Who will take informed consent? {26a}
Potential participants for this trial will be identified by a member of the surgical, anaesthetic or research team. A member of the research team will analyse these patient’s electronic medical records to determine if they are potential candidates for this trial, i.e., if they meet the inclusion criteria and have no exclusions.
The suitable patient will be approached the evening before surgery if available. Alternatively, patients will be approached on the ward on the morning of surgery and their suitability to participate in the trial will be confirmed. The purpose of the trial, peripheral nerve blocks (including benefits and risks) and method of follow up will be explained to the patient. A comprehensive and informative leaflet will be given to each patient and they will be afforded an adequate amount of time (minimum 10 mins) to study it. Participants will be informed that their participation in the study is entirely voluntary and they will have the opportunity to withdraw from the study at any time and this will not affect the quality of care they receive. Subsequently, a member of the research team will obtain informed written consent from the participant.
Intervention description {11a}
ESP catheter group: Anaesthesiologist-administered, ultrasound guided Erector Spinae catheter [n = 45]
This peripheral nerve block will be performed or supervised by a consultant anaesthesiologist in regional anaesthesia with experience in placement of ESP catheter. The block will be performed as follows: the patient will be positioned in the lateral decubitus position and the skin will be cleaned with chlorhexidine gluconate 0.5%/ isopropyl alcohol 70% solution (ChloraPrep; Becton Dickinson, New Jersey, NJ, USA). A linear ultrasound transducer (SonoSite HFL 50x; SonoSite Inc.) will be placed in a sterile cover. This ultrasound probe will be used to identify the T5 spinous process and the erector spinae muscle group superficial to it. An 18G Tuohy Epidural needle (B. Braun medical) will then be advanced in a cranial-caudal direction. The needle tip will be slowly advanced under ultrasound guidance (In-plane technique) until it is located within the interfascial plane deep to the erector spinae muscle group and superior to the transverse process. Once in position, 10 ml of 0.9% normal saline will be injected to confirm satisfactory needle position. Following this, 20mls 0.375% Leveobupivacaine will be injected and then a 20 G Nylon Epidural catheter (Perifix Epidural Catheter, B. Braun medical) will be advanced into this interfascial plane. The catheter will then be attached to a luer lock connector with an antibacterial filter and secured to the patients back using surgical steri strips and standard dressings. A further bolus of 10mls 0.25% Levobupivacaine will be administered via the catheter towards the end of the surgical procedure (> 1 hour since last dose).
PVB catheter group: Surgeon-administered, video-assisted Paravertebral Block catheter. [n = 45]
This nerve block will be performed or supervised by a consultant thoracic surgeon with experience in placement of paravertebral catheter under thoracoscopic guidance. The paravertebral block will be conducted at the start of the surgery after the thoracoscopic ports have been inserted. The block will be performed as follows: A percutaneous puncture point, which is equidistant to the upper and lower intercostal space, 2-3cm lateral to the midline at the level between T4-T5 will be marked. An 18 G Tuohy Epidural needle (B. Braun medical) will be advanced perpendicularly through the chest wall at this marked point to lie within the paravertebral space. The thoracoscope will be used to ensure that the epidural needle does not puncture the pleura and then 10–20 ml of 0.9% normal saline will be injected through the epidural needle to confirm satisfactory position of the needle. This will appear as an induration under the pleura which can be easily seen thoracoscopically. A 20 G Nylon Epidural catheter (Perifix Epidural Catheter, B. Braun medical) will then be advanced into the paravertebral space through the epidural needle. Again, the thoracoscope will be used to ensure that the epidural catheter does not puncture the pleura and lies within the paravertebral space. The catheter will then be attached to a luer lock connector with an antibacterial filter and secured to the patients back using surgical steri strips and standard dressings. A bolus of 20 ml 0.375% levobupivacaine will then be injected into the paravertebral space by using the catheter.
A further bolus of 10mls 0.25% Levobupivacaine will be administered via the catheter towards the end of the surgical procedure (> 1 hour since last dose)
Participant timeline {13}
The schedule of enrolment, interventions and assessments is outlined in Fig. 3.
