Condition category
Nutritional, Metabolic, Endocrine
Date applied
22/10/2020
Date assigned
16/12/2020
Last edited
16/12/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Cystic fibrosis is an inherited condition that causes sticky mucus to build up in the lungs and digestive system. This causes lung infections and problems with digesting food.
In recent years, a number of new exciting medications have been developed that treat the underlying genetic defect in Cystic fibrosis (CF).
In August 2020 the next generation of potent CF medications Tezacaftor/Ivacaftor/Elexacaftor (Kaftrio) was approved for patients with CF in Europe (having previously been approved by the FDA. This presents a unique opportunity for us to plan a real world study involving all Irish centres in people six years and above with CF.

Who can participate?
People with cystic fibrosis that are suitable for treatment with triple combination modulator therapy can partake in this study.

What does the study involve?
The study will examine clinical outcomes over a two-year period for each age cohort (6-11 years and 12+ years) across eight pediatric and adult CF centers in Ireland and the UK. Participants will be prescribed Kaftrio for 24 months. They will attend appointments to provide measurements at the start of the study and then every 3 months until the end of the study.

What are the possible benefits and risks of participating?
The subject may benefit from the information obtained during the study. Depending on the usual practice of performing tests and investigations at your local centre, the subject may have more diagnostic tests performed that can be used by the local team. People in research studies see their CF team more than those not involved in research studies. This could be associated with better outcomes.
Almost all medical investigations and treatments have some risks. The following tests are associated with mild discomfort: Nasal lavage (irritating, like doing a nasal rinse). Sputum induction – subject is encouraged to cough after having nebulised hypertonic saline (can cause excessive coughing). Blood tests (we will endeavour to collect blood for RECOVER only when it is already needed for clinical care - two RECOVER blood tests, at baseline and year one).
The subject may have CT scans as part of the advanced tests required for this study. They would not have these scans if they did not take part in the study. These procedures use ionising radiation to form images of the lungs. Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. We are all at risk of developing cancer during our lifetime. This will happen to about 50% of people at some point in their life. Taking part in this study will increase the chances of this happening from 50% to 50.1 %.

Where is the study run from?
RECOVER will be co-ordinated through the Royal College of Surgeons in Ireland.

When is the study starting and how long is it expected to run for?
January 2020 to June 2024

Who is funding the study?
1. Cystic Fibrosis Foundation (USA)
2. Cystic Fibrosis Trust (UK)
3. Cystic Fibrosis Ireland

Who is the main contact?
RECOVER study team, info@recovercf.ie
RECOVER project manager, Aine Fleming, ainefleming@rcsi.ie

Trial website

https://recovercf.ie/

Contact information

Type

Public

Primary contact

Ms Aine Fleming

ORCID ID

Contact details

National Children's Research Centre
Gate 5
Children's Health Ireland at Crumlin
Cooley Road
Dublin
D12 N512
Ireland
+353 (0)872147416
ainefleming@rcsi.ie

Type

Scientific

Additional contact

Prof Jane Davies

ORCID ID

http://orcid.org/0000-0003-3506-1199

Contact details

Imperial College London and Royal Brompton and Harefield NHS Foundation Trust
Sydney St.
Chelsea
London
SW3 6NP
United Kingdom
+44 (0)20 7594 7973
j.c.davies@imperial.ac.uk

Type

Scientific

Additional contact

Prof Paul McNally

ORCID ID

http://orcid.org/0000-0001-7102-1712

Contact details

Royal College of Surgeons in Ireland
Children's Health Ireland at Crumlin
Cooley Road
Dublin
D12 N512
Ireland
+353 (1)4096500
paulmcnally@rcsi.ie

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRAS 279116

Study information

Scientific title

Real world clinical outcomes with novel modifier therapy combinations in people with cystic fibrosis

Acronym

RECOVER

Study hypothesis

1. Use of TCMT in routine clinical practice is associated with significant and sustained improvements in airway and gastrointestinal outcomes and quality of life in children and adults with cystic fibrosis
2. Adherence to routine therapies will decrease after initiation of TCMT

