Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001563853
Ethics application status
Approved
Date submitted
18/09/2021
Date registered
17/11/2021
Date last updated
17/11/2021
Date data sharing statement initially provided
17/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
RESPIRO trial: Rib fracture analgesia with Erector Spinae Plane Catheter comparing efficacy of continuous Infusion versus intermittent bolus regimen
Scientific title
Comparison of worst pain on movement at 48 hours between programmed Intermittent bolus versus continuous infusion of local anaesthesia regimens via erector spinae catheter for rib fractures: A multicentre, randomised, double-blind study
Secondary ID [1] 304986 0
None
Universal Trial Number (UTN)
U1111-1268-5118
Trial acronym
RESPIRO Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rib fracture 323139 0
Pain 323140 0
Pulmonary dysfunction 323141 0
Condition category
Condition code
Anaesthesiology 320713 320713 0 0
Pain management
Injuries and Accidents 321413 321413 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Programmed intermittent bolus regimen of local anaesthetic via a erector spinae catheter for posterior rib fracture analgesia
1. ESP catheter would be inserted by an experienced regional anaesthetist aided by a trained assistant.
2. Monitoring - 3 electrode ECG, pulse oximeter and non-invasive blood pressure
3. Vertebral level selected to correspond to the approximate mid-point of the extent of fractured ribs
4. Sitting or lateral position based on the preference of the patient and the proceduralist
5. A linear array high frequency ultrasound transducer would be used in the parasagittal plane to identify the transverse process and erector spinae muscle
6. Strict aseptic precautions and local skin infiltration with 1% Lignocaine.
7. A catheter would be inserted in the plane to contact the transverse process, and a myofascial plane deep to the erector spinae muscle identified.
8. After the erector spinae plane (ESP) is identified using 5-10ml of 0.9% normal saline the catheter would then be secured with at least 1-2 centimetres of the catheter left in the ESP
9. 24 ml of 0.2% ropivacaine would then be injected under ultrasound guidance. If spread is not visualised, the ESP catheter would be reinserted.
10. Adequacy of catheter location will be confirmed by another researcher not associated with patient recruitment or clinical performance, who will adjudicate if the catheter was placed in the correct plane using saved ultrasonographic images showing at least one of the following features:
• Hydro dissection
• Colour doppler cranio-caudal spread
• Catheter visualisation

11. Histoacryl glue (TBA) would be used to seal the skin puncture site to prevent LA leak.
12. The catheter would be secured using Steri-StripTM (3M Nexcare, USA) and transparent adhesive dressing (TegadermTM, 3M, Maplewood, MN, USA). Catheter will be non tunnelled.
13. Monitoring would be continued for 30 minutes after the procedure.
14. All participants would be initiated on patient-controlled analgesia (PCA)Choice of opioid and bolus dosage at initiation is as below, and usage would be converted using oMEDD. A lockout period of 5 minutes and no background infusion will be programmed.
Drugs used in PCA: Fentanyl (dosages administered 10mcg, 15 mcg and 20 mcg), Oxycodone (dosages administered 1mg, 1.5mg, 2mg), Hydromorphone (dosages administered 200mcg, 300 mcg, 400mcg) as lowest dose, first increment and second increments respectively. 1. Inadequate analgesia defined by an NRS score = 7, or less than a 2-point fall in NRS will be managed by APS as per protocol. 1 hour after the rescue measure, the adequacy of analgesia will be reassessed. Each use of rescue analgesia and timing will be recorded. The dosage will be PCA will be continued for 48 hours and then as per the discretion of acute pain service.
15. Both groups would receive paracetamol 1g 6 hourly orally or intravenously and celecoxib 100 to 200mg mg twice a day if not contraindicated. These will be continued for 48 hours and then as per the discretion of acute pain service.
16. All other analgesics including tramadol, pregabalin, ketamine, tapentadol and tricyclic antidepressants would not be initiated. Analgesics for chronic pain conditions in those who did not meet the exclusion threshold will be continued.
17. If the participant has been allocated to Group PIB (Programmed intermittent bolus): After a delay of 1 hour following catheter insertion, 24 ml of 0.2% ropivacaine would be administered as programmed intermittent bolus every 3 hours. No background infusion would be used. This will be continued for 48 hours and then as per the discretion of acute pain service.
Intervention code [1] 321376 0
Treatment: Devices
Intervention code [2] 321911 0
Treatment: Drugs
Comparator / control treatment
Continous infusion regimen of local anaesthetic via a erector spinae catheter for posterior rib fracture analgesia
If the participant has been allocated to Group CI (continous infusion): Following catheter insertion, patients would be administered 0.2% ropivacaine as a continuous infusion at 8 ml /hour after a delay of 1 hour. The infusion will be continued for 48 hours and then as per the discretion of acute pain service.
Control group
Active

