people with cystic fibrosis over a two year 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 children aged six years and above over a period of two years. The first phase of the study will commence in 2020, recruiting children 12 years and older who have started on clinical treatment with Kaftrio.

Detailed Description

Our aim with RECOVER is to examine the clinical impact of Kaftrio 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, we 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, we will have the power to gain important insight into how Kaftrio 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) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis, Cystic Fibrosis Liver Disease, Cystic Fibrosis in Children, Adherence, Medication, Cystic Fibrosis Gastrointestinal Disease

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Model Description

The decision to implement Kaftrio treatment is made completely independently of the decision to enter the study. The investigators will follow the requirements of the local approved Kaftrio 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 Kaftrio will only occur in the context of prescription by a physician in compliance with marketing authorization and the SPC.

Masking

Participant

Masking Description

No blinding. The decision to implement Kaftrio treatment is made completely independently of the decision to enter the study. Those determined to begin treatment on Kaftrio clinically will undergo eligibility assessment.

Allocation

Non-Randomized

Enrollment

237 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard group

Arm Type

Other

Arm Description

Arm Title

Advanced group

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Kaftrio

Other Intervention Name(s)

Trikafta

Intervention Description

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.

Primary Outcome Measure Information:

Title

To determine the effect of treatment with TCMT on pulmonary function (FEV1 and LCI) in children and adults with CF over a period of 2 years.

Description

Spirometry, LCI

Time Frame

24 month period

Secondary Outcome Measure Information:

Title

To determine the effect of treatment with TCMT on spirometry-controlled CT scores in children and adults with CF over a two-year period.

Description

Spirometry controlled CT

Time Frame

24 month period

Title

To determine the effect of treatment with TCMT on airway infection and inflammation in children and adults with CF

Description

Sputum sample collection, Nasal lavage, airway sampling (microbiology), Sinus sypmptoms (CFQ-R), FeNO

Time Frame

24 month period

Title

To determine the effect of treatment with TCMT on nutrition, gastrointestinal symptoms, gut inflammation and pancreatic function in children and adults with CF over a two-year period

Description

Abdominal symptom questionnaire, fecal sample, liver examination, liver ultrasound, liver function tests

Time Frame

24 month period

Title

To determine the effect of treatment with TCMT on antibiotic treatment of pulmonary disease in children and adults with CF over a two-year period

Description

Medication possession ratio (MPR)

Time Frame

24 month period

Title

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

Description

MEMs caps, adherence questionnaires, Medication possession ratio (MPR)

Time Frame

24 month period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Inclusion criteria People with CF aged 12 years and over: 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 Kaftrio 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 Kaftrio. Participants will receive treatment only through prescription by their physician through usual clinical treatment pathways. Children aged 6-11 years: Children aged 6-11 years will be included in the study only if and when Kaftrio is licenced, approved and funded for this age group. 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 Kaftrio 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 Kaftrio. Participants will receive treatment only through prescription by their physician through usual clinical treatment pathways. Subjects on Kaftrio 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 Kaftrio 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 (people with CF aged 12 years and over, children aged 6-11 years and subjects on Kaftrio) must be taking the full dose of Kaftrio (in accordance with the age appropriate posology in the SmPC). 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 Kaftrio 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. Any contraindication to Katrio treatment as per the local approved SmPC. Severe hepatic impairment. Pregnant and breastfeeding women.

Facility Information:

Facility Name

Children's Health Ireland at Crumlin

City

Dublin

State/Province

Leinster

Country

Ireland

Facility Name

Children's Health Ireland at Temple Street

City

Dublin

Country

Ireland

Facility Name

St. Vincent's University Hospital

City

Dublin

Country

Ireland

Facility Name

University Hospital Limerick

City

Limerick

ZIP/Postal Code

V94 F858

Country

Ireland

Facility Name

Children's Health Ireland at Tallaght

City

Tallaght

Country

Ireland

Facility Name

Royal Belfast Hospital for Sick Children

City

Belfast

Country

United Kingdom

Facility Name

Royal Brompton Hospital

City

London

Country

United Kingdom

12. IPD Sharing Statement

Links:

URL

https://recovercf.ie/

Description

RCOVER Study website

URL

https://twitter.com/StudyCf

Description

RECOVER Twitter Account

Learn more about this trial

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

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