Administrative information
Title {1} | BEAT CF pulmonary exacerbations core protocol for evaluating management of pulmonary exacerbations in people with cystic fibrosis. |
Trial registration {2a and 2b}. | ANZCTR BEAT CF Platform – ACTRN12621000638831 accessible here. |
Protocol version {3} | Version 7. 8th November 2021. |
Funding {4} | Funding is provided by a Medical Research Future Fund Lifting Clinical Trials and Registries Capacity Grant (GNT1152376). |
Author details {5a} | A/Prof André Schultz Dr Charlie McLeod Dr Scott Berry Dr Julie Marsh Ms Anne McKenzie Mr Mitch Messer Jamie Wood Dr Ben Saville Prof Adam Jaffe Prof Sarath Ranganathan Prof Stephen Stick Prof Peter Wark Prof Steve Webb Prof Tom Snelling |
Name and contact information for the trial sponsor {5b} | University of Sydney, New South Wales, Australia, 2006 P: +61 2 8627 9280 |
Role of sponsor {5c} | As Sponsor, the University of Sydney assumes ultimate responsibility for the initiation, conduct, management, quality and integrity of data and financing, including for any nested studies. Other activities, including but not limited to design, conduct, safety monitoring, and reporting, are delegated to the Steering Committee. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Participant timeline {13}
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Category | Variable | Timing | Justification | |
---|---|---|---|---|
At cohort entry | 3-monthly | |||
Demographic data | Date of birth | Y | Age is independently associated with baseline lung function in CF. There may be “cohort” effects whereby those born in more recent periods have better outcomes because of improvements in care | |
Sex | Y | Sex is independently associated with lung function in CF | ||
Clinical | Genotype | Y | Validation of CF diagnosis | |
Sweat test results | Y | Validation of CF diagnosis | ||
Pancreatic exocrine status | Y | Y | Pancreatic function is independently associated with lung function in CF | |
CF-related diabetes | Y | Y | Diabetes is independently associated with lung function in CF | |
Known drug allergies or contraindications | Y | Y | Drug allergies and contraindications constrain therapeutic options, and plausibly confounds or modifies treatment effects | |
Concomitant medications | Y | Y | Use of concomitant medications plausibly confounds or modifies treatment effects, including toxicities | |
Laboratory | Total IgE | Ya | Y | Marker for allergic bronchopulmonary aspergillosis which is a cause of clinical deterioration and may confound PEx management |
Aspergillus-specific RAST | Ya | Y | Marker for allergic bronchopulmonary aspergillosis which is a cause of clinical deterioration and may confound PEx management | |
Date and details of any new, documented infection, or airway colonization | Ya | Y | The presence of specific pathogens may influence therapeutic choices, plausibly confounds or modifies treatment effects. Selection of resistant pathogens may be an untoward outcome of antibiotic therapy | |
Date and details of any new, documented infection with Clostridium difficile | Ya | Y | Clostridium difficile-related diarrhea is an important untoward outcome of antibiotic therapy | |
Patient-reported outcomes: | Cystic Fibrosis Questionnaire-revised (CFQ-R) for all participants ≥6 years old | Y | Y | Treatment of PEx plausibly impacts on quality-of-life (QoL) over time |
Anthropometric | Height | Y | Y | Height is associated with FEV1 and is essential for estimating the ppFEV1 |
Weight | Y | Y | Treatment of PEx plausibly impacts on weight over time | |
Spirometry | FEV1 | Yb | Y | Treatment of PEx plausibly impacts on lung function. The ppFEV1, is strongly associated with morbidity and mortality in CF |
Variable | Timing | Reason | |
---|---|---|---|
PEx therapy | Date and time of commencing IV therapy | Day 0 | As a time reference point for analyses |
PEx therapy | Location (hospital or HITH) | Daily | For description of the cohort. Location may constrain therapeutic options and plausibly confound or modify treatment effects |
Spirometry | FEV1 | Days 0 (at admission), 7, 14, 30, 60, and 180 | Treatment of PEx plausibly impacts on lung function, measured as ppFEV1; this is strongly associated with morbidity and mortality in CF |
Clinical assessment | Presence and quality of cough | Daily | Reduction in cough and/or improvement in cough quality are measures of successful treatment of PEx |
Presence of crepitations | Daily | Reduction in crepitations is a measure of successful treatment of PEx | |
Patient-reported outcomes | CRISS score (if > 12 years at admission) | Day 0: as close as practicable to the initiation of IV antibiotics, and not > 72 h afterwards, then days 7, 14, and 30 | CRISS is a validated measure of CF-related symptoms in the preceding 24 h. It is expected that successful treatment will result in an improved CRISS score. It will be used to assess clinical response to treatment for PEx |