The Effectiveness of ThOracic Epidural and Paravertebral Blockade In Reducing Chronic Post- Thoracotomy Pain: 2 (TOPIC-2)

• ClinicalTrials.gov Identifier: NCT03677856
• Recruitment Status: Recruiting
• First Posted: September 19, 2018
• Last Update Posted: September 26, 2019
• Sponsor: University of Birmingham
• Information provided by (Responsible Party): University of Birmingham

Study Description

Brief Summary:

An estimated 7200 thoracotomies (surgical incision into the chest wall) are performed annually in the UK, most commonly to treat lung cancer. It is considered one of the most painful surgical procedures due to tissue, muscle and nerve damage from the incision, and as the wound heals. The normal breathing motion and nerve injury caused during surgery can result in a high risk of persistent pain for months after surgery. Chronic post-thoracotomy pain (CPTP) is defined as pain that recurs or persists at least two months following the surgery and can occur in up to half of these patients.

There are two commonly used for pain control during thoracotomy: Thoracic Epidural Block (TEB) blocks nerves on both sides of the chest at the spinal cord. It reduces painful nerve signals but may not abolish them completely. Para Vertebral Blockade is done only on the side of surgery and may completely block painful nerve signals from reaching the spinal cord. This total blockade of nerve signals could decrease the likelihood of developing chronic pain and could be uniquely effective in preventing long-term pain.

Over a period of 30 months this trial will be attempting to approach all patients undergoing a thoracotomy at approximately 20 UK hospitals to see if they wish to participate, and to look at the reasons they may not want to participate. We will follow up each participant for a maximum of a year following their surgery.

There is a qualitative intervention embedded within this study to support recruitment.

Condition or disease	Intervention/treatment	Phase
Anesthesia; Thoracic Diseases	Procedure: Paravertebral blockade; Procedure: Thoracic epidural block	Not Applicable

Detailed Description:

At the present time, both thoracic epidural block (TEB) and paravertebral blockade (PVB) are routinely used in the UK to provide pain relief for patients undergoing elective open thoracotomy. TEB has long been regarded as the 'gold standard' technique of pain relief for thoracotomy but this has recently been challenged from an overview of the literature on trends and new evidence in the management of acute and chronic post-thoracotomy pain.

In TOPIC 2 the interventional arm will be peri-operative (at or around the time of surgery) pain relief using PVB and the comparator arm will be peri-operative pain relief using TEB. The only pre-operative change to the patient pathway in TOPIC 2 is that the patient will be approached during pre-operative assessment at least 24 hours prior to surgery.

Post-operatively patients will receive analgesia in line with current practice. The trial's hypothesis is that in adult patients undergoing elective open thoracotomy, the use of paravertebral blockade for pain relief at or around the time of surgery reduces both the number of people reporting chronic pain and the persistence of chronic pain at six months by at least 10%, compared with the use of thoracic epidural block. To detect this difference a total of 1026 patients will be recruited from approximately 20 UK hospitals.

Interim analyses of safety and efficacy for presentation to the independent DMC will take place during the study. The committee will meet prior to study commencement to agree the manner and timing of such analyses but this is likely to include the analysis of the primary and major secondary outcomes and full assessment of safety (SAEs) at least at annual intervals. Criteria for stopping or modifying the study based on this information will be ratified by the DMC, but there is also an embedded pilot phase which sets out criteria for assessing whether sufficient progress is made during the first 12 months of recruitment. Failure to open enough sites to recruitment or recruit enough patients from those sites, may be sufficient reason to terminate the trial, or at least re-design some of it to ease these problems.

A randomised controlled trial design has been chosen since this is the acknowledged "gold standard" for evidence based medicine and, because only the patients themselves can say how much pain they are in, patient reported outcomes are appropriate in answering the trial question. Because of the nature of the procedure it is not possible to conceal the surgical team performing the procedure from the allocation but they will not know in advance which of the allocated treatments will be received. There is no reason to believe that patients will have any preconceptions regarding the levels of chronic pain they will experience so the chance of bias is low in this regard.

TOPIC 2 has been designed as a pragmatic trial which collates data during the hospital admission for thoracotomy then, by telephone interview and postal questionnaire at 3, 6 and 12 months. This schedule of events as well as both the type and amount of data collected has been created with substantial input from 2 patient/public representatives.

Since the track record of recruitment to trials involving surgery is not as good as in other areas of medicine, the trial has embedded a qualitative component which will specifically look at the consent process and the reasons for patients either entering or not entering the trial. Patients will therefore initially be asked to consent to the conversation introducing the trial being recorded, and to participate in the main trial. They can choose to participate in just the interview process (conducted in the clinic), just the main trial, neither, or both.

