Randomized controlled trial.

Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS) - guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of Video Assisted Thoracoscopic Surgery (VATS) as first line treatment.

The study is a national, multicentre randomized, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either 1) VATS procedure with drainage or 2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include e.g. mortality, need for additional interventions, consumption of analgesia and quality of life.

All patients provide informed consent before randomization. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www.clinicaltrials.gov, and monitored by the regional Good Clinical Practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences.

The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme®)) as first line treatment.

• TD Christensen, M Bendixen
  Department of Cardiothoracic and Vascular Surgery & Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
• RH Petersen
  Department of Cardio-thoracic Surgery, Rigshospitalet, Copenhagen University Hospital
• PB Licht
  Department of Cardiothoracic and Vascular Surgery, Odense University Hospital
• LB Møller
  Department of Cardiothoracic Surgery, Aalborg University University Hospital
• CB Laursen
  Department of Respiratory Medicine, Odense University Hospital
• SH Skaarup
  Department of Respiratory Medicine, Aarhus University Hospital
• JUS Jensen
  Department of Respiratory Medicine, Herlev-Gentofte Hospital, Copenhagen University Hospital
• BM Bibby
  Biostatistical Advisory Service (BIAS), Faculty of Health Sciences, Aarhus Universit

• NM Rahman, EO Bedawi
  NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
• B Naidu
  Department of Thoracic Surgery, Queen Elizabeth Hospital Birmingham, UK & Institute of Inflammation and Ageing, University of Birmingham, UK

• J Davidsen
  Department of Respiratory Medicine, Odense University Hospital
• M Stenger
  Department of Cardiothoracic and Vascular Surgery, Odense University Hospital

• Department of Cardio-thoracic Surgery, Rigshospitalet, Copenhagen University Hospital
• Department of Cardiothoracic and Vascular Surgery, Odense University Hospital
• Department of Cardiothoracic Surgery, Aalborg University Hospital
• Department of Respiratory Medicine, Odense University Hospital
• Department of Respiratory Medicine, Aarhus University Hospital
• Department of Respiratory Medicine, Herlev-Gentofte Hospital, Copenhagen University Hospital
• Department of Respiratory Medicine, Aalborg University Hospital
• Department of Respiratory Medicine, Holstebro Hospital
• Department of Respiratory Medicine, Viborg-Skive Hospital
• Department of Respiratory Medicine, Horsens Hospital
• Department of Respiratory Medicine, Randers Hospital
• Department of Respiratory Medicine, Lillebaelt Hospital, Kolding
• Department of Acute Medicine, Aabenrå Hospital
• Department of Respiratory Medicine, Esbjerg Hospital
• Department of Respiratory Medicine, Naestved-Slagelse Hospital
• Department of Acute Medicine, Odense University Hospital
• Department of Radiology, Aarhus University Hospital
• Department of Radiology, Odense University Hospital

This work was supported by the Novo Nordisk Foundation (grant no.: 0065455) and Skibsreder Per Henriksen, R. og Hustrus Fond.

• Christensen T. D., Bendixen M., Skaarup S. H., Jensen J., Petersen R. H., Christensen M., Licht P., Neckelmann K., Bibby B. M., Møller L. B., Bodtger U., Borg M. H., Saghir Z., Langfeldt S., Harders S. M. W., Bedawi E. O., Naidu B., Rahman N., Laursen C. B. (2022). Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment. BMJ Open. 2022;9;12(3):e054236. DOI: 10.1136/bmjopen-2021-054236.
• Christensen, T. D., Vad, H., Pedersen, S., Hvas, A-M., Wotton, R., Naidu, B. & Larsen, T. B. Venous Thromboembolism in Patients Undergoing Operations for Lung Cancer: A Systematic Review. Annals of Thoracic Surgery. 2013. DOI: doi.org/10.1016/j.athoracsur.2013.10.074.