Title: A randomised open label trial to assess change in respiratory function for people with cystic fibrosis (pwCF) established on triple combination therapy (Kaftrio™) after rationalisation of nebulised muco-active therapies (the CF STORM trial)
Funder: Department of Health and Social Care

Abstract: Cystic Fibrosis (CF) affects over 10,000 people in the UK and the average age at death for a person in the UK with CF is 31 years. For people with CF and their healthcare teams, the top priority for research has been identified as simplifying the burden associated with treatment. People with CF spend many hours every day on multiple treatments, including aerosolised therapies delivered by nebulisers to keep their lungs stable and prevent chest infections._x000D_ _x000D_ The CF STORM trial has been designed to address the question of how to safely reduce treatment burden. The imminent introduction in the UK of a highly effective new drug (Kaftrio™) which is suitable for the majority of people with CF makes CF STORM a particularly timely study. Trials have shown that Kaftrio™ therapy is transformative for people with CF who have one or two copies of the F508del variant (~70% of the UK CF population). Introduction of Kaftrio™ therapy provides an ideal opportunity to robustly explore reduction in treatment burden in a clinical trial. _x000D_ _x000D_ The design of the CF STORM study has been driven by people with CF and their families._x000D_ _x000D_ Participants in CF STORM who are stable on triple therapy (Kaftrio™) will be randomly selected to either continue with their standard treatment regimen or reduce their treatment burden by removing nebulised drugs that are designed to break down the sticky mucus in their airways (called muco-active therapies). These therapies include dornase alfa (e.g., Pulmozyme™) and hypertonic saline (e.g., Nebusal™). After 12 months we will compare the change in respiratory function for participants still on nebulised muco-active therapies to those who have stopped. In addition, other outcomes that are important to people with CF will be measured, including the number of new chest infections, quality of life and need for extra treatments. All these outcomes will be collected at standard clinic visits and recorded on the national CF Registry. Participants in this study will not require any extra study visits to the hospital. If hospital appointments are not possible because of the COVID-19 pandemic, we will collect data from remote consultations and home spirometry measurements._x000D_ _x000D_ The study will enrol 764 people with CF across the UK and will enable us to determine whether stopping nebulised muco-active treatments for pwCF on triple therapy can be confidently recommended with the knowledge that it will not result in a significant reduction in respiratory function._x000D_ _x000D_ As transformative therapies emerge for CF and other conditions it is important we evaluate rigorously the impact on the patient journey. CF STORM presents an innovative registry-based approach to achieve this and provide a framework for future stopping studies.

Lay abstract: CF STORM will be a non-inferiority randomised open-label trial, undertaken on a national patient registry, to evaluate whether people with CF (pwCF) can rationalise their daily treatment without a significant reduction in their respiratory function. Patients established on triple therapy, elexacaftor-tezacaftor-ivacaftor (E-T-I), for more than three months will be enrolled and randomly allocated to either stop or continue their nebulised muco-active treatment (dornase alfa, hypertonic saline or both). The primary outcome will be change in percent predicted Forced Expiratory Volume in One Second (ppFEV1) at 12 months. This and other secondary outcomes (including need for extra antibiotic treatment, quality of life (QoL), and weight) will be collected on the national UK Cystic Fibrosis (CF) Registry. In addition, eligibility will be assessed, eConsent recorded, and randomisation will be undertaken on the registry. This provides opportunity for pwCF to be recruited remotely, in line with delivery of care during the COVID-19 pandemic. The results from the CF STORM trial, together with data from the SIMPLIFY trial (a shorter non-pragmatic trial being undertaken in the US) will inform the knowledge transfer exercise that will be undertaken by the CF STORM team at the end of the trial, co-ordinated by the PPI leads.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CONGENITAL DISORDERS