The trial documentation has been prepared in advance of submission to ethics and recruitment is estimated to start in the final quarter of 2018, for 30 months. The first 12 months of recruitment will form an internal pilot phase during which the feasibility of the overall trial will be assessed. Although the primary outcome requires only 6 months followup, patients will be followed up for year to provide a further estimate of how long any differences in pain levels lasts. It will take approximately a further 6 months to analyse the data prior to publication.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1026 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multi-centre, parallel group, superiority, with an internal pilot, in a 1:1 ratio
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised Controlled Trial to Investigate the Effectiveness of ThOracic Epidural and Paravertebral Blockade In Reducing Chronic Post- Thoracotomy Pain: 2
• Actual Study Start Date: January 8, 2019
• Estimated Primary Completion Date: January 8, 2022
• Estimated Study Completion Date: October 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Paravertebral Blockade; Anaesthesia to single side of the patient's chest	Procedure: Paravertebral blockade; Type of anaesthesia
Active Comparator: Thoracic epidural block; Anaesthesia to both sides of the patient's chest	Procedure: Thoracic epidural block; Type of anaesthesia

Outcome Measures

Primary Outcome Measures :

1. Incidence of chronic pain: incidence = score > 40 on visual analogue score [ Time Frame: 6 months post trial thoracotomy ]
   Patient reported pain lasting at least 3 months as measured by visual analogue score

Secondary Outcome Measures :

1. Complications of regional anaesthesia [ Time Frame: 3, 6 and 12 months post randomisation ]
   Complications of regional anaesthesia are protocol-defined
2. Incidence of surgical complications [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
   as classified by the European Society of Thoracic Surgeons
3. Incidence of surgical complications [ Time Frame: 3, 6 and 12 months post randomisation ]
   as classified by the European Society of Thoracic Surgeons
4. Incidence of Major Post-operative pulmonary complications [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
   as classified by StEP Core Outcome Measures in Perioperative and Anaesthetic Care
5. Incidence of Major Post-operative pulmonary complications [ Time Frame: 3, 6 and 12 months post randomisation ]
   as classified by StEP Core Outcome Measures in Perioperative and Anaesthetic Care
6. Incidence of critical care admission [ Time Frame: 3, 6 and 12 months post randomisation ]
   Any admission to critical care extracted from hospital records
7. Mortality [ Time Frame: 3, 6 and 12 months post randomisation ]
   All deaths due to all causes
8. Analgesic use [ Time Frame: 3, 6 and 12 months post randomisation ]
   all forms of analgesic use for trial-related pain as reported by patient
9. Acute pain [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
   Patient reported worst chest pain on visual analogue scale (0-10) with 10 being the worst
10. Acute pain [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
    Patient reported via Brief Pain Inventory Interference score (0-10, higher = worse)
11. Acute pain [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
    Patient reported worst chest pain via Short Form McGill Pain Score (0-10 higher = worse score)
12. Acute pain [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported worst chest pain on visual analogue scale (0-10) with 10 being the worst
13. Acute pain [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported worst chest pain via Brief Pain Inventory Interference Score (0-10 higher = worse score)
14. Acute pain [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported worst chest via Short Form McGill Pain Score (0-10 higher = worse score)
15. Health resource use [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
    Targeted collection of health resource use data from hospital records
16. Health resource use [ Time Frame: 3, 6 and 12 months post randomisation ]
    Targeted collection of health resource use data from hospital records
17. General health-related quality of life Index Score [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported using EQ-5D-5L questionnaire Index Score (1.0 = best outcome)
18. General health-related quality of life Thermometer Score [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported using EQ-5D-5L questionnaire Thermometer Score (0-100, 100 = best outcome)
19. General health-related quality of life [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
    Patient reported using Hospital Anxiety and Depression Score (0-21, lower = better)
20. General health-related quality of life [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported using Hospital Anxiety and Depression Score (0-21, lower = better)
21. Patient Satisfaction with care provided [ Time Frame: Until discharge from hospital post randomisation eg a maximum of 30 days ]
    Patient reported on Likert scale (Very dissatisfied/ Dissatisfied/ Satisfied/ Very satisfied)
22. Patient Satisfaction with care provided [ Time Frame: 3, 6 and 12 months post randomisation ]
    Patient reported on Likert scale (Very dissatisfied/ Dissatisfied/ Satisfied/ Very satisfied)
23. Incidence of Serious Adverse Events [ Time Frame: 3, and 6 months post randomisation ]
    Protocol-defined events meeting the accepted trial definition of "serious"

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Aged ≥18 years
• Elective open thoracotomy
• Able to provide written informed consent
• Willingness to complete study questionnaires up until 12 months post randomisation

Exclusion Criteria:

• Contraindication to TEB or PVB e.g. known allergy to local anaesthetics; infection near the proposed puncture site; coagulation disorders, thoracic spine disorders
• Surgery for chest wall pathology on the side of surgery
• Previous thoracotomy
• Median sternotomy within 90 days

Contacts and Locations

Contacts

Contact: Hugh Jarrett, MSc; 00 44 121 415 9134; h.jarrett@bham.ac.uk

Locations

United Kingdom

Heartlands Hospital; Recruiting

Birmingham, West Midlands, United Kingdom

Contact: Babu Naidu

Sponsors and Collaborators

University of Birmingham

Investigators

• Principal Investigator: Fang Gao Smith, MD; University of Birmingham

More Information

• Responsible Party: University of Birmingham
• ClinicalTrials.gov Identifier: NCT03677856
• Other Study ID Numbers: RG_18-0108
• First Posted: September 19, 2018
• Last Update Posted: September 26, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: The final data set itself will only be available to the direct TOPIC 2 Trial Team, including the Trial Steering Committee (TSC), in the first instance. It will also be made available upon formal request when the reason for the request is approved by the TSC.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Birmingham:

Paravertebral block; Thoracic epidural block; Thoracotomy

Additional relevant MeSH terms:

Thoracic Diseases; Respiratory Tract Diseases