Outcomes
Primary outcome [1] 328834 0
Primary outcome will be 48-hour worst pain on movement
Pain scores would be recorded using 11-point numerical rating scale (NRS) from 0 to 10.
Timepoint [1] 328834 0
48-hour post catheter insertion
Secondary outcome [1] 400572 0
24 and 48-hour worst pain at rest. Pain scores would be recorded using 11-point numerical rating scale (NRS) from 0 to 10.
Timepoint [1] 400572 0
24 and 48 hours post-catheter insertion
Secondary outcome [2] 401731 0
24 worst pain on movement. Pain scores would be recorded using 11-point numerical rating scale (NRS) from 0 to 10.
Timepoint [2] 401731 0
24 hours post cathater insertion
Secondary outcome [3] 401732 0
24 and 48-hour oral morphine equivalent per day (oMEDD) consumption. The cumulaive opioid consumption per day will be calculated from patient medical records. The PCA pump will show 24 hours opioid consumption and this will be recoreded in patient medical records.
Timepoint [3] 401732 0
24 and 48 hours post catheter insertion
Secondary outcome [4] 401733 0
24 and 48-hour spirometry FVC and PEF
Timepoint [4] 401733 0
24 and 48 hour post catheter insertion
Secondary outcome [5] 401734 0
Hospital length of stay (LOS). This will be calculated from patient medical records.
Timepoint [5] 401734 0
On discharge from hospital
Secondary outcome [6] 401735 0
Patient satisfaction score using a 5-point Likert score at 24 and 48 hours
Timepoint [6] 401735 0
24 and 48 hours post catheter insertion

Eligibility
Key inclusion criteria
1. Adults, aged 18 and older
2. With greater than or equal to 2 ipsilateral rib fracture posterior to the midaxillary line
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Mechanical ventilation
2. Inability to use patient-controlled analgesia (PCA)
3. Inability to consent and comprehend numerical rating scale (NRS) (head injury, cognitive impairment, insufficient English language proficiency)
4. Chronic opioid use; defined as > 40mg oMEDD in the week prior to admission
5. Allergy to ropivacaine
6. Other rib fractures- eg.ipsilateral anaterior, bilateral ribs fractures

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following successful randomisation, each patient will be assigned a unique patient study number to maintain confidentiality. Allocation concealment is maintained using opaque sealed envelopes prepared by a person not involved in the study, based on randomisation through RedCAP. This is done prior to recruitment. Only trained investigators or research assistants will have access to REDCap for the randomisation process. Once the patient is recruited, the sealed envelop is handed over to the clinical team who initiates treatment based on the intervention mentioned in the envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible patients will be randomised in a 1:1 ratio, in permuted blocks of size 4, stratified according to site and sex via the password protected web-based interface, REDCap. Only trained investigators or research assistants will have access to REDCap for the randomisation process and data entry. Following successful randomisation, each patient will be assigned a unique patient study number to maintain confidentiality.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Baseline patient characteristics will be summarised using descriptive statistics. Analysis will be on an intention-to-treat basis. The primary outcome of worst dynamic numerical pain score at 48 hours will be analysed using an ordinal generalised linear mixed model, adjusted for baseline numerical pain score, with a random effect for participating site. A minimal adjustment set, derived through a directed acyclic graph (DAG) will be used to determine variables a priori that are prognostic for the primary outcome. Model fit will be assessed using the likelihood ratio test and information criterion. Collinearity between the variables will be assessed using the variance inflation factor (VIF). Missing data will be addressed with multiple imputation.