Sample size {14}
Data will be recorded in Excel (Microsoft™) and imported into GraphPad Prism v8 for analysis. All data will be stored according to EU Directive 2019 on General Data Protection Regulations. Data will be inspected and tested for distribution according to the Kolmogorov-Smirnov test. Normally distributed data will be compared between study arms using the unpaired t test, whereas non-normally distributed data will be compared using Mann-Whitney U test. All data will be summarised as mean ± SD or median (25–75% range) as appropriate.
Data will be analysed by GraphPad Prism version 8 (GraphPad, Salt Lake City, UT, USA). The primary outcome will be the QoR-15 score at 24 and 48 hours post operatively. The established minimum clinically important difference in QoR-15 is 8.017 and the SD of QoR-15 scores is typically between 10–16. [range of QoR score is 1-150]. We have chosen a SD of 12 to reflect our study population. Therefore, assuming Type I error = 0.05 and Type II error = 0.2 (80% power to detect this difference), then n = 36 patients will be required in each group. We aim to enroll n = 40 each group to allow for loss to follow up, missing data or withdrawal of consent.
Recruitment {15}
Members of the anaesthestic, surgical and research team from the clinical site will participate in the recruitment process.
Assignment of interventions: allocation
Sequence generation {16a}
Patients will be randomised to either ESP or PVB group by using an online computer-generated block randomisation. Block randomisation will occur in groups of 10 to ensure even numbers of participants in each arm of the study. The investigators for this trial will not have access to the randomisation key/seed until the study has been completed.
Concealment mechanism {16b}
The patient study number and group allocation will be typed onto separate pages and concealed in sequentially numbered, opaque, sealed envelopes. The randomisation process will be performed by an independent third party that is not involved conducting this trial.
Implementation {16c}
After confirming the informed consent form for participating in this trial has been signed by the participant, the sealed envelope will be opened by the treating anaesthesiologist to reveal the group allocation. This process will occur after induction of general anaesthesia to ensure the patient is blinded to the study intervention.
Assignment of interventions: Blinding
Who will be blinded {17a}
This study will be a double-blinded clinical trial. Patients will be blinded to the study because they will receive the intervention after they have been put under GA. Members of the research team involved in the data collection and analysing the data will be masked to group allocation. The treating anaesthesiologist and surgical team will not be blinded
Procedure for unblinding if needed {17b}
A participant’s allocations will be revealed immediately if there was a clinical concern, i.e., If patient met criteria for discontinuing study protocol (part 11b).
Data collection and management
Plans for assessment and collection of outcomes {18a}
Data collection will occur at three time points (Pre-operative, Intra-operative and post-operative). Data will be derived from a combination of electronic & paper patient records and directly from the patient by means of completing a questionnaire. In addition, further post-operative data (assessing for CPSP) will be collected by phone call after the patient has been discharged. The same member of the research team (blinded to the intervention) will collect all peri-operative data.
Plans to promote participant retention and complete follow-up {18b}
Trial participants will receive an extensive patient information leaflet (PIL) about the study. A member of the research team will explain this PIL, study set-up and the study interventions. The three-month follow up call for assessment of CPSP will be explained to the patient during the consent process. The importance of completion of this follow up will be stressed.
Data management {19}
All patient data collected will be handled in accordance with European Union General Data Protection Regulations (EU 2016/679). Data will be initially collected manually and then transcribed onto Microsoft Excel. Data collected from the clinical site will be stored securely in the Department of Anaesthesiology at the site hospital, on a password-protected desktop computer stored in a locked office, such that only investigators assigned to data input, processing and analysis will have access. Data will be collected directly from source documents into the de-identified encoded paper Case Record Form (CRF) and subsequently entered into the electronic CRF. A copy of the original hardcopy CRF will be stored within a locked cabinet/office accessible to authorised personnel only in accordance with local and national regulations.
