Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 15;12(1):2502237.
doi: 10.1080/20018525.2025.2502237. eCollection 2025.

Conducting a registry-based randomised trial (REDOX) in chronic respiratory failure: experiences and advice

Josefin Sundh  1 , Magnus Ekström  2
Affiliations
Review

Conducting a registry-based randomised trial (REDOX) in chronic respiratory failure: experiences and advice

Josefin Sundh et al. Eur Clin Respir J. .

Abstract

Registry-based randomised controlled trials (R-RCTs) represent a paradigm shift in research, with the potential to accomplish pragmatic but large trials with high external validity. In this paper, we review our experiences from planning and performing the REgistry-based randomised controlled trial of treatment Duration and mortality in long-term OXygen therapy (REDOX) trial, the first R-RCT within respiratory medicine. The REDOX study compared the two established treatment options of home oxygen 15 and 24 h per day. Previous recommendations to use oxygen for at least 15 h but preferably 24 h per day were based on a non-randomised comparison of two different studies. We hypothesised that oxygen 24 h/day was non-superior to 15 h/day and used the Swedish National Registry for Respiratory Failure (Swedevox) to perform an R-RCT showing that home oxygen 24 h/day does not improve survival, hospitalisation or patient-reported outcomes within 1 year. We describe the entire procedure of REDOX from planning to publication and use it to discuss challenges and potential solutions for future R-RCTs. In summary, common features of R-RCTs are the use of a registry for identification and randomisation of participants and for reporting and collecting baseline and outcome data, and the design is typically used to compare two treatment options. Important strengths are high generalisability, low cost, feasibility for consecutive recruitment in clinical practice, and high completeness of follow-up. Limitations include that coverage, completeness and accuracy of baseline data may differ between registries. Specific challenges (and solutions) in REDOX were addressing an important question (pragmatic clinical trials), management (clinical research support teams), costs (using registry-based infrastructure), different electronic data capture systems (posttrial linkage), slow recruitment (amendment of protocol) and resistance to challenge treatment traditions.

Keywords: hospitalisation; hypoxemia; mortality; oxygen therapy; trial design.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Final design of the REDOX trial.
Figure 2.
Figure 2.
Time line for conducting the REDOX trial. The blue arrow depicts the time period of recruitment.
Figure 3.
Figure 3.
Recruitment over time by study centre in the REDOX trial.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Nocturnal Oxygen Therapy Trial Group . Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980;93(3):391–8. doi: 10.7326/0003-4819-93-3-391 - DOI - PubMed
    1. Medical Research Council Working Party . Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981;317(8222):681–686. doi: 10.1016/S0140-6736(81)91970-X - DOI - PubMed
    1. Anthonisen NR. Prognosis in chronic obstructive pulmonary disease: results from multicenter clinical trials. Am Rev Respir Dis. 1989;140(3_pt_2):S95–99. doi: 10.1164/ajrccm/140.3_Pt_2.S95 - DOI - PubMed
    1. Ahmadi Z, Sundh J, Bornefalk-Hermansson A, et al. Long-term oxygen therapy 24 vs 15 h/day and mortality in chronic obstructive pulmonary disease. PLOS ONE. 2016;11(9):e0163293. doi: 10.1371/journal.pone.0163293 - DOI - PMC - PubMed
    1. Björklund F, Ekström M. Adverse effects, smoking, alcohol consumption, and quality of life during long-term oxygen therapy: a nationwide study. Ann Am Thorac Soc. 2022;19(10):1677–1686. doi: 10.1513/AnnalsATS.202110-1174OC - DOI - PMC - PubMed

LinkOut - more resources