VATS Surgery Compared to Drainage in the Treatment of Pleural Empyema

NCT04095676 | Recruiting DMC

• 1 other identifier: FIVERVATS1
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 3

Brief Summary

Pleura empyema is a frequent disease with a high morbidity and a mortality rate of approximately 15%. Pleura empyema is characterized by the passage of three stages (I - III). The aim of treating the disease is to remove the infection and provide fully expansion of the lung. The initial treatment at the early stage of the disease (stage I) is simple drainage. In clinical practice, stages II and III are treated alike. Current standard treatment for these stages is drainage with ultrasound (ULS) -guided pigtail. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of Video Assisted Thoracoscopic Surgery (VATS). The theoretical advantage of early surgery is that patients undergo rapid, definitive treatment. Furthermore, surgery can ensure optimal drain placement. How best to treat these patients (drainage or surgery) is still under clinical evaluation and depends to a great extent on local clinical practice. It is only to a limited extent based on scientific evidence. The aim of this study is to determine if there is a difference in outcome in patients diagnosed with stage II and stage III empyema who either receive primary VATS surgery or ULS guided drainage and intrapleural therapy (fibrinolytic (altaplasm) with DNase (Pulmozyne ®)) The primary outcome is Hospitalization time and secondary outcomes is e.g. mortality, health related costs and quality of life. The present study can thus provide new and highly relevant knowledge as well as change the treatment of these patients, both nationally and internationally. It is planned that a total of 184 patients will be included in the project. The study takes place as a collaboration between all four thoracic surgical departments and the major pulmonary medicine departments in Denmark. In addition, the study has international collaborators/consultants who will provide counselling in connection with the study.

Conditions

Pleural Empyema

Outcome Measures

Primary Outcomes (1)

• Length of hospital stay

  Admission time is defined as the time from first admission in the course of the hospitalization and to the completion of treatment defined as time of discharge from hospital without need of any additional invasive treatment.

  Through study completion, an average of 1 year

Secondary Outcomes (12)

• Length of hospital stay in subgroups

  Through study completion, an average of 1 year

• Length of hospital stay after commencement of intervention

  Through study completion, an average of 1 year

• Days at home up to 30 days after intervention (DAH30) treatment

  Through study completion, an average of 1 year

• 30-day and in-hospital mortality

  Through study completion, an average of 1 year

• Proportion of patients where primary intervention could be considered as definitive treatment

  30 days

Study Arms (2)

VATS / surgical group

EXPERIMENTAL

The VATS procedure must be completed as soon as possible and no later than 48 hours after randomisation. The surgery is performed with the patient in a 90 degree sideways position, using general anesthesia. Access is obtained through one to three ports, followed by purification and possibly decortication, and insertion of one pleural drain (sizes 24 - 32F) at the end of surgery. 20 ml Marcain is used as local analgetic and applied at the incision sites or as a nerve block. In the VATS group, suction on drain (- 15 cm H20) is applied in the first day after the procedure. Operator must have relevant training and competencies corresponding to the specialist level within the relevant specialty and be registered and approved by the steering committee.

Procedure: VATS group

Drain and intrapleural therapy group

ACTIVE COMPARATOR

Pigtail is applied as soon as possible and within 48 hours after randomisation. Drain placement is carried out using ULS. Operators (conductors of the procedure) must have relevant training and competencies corresponding to the specialist level within the relevant specialty and be approved by the steering committee to conduct the procedure. A pigtail catheter (minimum 10F) is inserted. Operator determines the size of drain and whether drain placement is done with one-step or Seldinger technic. The intrapleural therapy consists of treatment with the following two drugs: * intrapleural Actilyse® (alteplase) 10 mg twice daily for three days * intrapleural Pulmozyme® (DNase) 5 mg twice daily for three days