Ethics approval

1. Approved 21/09/2020, South West- Cornwall & Plymouth Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK +442071048033/53, cornwallandplymouth.rec@hra.nhs.uk), ref: 20/SW/0124
2. Approved 11/03/2020, Children's Health Ireland at Crumlin Medical Research Committee (Crumlin, Dublin 12, Ireland; +353 (0) 14096243; no email provided), ref: Gen/807/20
3. Approved 30/06/2020, Children's Health Ireland at Temple Street ethics committee (Research Office, Temple Street Children’s University Hospital, Temple Street, Dublin 1, Ireland; +353 (0)1 892 1787, research@cuh.ie), ref: 20.020
4. Approved 17/08/2020, Children's Health Ireland at SJH/TUH Research Ethics Committee (Tallaght University Hospital, Dublin 24, Ireland; +353 (0)1-414 2199; researchethics@tuh.ie), ref: 2020-07
5. Approved 11/06/2020, University Hospital Limerick ethics (Research Ethics Committee, UL Hospitals Group, USE, Unit 2, Loughmore Avenue, Raheen Business Park, Limerick, V94P7X9, Ireland; +353 (0)61 482519; joanne.oconnor@hse.ie), ref: 055/2020
6. Approved 27/08/2020, St Vincent’s Healthcare Group Ethics and Medical Research Committee (Education and Research Centre, Elm Park, Dublin 4, Ireland; +353 (0)1-2214117; leona.malone@ucd.ie), ref: RS20-047

Study design

Multicenter observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Cystic fibrosis

Intervention

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 in RECOVER to gain important insight into how Kaftrio works, and what impact it has on rescue of CFTR function in this group of people.

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).

Subject participation is 27 months. Prior to any study assessments being complete, the participant will be contacted by a member of the study team provided information on the study in age-appropriate information leaflets, and request the participant to review. If the participant is happy to take part in the study, a team member will arrange a day for the participant to come to the clinical study site where the investigator will take informed consent. Once consent has been obtained, the participant will undergo several tests at -3 month visit and baseline prior to starting on commercially available Kaftrio (at the dosage decided by their clinician). Once the participant has started this triple combination modulator therapy, they will be monitored at 3 monthly intervals, which will coincide with the patients 3 monthly clinic visits.

Intervention type

Drug

Phase

Not Applicable

Drug names

Kaftrio (ivacaftor, tezacaftor, and elexacaftor)

Primary outcome measure

1. Lung clearance index (LCI or multiple breath washout) is measured to determine the effect of treatment on pulmonary function. It will be measured at -3 months, baseline, 6 months, 12 months, 18 months and 24 months
2. Spirometry controlled CT will assess the effect of triple combination modulator therapy (TCMT) on the CT scores. It is for patients on the advanced testing group only. It will be measured at baseline, 12 months and 24 months
3. Height/weight/BMI will be used for pulmonary function and to determine the effects of nutrition. It is measured at -3 months, baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
4. FEV1 (spirometry) is measured to determine the effect of treatment on pulmonary function. It is measured at -3 months, baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
5. Airway sampling (microbiology) will be used the measure the effect on TCMT on airway infection and inflammation in children and adults with CF. It will be measured at -3 months, baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months
6. Nasal lavage will be used to measure the effect of TCTM on airway infection and inflammation. It is measured on patients in the advanced testing arm only. This will be measured at baseline, 6 months and 12 months
7. FeNO (exhaled nitric oxide) is used to measure airway infection and inflammation. It is measured at -3 months, baseline, 6 months and 12 months
8. Liver function testing will be used to determine the effect of TCMT on nutrition, gastrointestinal symptoms, gut inflammation and pancreatic function in children and adults over a 2-year period. It is measured at baseline, 3 months, 6 months, 12 months and 24 months
9. Liver ultrasound will be used to determine TCMT on nutrition, gastrointestinal symptoms, gut inflammation and pancreatic function. It will be measured at baseline, 12 months and 24 months
10. Sputum sample collection is for the advanced testing group only. This will be used to determine TCMT effect on airway infection and inflammation. It will be measured at baseline, 6 months, 12 months and 24 months
11. Liver examination will be performed at baseline, 12 months and 24 months as part of the nutritional, gastrointestinal, gut inflammation and pancreatic function aim
12. Effect of TCMT on digestive tract by stool sample collection will be performed at baseline, 1 month, 6 months and 24 months as above
13. Blood sample collection will occur at baseline, 12 months and 24 months. The EDTA blood sample will be used for genetic modifiers of treatment response by our collaborators in Toronto
14. Abdominal symptom questionnaire and score will be used for nutritional and gastrointestinal symptoms outcomes. It is measured at -3 months, baseline, 1 month, 2 months, 6 months, 12 months and 24 months
15. CFQ-R questionnaire will be administered at baseline, 6 months, 12 months and 24 months. This has components on digestion, respiratory and quality of life
16. Pharmacy records (medication pick up rates) will be reviewed at baseline, 12 months and 24 months to assess the impact of the introduction of TCMT on antibiotic treatment of pulmonary disease and on adherence
17. Adherence and barriers to adherence questionnaires will be collected at - 3 months, baseline, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months. This will assess adherence impact with overall medical treatments for CF
18. MEMs caps reading will be at 12 months and will assess adherence to TCMT
19. Antibiotic use (through prescribed treatment plan and pharmacy pick up rates) will be measured at baseline, 12 months and 24 months, and will assess the impact of the introduction of TCMT on antibiotic treatment for pulmonary disease
20. Effect of TCMT on sweat, sweat chloride will be measured at baseline, 3 months, 12 months and 24 months

