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Trials
Published in: Trials 1/2023

Open Access 01-12-2023 | Cystic Fibrosis | Study protocol

BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis

Authors: Andre Schultz, Charlie McLeod, Scott Berry, Julie Marsh, Anne McKenzie, Mitch Messer, Jamie Wood, Ben Saville, Adam Jaffe, Sarath Ranganathan, Steve Stick, Peter Wark, Steve Webb, Tom Snelling

Published in: Trials | Issue 1/2023

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Abstract

Background

Cystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results.

Methods

This platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV1) from the commencement of intensive therapy to 7 to 10 days afterwards.

Discussion

The BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately.

Trial registration

ANZCTR BEAT CF Platform – ACTRN12621000638831. Registration date: Sept. 26, 2022.
Appendix
Available only for authorised users
Literature
1.
Sanders DB, Solomon GM, Beckett VV, West NE, Daines CL, Heltshe SL, et al. Standardized Treatment of Pulmonary Exacerbations (STOP) study: observations at the initiation of intravenous antibiotics for cystic fibrosis pulmonary exacerbations. J Cyst Fibros. 2017;16(5):592–9.CrossRefPubMedPubMedCentral
2.
3.
4.
5.
Smith AL, Doershuk C, Goldmann D, Gore E, Hilman B, Marks M, et al. Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis. J Pediatr. 1999;134(4):413–21.CrossRefPubMed
6.
Smith S, Rowbotham NJ, Charbek E. Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Cochrane Database Syst Rev. 2018;10:CD008319.PubMed
7.
Rowbotham NJ, Smith S, Leighton PA, Rayner OC, Gathercole K, Elliott ZC, et al. The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers. Thorax. 2018;73(4):388–90.CrossRefPubMed
8.
Moher DD, Glasziou PF, Chalmers ID, Nasser MDDS, Bossuyt PMMP, Korevaar DAMD, et al. Increasing value and reducing waste in biomedical research: who's listening? Lancet (British edition). 2016;387(10027):1573–86.
9.
Angus DC, Alexander BM, Berry S, Buxton M, Lewis R, Paoloni M, et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797–807.CrossRef
10.
11.
Goss CH, Edwards TC, Ramsey BW, Aitken ML, Patrick DL. Patient-reported respiratory symptoms in cystic fibrosis. J Cyst Fibros. 2009;8(4):245–52.CrossRefPubMed
12.
Quittner AL, Buu A, Messer MA, Modi AC, Watrous M. Development and validation of the cystic fibrosis questionnaire in the United States: a health-related quality-of-life measure for cystic fibrosis. Chest. 2005;128(4):2347–54.CrossRefPubMed
13.
McLeod C, Wood J, Schultz A, Norman R, Smith S, Blyth CC, et al. Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review. J Cyst Fibros. 2020;19(6):858–67.CrossRefPubMed
14.
Currie G, Tai A, Snelling T, Schultz A. Variation in treatment preferences of pulmonary exacerbations among Australian and New Zealand cystic fibrosis physicians. BMJ Open. Respir Res. 2021;8(1).
15.
West N, Goss C, Heltshe S, Skalland M, Sanders D, Jain R, et al. WS09.6 A randomised clinical trial of antimicrobial duration for treatment of cystic fibrosis pulmonary exacerbations (STOP2). J Cyst Fibros. 2021;20:S18.CrossRef
16.
Heltshe SL, Goss CH, Thompson V, Sagel SD, Sanders DB, Marshall BC, et al. Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis. Thorax. 2016;71(3):223–9.CrossRefPubMed
17.
Goss CH, Heltshe SL, West NE, Skalland M, Sanders DB, Jain R, et al. A randomized clinical trial of antimicrobial duration for cystic fibrosis pulmonary exacerbation treatment. Am J Respir Crit Care Med. 2021;204(11):1295–305.CrossRefPubMedPubMedCentral
18.
VanDevanter DR, Heltshe SL, Spahr J, Beckett VV, Daines CL, Dasenbrook EC, et al. Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis. J Cyst Fibros. 2017;16(5):607–15.CrossRefPubMedPubMedCentral
19.
Stick S, Tiddens H, Aurora P, Gustafsson P, Ranganathan S, Robinson P, et al. Early intervention studies in infants and preschool children with cystic fibrosis: are we ready? Eur Respir J. 2013;42(2):527–38.CrossRefPubMed
20.
Simpson SJ, Mott LS, Esther CR Jr, Stick SM, Hall GL. Novel end points for clinical trials in young children with cystic fibrosis. Expert Rev Respir Med. 2013;7(3):231–43.CrossRefPubMedPubMedCentral
21.
Kent L, Reix P, Innes JA, Zielen S, Le Bourgeois M, Braggion C, et al. Lung clearance index: evidence for use in clinical trials in cystic fibrosis. J Cyst Fibros. 2014;13(2):123–38.CrossRefPubMed
22.
Loeve M, Krestin GP, Rosenfeld M, de Bruijne M, Stick SM, Tiddens HA. Chest computed tomography: a validated surrogate endpoint of cystic fibrosis lung disease? Eur Respir J. 2013;42(3):844–57.CrossRefPubMed
23.
Waters V, Ratjen F. Pulmonary exacerbations in children with cystic fibrosis. Ann Am Thorac Soc. 2015;12(Suppl 2):S200–S6.CrossRefPubMed
24.
U.S Department of Health and Human Services, Food and Dug Administration, Centre for Drug Evaluton and Research (CDER), Center for Biologics Evaluation and Research (CBER). E9 (R1) addenum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. 2021. Microsoft Word - 32470419fnl E9 (R1) Statistical Principles for Clinical Trials Addendum Estimands and Sensitivity Analysis in (fda.​gov). Accessed 25 Aug 2022.
25.
Woodcock J, LaVange LM. Master protocols to study multiple therapies, multiple diseases, or both. New England J Med. 2017;377(1):62–70.CrossRef
26.
U.S Department of Health and Human Services, Food and Drug Administration, Centre for Drug Evaluton and Research (CDER), Center for Biologics Evaluation and Research (CBER), Oncology Center for Excellence (OCE). Master Protocols: efficient clinical trial design strategies to expedite development of oncology drugs and biologics: guidance for Industry. 2022. https://​www.​fda.​gov/​media/​120721. Accessed 20 Aug 2022.
27.
Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, et al. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) study. Rationale and design. Ann Am Thorac Soc. 2020;17(7):879–91.CrossRefPubMedPubMedCentral
28.
Karanatsios B, Prang K-H, Verbunt E, Yeung JM, Kelaher M, Gibbs P. Defining key design elements of registry-based randomised controlled trials: a scoping review. Trials. 2020;21(1):552.CrossRefPubMedPubMedCentral
29.
Ioannidis JPA, Adami H-O. Nested randomized trials in large cohorts and biobanks: studying the health effects of lifestyle factors. Epidemiology (Cambridge, Mass). 2008;19(1):75–82.CrossRefPubMed
30.
Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krle A-Jerić K, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica. 2015;38(6):506–14 English. PMID: 27440100; PMCID: PMC5114122.PubMed
Metadata
Title
BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis
Authors
Andre Schultz
Charlie McLeod
Scott Berry
Julie Marsh
Anne McKenzie
Mitch Messer
Jamie Wood
Ben Saville
Adam Jaffe
Sarath Ranganathan
Steve Stick
Peter Wark
Steve Webb
Tom Snelling
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07076-8

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