Procedure: Drain and intrapleural therapy group

Interventions

VATS group PROCEDURE

VATS procedure with drainage, including rinse with NaCl

VATS / surgical group

Drain and intrapleural therapy group PROCEDURE

Drainage with pigtail and Intrapleural therapy

Drain and intrapleural therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or more on the day of hospitalization
• Must be able to provide informed consent
• Acute hospitalization within the last 48 hours
• Meeting diagnostic criteria for community acquired pleural infection using the following criteria:
• A clinical presentation compatible with pleural infection AND
• Has pleural fluid which is either:
• purulent pleural fluid or
• gram stain positive or
• culture positive or
• acidic with pH \< 7.2 or
• low pleural fluid glucose (\< 2 mmol/L) in the absence of accurate pH measurement or
• septated pleural fluid on ultrasound

You may not qualify if:

• Breastfeeding
• Declared terminally ill or a predicted survival of less than 3 months
• Previous intrathoracic surgery (within \<1 year on the same side of the thorax as where the parapneumonic effusion/pleural empyema is located
• Previously (within \<1 year) hospitalized with with complex parapneumonic effusion (stage II) or pleural empyema (stage III)
• Drainage during the current admission on the same side of the thorax (excluding diagnostic pleural puncture)
• Hospitalization within 7 days prior to current hospitalization
• Previous allergic reaction to alteplase or DNase
• Use of alteplase therapy contraindicated:
• Ongoing treatment with oral anticoagulant incl. new oral anticoagulants (e.g. warfarin (Marevan), Dabigatranetexilat (Pradaxa), Rivaroxaban (Xarelto), Apixaban (Eliquis), Endoxaban (Lixiana))
• Significant ongoing bleeding or within last six months
• Known haemorrhagic diathesis
• Previous or suspected intracranial hemorrhage
• Suspected subarachnoidal hemorrhage or condition following subarachnoidal hemorrhage from aneurysm
• All forms of damage to the central nervous system (e.g. cerebral tumors, aneurysm, intracranial / spinal surgery)
• Recent (within 10 days) cardiac resuscitation, birth, or perforation of non-compressible blood vessel (e.g. puncture of v. subclavia, v. jugularis)

Sponsors & Collaborators

• Thomas Decker Christensen: lead
• Odense University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Aalborg University Hospital: collaborator

Study Sites (3)

Aarhus University Hospital

Aarhus, Aarhus, 8200, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

NOT YET RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Related Publications (15)

• Maskell NA, Davies CW, Nunn AJ, Hedley EL, Gleeson FV, Miller R, Gabe R, Rees GL, Peto TE, Woodhead MA, Lane DJ, Darbyshire JH, Davies RJ; First Multicenter Intrapleural Sepsis Trial (MIST1) Group. U.K. Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005 Mar 3;352(9):865-74. doi: 10.1056/NEJMoa042473.

  PMID: 15745977 BACKGROUND

• Davies HE, Davies RJ, Davies CW; BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug;65 Suppl 2:ii41-53. doi: 10.1136/thx.2010.137000. No abstract available.

  PMID: 20696693 BACKGROUND

• Molnar TF. Current surgical treatment of thoracic empyema in adults. Eur J Cardiothorac Surg. 2007 Sep;32(3):422-30. doi: 10.1016/j.ejcts.2007.05.028. Epub 2007 Jul 23.

  PMID: 17646107 BACKGROUND

• Tokuda Y, Matsushima D, Stein GH, Miyagi S. Intrapleural fibrinolytic agents for empyema and complicated parapneumonic effusions: a meta-analysis. Chest. 2006 Mar;129(3):783-90. doi: 10.1378/chest.129.3.783.

  PMID: 16537882 BACKGROUND

• Hooper CE, Edey AJ, Wallis A, Clive AO, Morley A, White P, Medford AR, Harvey JE, Darby M, Zahan-Evans N, Maskell NA. Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection. Eur Respir J. 2015 Aug;46(2):456-63. doi: 10.1183/09031936.00147214. Epub 2015 May 28.

  PMID: 26022948 BACKGROUND

• Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740.