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/01/2020

Overall trial end date

30/06/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Children and adults with CF and starting on triple combination CFTR modulator treatment
2. Subjects must be taking the full dose of the triple combination compound.

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

237

Participant exclusion criteria

1. Patients not willing to comply with study procedures or assessments
2. Individuals on clinical trials of investigational CFTR modulators.

Recruitment start date

27/08/2020

Recruitment end date

30/03/2024

Locations

Countries of recruitment

Ireland, United Kingdom

Trial participating centre

Children's Health Ireland at Crumlin
Crumlin
Dublin
D12 N512
Ireland

Trial participating centre

Children's Health Ireland at Temple Street
Temple Street
Dublin
D01 YC67
Ireland

Trial participating centre

Children's Health Ireland at Tallaght
Tallaght
Dublin
D24 NR0A
Ireland

Trial participating centre

University Hospital Limerick
Children's Arc Butterfly ward St. Nessans Rd Dooradoyle
Limerick
V94 F858
Grenada

Trial participating centre

St. Vincent's University Hospital
Merrion Road
Dublin
D04 N2E0
Ireland

Trial participating centre

Royal Brompton Hospital
Sydney St Chelsea
London
SW3 6NP
United Kingdom

Trial participating centre

Belfast City Hospital
Lisburn Rd
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Royal Belfast Hospital for Sick Children
274 Grosvenor Rd
Belfast
BT12 6BA
United Kingdom

Sponsor information

Organisation

Royal College of Surgeons in Ireland

Sponsor details

123 St Stephen's Green
Saint Peter's
Dublin
D02 YN77
Ireland
+353 (0)1-8093863
sponsorship@rcsi.ie

Sponsor type

University/education

Website

https://www.rcsi.com/dublin

Funders

Funder type

Charity

Funder name

Cystic Fibrosis Foundation

Alternative name(s)

The Cystic Fibrosis Foundation, CF Foundation, The CF Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both public and private)

Location

United States of America

Funder name

Cystic Fibrosis Trust

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Cystic Fibrosis Ireland

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Dissemination will be a continuous process throughout the project as results are obtained, and dissemination channels reviewed annually to determine if an update is needed as new information comes to light. The Management Group will determine when an update is required. Our objectives are to disseminate results and project achievements to international stakeholders, thought-leaders, and equivalent institutions worldwide through structured dissemination activities. Given that most project results will be clinical/scientific in nature, we anticipate that the key audiences will be clinicians and researchers in industry and academia. These audiences will be reached via publicly accessible scientific publications (peer-reviewed high impact journals) and presentations at international conferences such as the North American Cystic Fibrosis Conference (NACFC) and European CF Conference. SciVal and Altmetrics (https://www.altmetric.com/) will be used to measure research impact, providing evidence of the broad reach and potential future impacts of research. Altmetric data will be reported (using Leiden Manifesto principles) to give an accurate indication of attention and engagement generated by individual outputs, which will be used to improve the reporting and dissemination of our research/. All collaborators will participate in dissemination, and funding for high-quality dissemination, and communications have been justified in the budget template, including publication costs, and conference registration fees.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

30/06/2024

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

03/11/2020: Trial’s existence confirmed by South West- Cornwall & Plymouth Research Ethics Committee.