Clinical trial NCT02359175: Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study
Official title: Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lung Neoplasms
Pain
Immune Suppression
Keywords: Pain
Pain Measurement
VAS
Visual Analog Pain Scale
Analgesics
Opioid
Epidural analgesia
VATS
Video-assisted Thoracic Surgery
Lobectomy
Wedge Resection
Segmental Resection
Cytokins
Immune cells
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2015-02-09
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Whereas it, in the case of conventional thoracotomy, has been demonstrated that thoracic epidural analgesia is more effective than systemic opioids in terms of pain relief and preservation of postoperative pulmonary function, the efficacy of epidural analgesia in video-assisted thoracic surgical (VATS) procedures, has not been sufficiently studied, but a beneficial effect might very well be present.

On the other hand, the risks associated with placement of a thoracic epidural catheter are well known and if similar pain relief can be achieved without it with no or only insignificant alternative side effects, this would be preferable.

The literature regarding the usefulness of epidural analgesia for reducing pain in Video-Assisted Thoracic Surgery is, at best, scarce with two small studies showing some effect and two showing no difference, none of the studies being blinded randomized controlled trials of adequate size.

The SEAVATS Study will try to answer this question.

Detailed description: Study plan:

The hypothesis is that there is no difference in the amount of pain the patients will experience after VATS for pulmonary neoplasms.

Study design and setting:

The project is designed as a prospectively, double blinded, randomized, placebo controlled study comparing pain in two groups of patients.

Both groups of patients will:

* Have a epidural catheter placed.
* Receive a basis level of analgesics consisting of paracetamol and a nonsteroidal anti- inflammatory drug combined with a nerveblock placed intercostally during surgery.
* Have access to i.v. opioids as needed for any experienced pain after surgery.

One group of patients will be given local anaesthetics through the epidural catheter supplemented with placebo medication orally while the other group will receive saline in the epidural catheter supplemented with opioids orally.

Data collection:

Data will, during hospitalization, be collected in the operating theatre, in the postoperative care unit and in the surgical ward. Six months after surgery a questionnaire will be send to the patients to do follow-up regarding residual sequelae after surgery and placement of epidural catheter. Further follow-up with questionnaire has been planned for subsequent years.

As a secondary objective, in fifty-six of the patients from The SEAVATS Study, blood samples will be gathered during surgery and one hour and 24 hours after surgery, and compared with pre-operative levels.

These blood samples will be analysed for immune cells (NK-cells, levels and activity) and cytokines (IL-6, IL-10, IL-12 and IFN-gamma) as indicators of immunological response to surgery.

Research ethics:

The project has obtained ethics approval from The Regional Scientific Ethical Committees for Southern Denmark and acceptance to perform clinical research has been granted by The Danish Health and Medicines Authority. Consent to data collection has been provided by The Danish Data Protection Agency. Before entering the project, consent will be obtained from all patients. Rigorous data security will be maintained for five years and afterwards all data will be deleted. The Study is registered with The European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) with EudraCT number 2014-000760-18 and is monitored by The Good Clinical Practice unit for Southern Denmark.

Eligibility criteria: Inclusion Criteria:

* Planned elective VATS lobectomy, wedge- or segmental resection. (for the subsequent biomarker study, only lobectomy is a inclusion criteria, specified in protocol amendment July 27th 2016)
* Patient has accepted to have epidural analgesia as part of the anaesthesia for the procedure.
* Informed consent is attained.
* Patient is over 18 years of age.
* Patient is mentally able to answer questionnaires included in the study.

Exclusion Criteria:

* Allergies to any of the medications used in the trial.
* History of previous peptic ulcer.
* History of chronic pain to any degree that will interfere with quantification of pain postoperatively.
* Dementia or reduced mental capacity to any degree that will interfere with quantification of pain postoperatively.
* Pregnancy.
* Contra-indications to placement of epidural catheter.
* Any concurrent cancer disease or use of immune modulating drugs (criteria added as part of a protocol amendment July 27th 2016 for a subsequent biomarkers study)

Primary outcomes:
measure: Intensity of pain (Self reported pain intensity)
timeFrame: 0-4 days
measure: Consumption "Rescue Analgesia" - i.v. opioids
timeFrame: 0-4 days
Secondary outcomes:
measure: Duration of surgery
timeFrame: 0-4 days
measure: Length of hospital stay
timeFrame: 0-4 days
measure: Time used placing epidural catheter
timeFrame: 0-4 days
measure: Side effects of epidural analgesia
timeFrame: 0-4 days
measure: Sequelae following VATS and placement of epidural catheter
timeFrame: 60 months
Other outcomes:
measure: Immune cells - NK cell levels.
timeFrame: During surgery and one hour and 24 hours after surgery, and compared with pre-operative levels.
measure: Immune cells - NK cell activity.
timeFrame: During surgery and one hour and 24 hours after surgery, and compared with pre-operative levels.
measure: Cytokines
timeFrame: During surgery and one hour and 24 hours after surgery, and compared with pre-operative levels.
measure: Survival after VATS
timeFrame: 60 months
Locations:
city: Odense C
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Department of Anaesthesia and Intensive Care - Odense University Hospital
name: Jimmy H Holm, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Richardson J, Cheema S. Thoracic paravertebral nerve block. Br J Anaesth. 2006 Apr;96(4):537. doi: 10.1093/bja/ael038. No abstract available.
citation: Kim JA, Kim TH, Yang M, Gwak MS, Kim GS, Kim MJ, Cho HS, Sim WS. Is intravenous patient controlled analgesia enough for pain control in patients who underwent thoracoscopy? J Korean Med Sci. 2009 Oct;24(5):930-5. doi: 10.3346/jkms.2009.24.5.930. Epub 2009 Sep 23.
citation: Freise H, Van Aken HK. Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth. 2011 Dec;107(6):859-68. doi: 10.1093/bja/aer339. Epub 2011 Nov 4.
citation: Yie JC, Yang JT, Wu CY, Sun WZ, Cheng YJ. Patient-controlled analgesia (PCA) following video-assisted thoracoscopic lobectomy: comparison of epidural PCA and intravenous PCA. Acta Anaesthesiol Taiwan. 2012 Sep;50(3):92-5. doi: 10.1016/j.aat.2012.08.004. Epub 2012 Sep 7.
citation: Yoshioka M, Mori T, Kobayashi H, Iwatani K, Yoshimoto K, Terasaki H, Nomori H. The efficacy of epidural analgesia after video-assisted thoracoscopic surgery: a randomized control study. Ann Thorac Cardiovasc Surg. 2006 Oct;12(5):313-8.
citation: Fernandez MI, Martin-Ucar AE, Lee HD, West KJ, Wyatt R, Waller DA. Does a thoracic epidural confer any additional benefit following video-assisted thoracoscopic pleurectomy for primary spontaneous pneumothorax? Eur J Cardiothorac Surg. 2005 Apr;27(4):671-4. doi: 10.1016/j.ejcts.2004.12.045.