  PMID: 21830966 BACKGROUND

• Scarci M, Abah U, Solli P, Page A, Waller D, van Schil P, Melfi F, Schmid RA, Athanassiadi K, Sousa Uva M, Cardillo G. EACTS expert consensus statement for surgical management of pleural empyema. Eur J Cardiothorac Surg. 2015 Nov;48(5):642-53. doi: 10.1093/ejcts/ezv272. Epub 2015 Aug 7.

  PMID: 26254467 BACKGROUND

• Bagheri R, Tavassoli A, Haghi SZ, Attaran D, Sadrizadeh A, Asnaashari A, Basiri R, Salehi M, Moghadam KA, Tabari A, Sheibani S. The role of thoracoscopic debridement in the treatment of parapneumonic empyema. Asian Cardiovasc Thorac Ann. 2013 Aug;21(4):443-6. doi: 10.1177/0218492312466858. Epub 2013 Jul 11.

  PMID: 24570527 BACKGROUND

• Redden MD, Chin TY, van Driel ML. Surgical versus non-surgical management for pleural empyema. Cochrane Database Syst Rev. 2017 Mar 17;3(3):CD010651. doi: 10.1002/14651858.CD010651.pub2.

  PMID: 28304084 BACKGROUND

• Koppurapu V, Meena N. A review of the management of complex para-pneumonic effusion in adults. J Thorac Dis. 2017 Jul;9(7):2135-2141. doi: 10.21037/jtd.2017.06.21.

  PMID: 28840015 BACKGROUND

• Bishay M, Short M, Shah K, Nagraj S, Arul S, Parikh D, Jawaheer G. Efficacy of video-assisted thoracoscopic surgery in managing childhood empyema: a large single-centre study. J Pediatr Surg. 2009 Feb;44(2):337-42. doi: 10.1016/j.jpedsurg.2008.10.083.

  PMID: 19231530 BACKGROUND

• Ravn, J. Should all patients with pleural emphyema be referred to a thoracic operation? Dan. Med. J. 179, V69273 (2017).

  BACKGROUND

• Psallidas I, Yousuf A, Talwar A, Hallifax RJ, Mishra EK, Corcoran JP, Ali N, Rahman NM. Assessment of patient-reported outcome measures in pleural interventions. BMJ Open Respir Res. 2017 Jul 3;4(1):e000171. doi: 10.1136/bmjresp-2016-000171. eCollection 2017.

  PMID: 28883922 BACKGROUND

• Rahman NM, Kahan BC, Miller RF, Gleeson FV, Nunn AJ, Maskell NA. A clinical score (RAPID) to identify those at risk for poor outcome at presentation in patients with pleural infection. Chest. 2014 Apr;145(4):848-855. doi: 10.1378/chest.13-1558.

  PMID: 24264558 BACKGROUND

• Christensen TD, Bendixen M, Skaarup SH, Jensen JU, Petersen RH, Christensen M, Licht P, Neckelmann K, Bibby BM, Moller LB, Bodtger U, Borg MH, Saghir Z, Langfeldt S, Harders SMW, Bedawi EO, Naidu B, Rahman N, Laursen CB. 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 Mar 9;12(3):e054236. doi: 10.1136/bmjopen-2021-054236.

  PMID: 35264347 DERIVED

MeSH Terms

Conditions

Empyema, Pleural

Interventions

Drainage

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Empyema; Suppuration; Pleural Diseases; Respiratory Tract Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Surgical Procedures, Operative

Study Officials

• Christian B Laursen, MD, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Christian B Laursen, MD, PhD

  Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas D Christensen, MD, PhD

CONTACT

24778857; tdc@clin.au.dk

Morten Bendixen, MD, PhD

CONTACT

24778895; pinseferie@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant, Professor, MD, DMSc., Ph.D

Model Details: * Randomized, controlled study * Not blinded (open label) * National multicenter study

Study Record Dates

• First Submitted: September 5, 2019
• First Posted: September 19, 2019
• Study Start: October 30, 2022
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2028
• Last Updated: October 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After completion of the study - after / during the publication process
• Access Criteria: Mail to the principle investigator

Locations

DK (3)