Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study

Phase 4

Completed

• Conditions: Lung Neoplasms; Pain; Immune Suppression
• Interventions: Drug: Bupivacaine in epidural catheter; Drug: Placebo (for Bupivacain and Fentanyl i epidural catheter); Drug: Fentanyl in epidural catheter; Drug: Oral Paracetamol; Drug: Oral NSAID; Drug: Oral opioids; Drug: Placebo (for oral opioids)

• Registration Number: NCT02359175
• Lead Sponsor: Odense University Hospital

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.

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-04
• Study First Submitted QC: 2015-02-06
• Study First Posted: 2015-02-09
• Primary Completion: 2019-01-24
• Study Completion: 2023-03-22
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-26
• Last Update Posted: 2023-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 161

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.

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Epidural analgesia	Bupivacaine in epidural catheter	Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.
Active Epidural analgesia	Oral NSAID	Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.
Active Epidural analgesia	Placebo (for oral opioids)	Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.
Placebo Epidural analgesia	Oral opioids	Epidural analgesia: Placebo. Oral analgesia: Paracetamol, NSAID and opioids tablets.
Placebo Epidural analgesia	Placebo (for Bupivacain and Fentanyl i epidural catheter)	Epidural analgesia: Placebo. Oral analgesia: Paracetamol, NSAID and opioids tablets.
Active Epidural analgesia	Fentanyl in epidural catheter	Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.
Active Epidural analgesia	Oral Paracetamol	Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.
Placebo Epidural analgesia	Oral Paracetamol	Epidural analgesia: Placebo. Oral analgesia: Paracetamol, NSAID and opioids tablets.
Placebo Epidural analgesia	Oral NSAID	Epidural analgesia: Placebo. Oral analgesia: Paracetamol, NSAID and opioids tablets.

Primary Outcome Measures

Name	Time	Method
Intensity of pain (Self reported pain intensity)	0-4 days	Self reported pain intensity 5 times a day both in rest and during activity until chest tube is removed or day 4 after operation is reached.
Consumption "Rescue Analgesia" - i.v. opioids	0-4 days	The consumption of i.v. opioids is registered daily until chest tube is removed or day 4 after operation is reached.

Secondary Outcome Measures

Name	Time	Method
Sequelae following VATS and placement of epidural catheter	60 months	Questionnaire sent to patients 6, 12, 24 and 60 months after surgery. (criteria edited as part of a protocol amendment July 27th 2016 for a subsequent biomarkers study).
Time used placing epidural catheter	0-4 days	Procedural time and competence level of MD placing catheter
Length of hospital stay	0-4 days	Admission time after surgery.
Side effects of epidural analgesia	0-4 days	Side effects observed using epidural analgesia including itching, nausea, vomiting, procedural pain, hypotension, dizziness, respiratory depression, reduced pulmonary function.
Duration of surgery	0-4 days	The duration of the surgical procedure will be registered.

Trial Locations

Locations (1)

Odense University Hospital; 🇩🇰 Odense C, Denmark