Comparisons between groups for secondary outcomes of static and dynamic pain, opioid consumption, spirometry, hospital length of stay and patient satisfaction score will be estimated as differences in medians (for continuous outcomes), risk ratios (for binary and ordinal outcomes) and hazard ratios (for time-to-event outcomes). No correction for multiple testing will be applied.

Statistical analyses will be performed using R Version 4.0.3 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria) and RStudio Version 1.4.1103 (RStudio, PBC, Boston, MA). R packages used for analysis include Tidyverse, Ordinal, ggplot2, Performance and gtsummary. p values <0.05 will be considered significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/11/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20463 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 20464 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 20465 0
Gosford Hospital - Gosford
Recruitment hospital [4] 20466 0
John Hunter Hospital - New Lambton
Recruitment hospital [5] 20467 0
Wagga Wagga Base Hospital - Wagga Wagga
Recruitment postcode(s) [1] 35232 0
2747 - Kingswood
Recruitment postcode(s) [2] 35233 0
2170 - Liverpool
Recruitment postcode(s) [3] 35234 0
2250 - Gosford
Recruitment postcode(s) [4] 35235 0
2305 - New Lambton
Recruitment postcode(s) [5] 35236 0
2650 - Wagga Wagga

Funding & Sponsors
Funding source category [1] 309598 0
Government body
Name [1] 309598 0
Nepean Blue mountain local health district
Country [1] 309598 0
Australia
Funding source category [2] 309871 0
Hospital
Name [2] 309871 0
Wagga Wagga Hospital
Country [2] 309871 0
Australia
Funding source category [3] 309872 0
Hospital
Name [3] 309872 0
Liverpool Hospital
Country [3] 309872 0
Australia
Funding source category [4] 309873 0
Hospital
Name [4] 309873 0
John Hunter hospital
Country [4] 309873 0
Australia
Funding source category [5] 309874 0
Hospital
Name [5] 309874 0
Gosford hospital
Country [5] 309874 0
Australia
Primary sponsor type
Hospital
Name
Nepean Hospital- Nepean Blue mountain LHD
Address
Derby Street, Kingswood, NSW 2747
Country
Australia
Secondary sponsor category [1] 310738 0
None
Name [1] 310738 0
Address [1] 310738 0
Country [1] 310738 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309187 0
Nepean Hospital HREC
Ethics committee address [1] 309187 0
Ethics committee country [1] 309187 0
Australia
Date submitted for ethics approval [1] 309187 0
Approval date [1] 309187 0
31/08/2021
Ethics approval number [1] 309187 0
2021/ETH01317

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113274 0
Dr Tim Thomas Joseph
Address 113274 0
Nepean Hospital, Derby street, Kingswood, NSW 2747
Country 113274 0
Australia
Phone 113274 0
+61 451100665
Fax 113274 0
Email 113274 0
tim.joseph@health.nsw.gov.au
Contact person for public queries
Name 113275 0
Tim Thomas Joseph
Address 113275 0
Nepean Hospital, Derby street, Kingswood, NSW 2747
Country 113275 0
Australia
Phone 113275 0
+61 247342000
Fax 113275 0
Email 113275 0
tim.joseph@health.nsw.gov.au
Contact person for scientific queries
Name 113276 0
Tim Thomas Joseph
Address 113276 0
Nepean Hospital, Derby street, Kingswood, NSW 2747
Country 113276 0
Australia
Phone 113276 0
+61 247342000
Fax 113276 0
Email 113276 0
tim.joseph@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available publicly as there is confidential information only for research analysis. We have a RDMP plan for ethical purposes.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.