Confidentiality {27}
All research data will be stored using a study identification number for each patient. An identifiable patient data page reporting the assigned patient identification code will be stored separately also in a locked cabinet/office (accessible to authorised personnel only) in order to record in-hospital outcomes, post-operative 3-month follow up, supply missing data points, and to allow potential monitoring visits by National Coordinating Investigators. This data page will only be made available to members of the research team responsible for data input and the principal investigator. No patient identification details will be reported in any future publications.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Not applicable, no samples will be collected.
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
The collected raw data will be initially inspected for any errors, this includes but is not limited to double entry errors, missing data and data that was incorrectly entered. The data will be tested for normal distribution according to the Shapiro-Wilk test. Normally distributed data will be compared between the two groups using the unpaired student t test and non-normal distributed data will be compared by using Mann-Whitney U test. All data will be summarised as mean ± SD and p value < 0.05 will be considered statistically significant.
Interim analyses {21b}
There are no interim analyses planned.
Methods for additional analyses (e.g. subgroup analyses) {20b}
There are no subgroup analyses planned.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
The primary outcome will be assessed using an unpaired student t test analysis. Or Mann-Whitney U test, depending on data distribution. Given our expectation that very few patients will be lost to follow-up during their inpatient stay and protocol adherence strategies as mentioned above, we expect missing data will be reduced to a minimum when analysing the primary outcome. If statistical method is needed to account for missing data in the secondary outcomes (e.g., CPSP survey at 3-month follow up), multiple imputation will be used.
Plans to give access to the full protocol, participant level-data and statistical code {31c}
The collated data collected by the investigators will be retained for a maximum 5 years after analysis has been completed. We will deliver a completely de-identified data set an appropriate data upon reasonable request and in agreement with the principal investigator and data protection officer.
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
The Trial steering committee will meet monthly to evaluate progress, address ongoing organisational and logistical issues and consider any adverse effects. There will be a research leader for the clinical site of whom will provide monthly reports to the principal investigator.
Composition of the data monitoring committee, its role and reporting structure {21a}
A data monitoring committee (DMC) has not been appointed for this study. A data protection impact assessment (DPIA) screening tool was completed, and it was analysed by the hospital’s data protection officer (DPO). In agreement with the DPO, this study poses a low risk to the rights and freedoms of natural persons and therefore a formal DPIA was not needed. Moreover, due to the rapid expected inclusion of participants to this trial, data collection is expected to be completed in less than nine months and known minimal inherited risks associated with this trial, a DMC was not appointed.
Adverse event reporting and harms {22}
Any unexpected complications that may arise from this trial will be documented and reported to the principal investigator, surgical consultant and to the relevant hospital patient safety board.
Frequency and plans for auditing trial conduct {23}
For the purpose of this trial, an initial auding process maybe conducted using a risk-based approach. This would initially involve focusing on a center which may have the largest number of enrolment and/or lost of follow-up rates. The auditing process would include exploring datasets and analysing for accuracy, missing data, duplicate data and adhering to data protection guidelines. This process would be conducted by an independent reviewer who has no involvement with the current trial (e.g., research nurse that is affiliated with the clinical site but is not involved with the current trial).
A research nurse affiliated with MMUH anaesthesiology but not involved in this trial may undertake an audit involving exploring datasets from this and the other institution. This would be precipitated by risk indices including high rates of enrolment and drop-out rates.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
We define a substantial modification of the study protocol as changes which may affect the outcome of the study or patient safety. Changes include: any modification to the aims of the study, study design, the inclusion or exclusion criteria or any alternations of the study interventions (using new procedural equipment or conducting intervention which deviate original description). Any amendment will be agreed upon the principal investigator of this trial and will seek approval by the Ethics Committee/IRB. Minor changes of the protocol include any administrative changes or alternation of the analgesia plan that do not impact patient safety or the conduct of the trial (e.g., changes to anti-emetic medications). The Ethics Committee/IRB may be notified of minor changes at the discretion of the principal investigator.
Dissemination plans {31a}
The results from this clinical trial will be fully disclosed by means of publication in an international peer-reviewed journal and by oral/poster presentations at national & international scientific meetings. Both positive and negative results will be reported.