Cystic fibrosis (CF) is a genetic condition of impaired membrane electrolyte transport and is characterised by defects in the production and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Ground-breaking CFTR modulator therapy has resulted in a notable shift in the clinical presentation and progressive nature of CF, across both pulmonary and extrapulmonary systems. Access to CFTR modulator therapies in people with CF is occurring in a staged, descending age process, with clinical trials focusing primarily on safety and efficacy. There is a lack of robust, real-world longitudinal data on CFTR modulator therapy in infants and young children where extrapulmonary outcomes such as growth, micronutrient status and pancreatic function are the key focus.

Pancreatic, nutritional and clinical outcomes in children 0–5 years with CF during the first 2 years of CFTR modulator therapy (PaNC) is a prospective cohort study involving all eight tertiary paediatric CF centres in Australia. Infants and children 4 months to 5 years of age who are eligible for elexacaftor/tezacaftor/ivacaftor (ETI) or ivacaftor (IVA) meet the inclusion criteria for PaNC, with a total eligible cohort of 303 children at the commencement of recruitment. The primary outcomes are change in weight-for-length/body mass index z score and change in serum micronutrient status, at 6–12 monthly intervals, during the first 2 years of treatment with ETI or IVA. Secondary outcomes include change in exocrine pancreatic function, measured by faecal elastase-1, change in the use and dose of pancreatic enzyme replacement therapy, nutritional and gastrointestinal therapies and change in sweat chloride levels. Linear mixed modelling will be used to analyse primary and secondary endpoints. This protocol is reported in accordance with ‘The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement’ reporting guidelines.

Overarching governance and ethics approval has been granted by Monash Health Human Research Ethics Committee, in addition to all eight sites receiving site-specific authorisation approvals prior to the commencement of recruitment. Opportunities for CF consumers to be involved in targeted dissemination plans will be initiated via CF Australia at the completion of the study period. Additionally, a summary of non-identifiable results will be provided to CF consumers and CF healthcare providers via scientific and lay conferences and via peer-reviewed journals.

ACTRN12624001185550; Pre-results.

Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. It is comprised of deep vein thrombosis (DVT) and pulmonary embolism and can be potentially life-threatening. Patients undergoing surgery are at increased risk of developing VTE within hospital admission and 90 days after hospital discharge are collectively known as hospital-acquired thrombosis (HAT). Without the use of thromboprophylaxis, the untreated risk of VTE is reported to be as high as 40–60% in those undergoing major orthopaedic procedures and around 15–40% in the general surgical population.

HAT accounts for around 12 000 deaths per year in the UK. For patients undergoing surgery, there is good evidence for the use of thromboprophylaxis to prevent VTE.

Thromboprophylaxis is available in both pharmacological and mechanical forms. While there is a huge body of evidence demonstrating that pharmacological thromboprophylaxis significantly reduces VTE by 30–65%, the benefit of graduated compression stockings (GCS) has been called into question. The GRACE study (Graduated Compression stocking as an adjunct to Extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention) aims to evaluate the adjuvant benefit of GCS in addition to extended duration pharmacological thromboprophylaxis (EDPTP) for elective surgical patients at highest risk of VTE.

GRACE is a pragmatic, multicentre randomised trial of adults undergoing surgery who are at high risk of VTE. Participants are randomised into a 1:1 ratio to either EDPTP and compression stockings (control arm) or EDPTP (intervention arm). Following randomisation, participants will undergo surgery and be followed up centrally at 7, 21–35 and 90 days after their procedure. All participants will be offered a bilateral full lower limb duplex scan at 21–35 days post procedure to capture any asymptomatic DVT.

The trial aims to randomise 8608 participants from around 50 National Health Service (NHS) and non-NHS sites in the UK over a 24-month period. The primary endpoint is any imaging-confirmed incidence of VTE within 90 days of surgery.

On 20 December 2023, GRACE received favourable ethical approval from the Wales Research Ethics Committee 3 Cardiff (23/WA/0350) and the Health Research Authority (IRAS 333539). The results of the study will be disseminated via peer-reviewed publications, presentation at national and international conferences and to study participants via electronic newsletter and social media channels.

ISRCTN11667770.