Clinical Trial Results:
Erector Spinae plane block for minimal invasive mitral valve surgery. A double blind, prospective randomized placebo-controlled trial.
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Summary
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EudraCT number |
2019-001125-27 |
Trial protocol |
BE |
Global end of trial date |
04 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Oct 2022
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First version publication date |
26 Oct 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DH022019
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
UZ Leuven
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Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
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Public contact |
Anesthesiology Research, University Hospitals Leuven, 0032 16344270, christel.huygens@uzleuven.be
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Scientific contact |
Anesthesiology Research, University Hospitals Leuven, 0032 16344270, christel.huygens@uzleuven.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 May 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Nov 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Nov 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The goal of this study is to improve pain management after minimal invasive mitral valve surgery and to facilitate postoperative recovery. Our hypothesis is that patients having an Erector Spinae Block via intermittent boli ropivacain via catheter is associated with a reduction in postoperative morphine consumption.
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Protection of trial subjects |
Patients received acetaminophen (15 mg kg-1) every 6 hours and morphine patient-controlled intravenous analgesia (PCIA) up to 24 hours post-extubation. Rescue analgesia consisted of a bolus of morphine, ketorolac, acetylsalicylic acid and/or removal or infiltration of chest tubes according to a standardized flowchart (supplementary figure S1). Twenty-four hours post-extubation, morphine PCIA was stopped and further analgesic treatment consisted of acetaminophen combined with tramadol or morphine.
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Background therapy |
Irrespective of group allocation, every patient received a bolus of IV morphine (0.1 mg kg-1) and acetaminophen IV (1g) at thorax closure. After having received the interventional treatment, patients were transferred intubated to the PACU under analgosedation with dexmedetomidine and remifentanil. Following extubation (T0), patients received PCIA pump with morphine (on-demand-only mode with a morphine bolus of 1.5 mg up to every 7 minutes). | ||
Evidence for comparator |
While in numerous case reports the ESP block has been described to adequately provide perioperative analgesia after adult cardiac surgery, the evidence from randomized controlled trials (RCT) is scarce. In the four RCTs that investigated the ESP block in adult cardiac surgery, bilateral ESP blocks were used for cardiac surgery cases requiring a sternotomy. In addition, double-blinding of allocation was limited to only 1 trial. | ||
Actual start date of recruitment |
02 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 72
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Worldwide total number of subjects |
72
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EEA total number of subjects |
72
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
33
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From 65 to 84 years |
39
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment details: 112 patients between July 2nd 2019 and November 4th 2021 were screened of whom 72 were eligible for participation. | |||||||||
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Pre-assignment
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Screening details |
All consecutive adult patients scheduled for either MIMVS were evaluated for enrollment according to the inclusion criteria. They were included if 18-80 years of age, BMI <35, EuroSCORE <3, admitted to the PACU with our epilepsy, chronic opioid use or OSAS without treatment. | |||||||||
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Period 1
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Period 1 title |
Surgery (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||
Blinding implementation details |
All patients were randomized through a computer-generated permuted block randomisation sequence (variable block-size with 1:1 allocation). Enclosing assignments in opaque, sequentially numbered, sealed envelopes ensured allocation concealment. Following uneventful surgery and confirmation of post-anesthesia care unit (PACU) admittance, the envelope was opened by research personnel and the trial medication was prepared. Syringes were then labelled with the mark “trial medication”.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention | |||||||||
Arm description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Ropivacaine 0,5%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Injection
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Dosage and administration details |
Dosage and administration details:
Initial dose of 30mL followed after 6, 12 and 18 hours with a dose of 20mL.
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Arm title
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Control | |||||||||
Arm description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
normal saline 0.9%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Injection
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Dosage and administration details |
Dosage and administration details:
Initial dose of 30mL followed after 6, 12 and 18 hours with a dose of 20mL.
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | ||
Reporting group title |
Control
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | ||
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End point title |
Morphine consumption 24 hours | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Assessed 24 hours after extubation
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| Notes [1] - 2 early withdrawals due to 1 reintubation and 1 ischemic cerebral accident. [2] - 2 early withdrawals due to epileptic seizure |
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Statistical analysis title |
Primary outcome | ||||||||||||
Comparison groups |
Intervention v Control
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Number of subjects included in analysis |
68
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Variability estimate |
Standard deviation
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| Notes [3] - Mann-Whitney U test |
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End point title |
Numerical rating score for pain | ||||||||||||
End point description |
Pain intensity as assessed with an 11-point numeric rating score (NRS) for pain
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End point type |
Secondary
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End point timeframe |
Pain scores assessed 2 hours after extubation
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| Notes [4] - 2 early withdrawals due to 1 reintubation and 1 ischemic cerebral accident [5] - 2 early withdrawals due to epileptic seizure |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From enrollment until 24 hours after extubation.
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Adverse event reporting additional description |
Incidence of adverse events (AE) related to the intervention or surgical procedure.
Early safety endpoints at 30 days as defined by Valve Academic Research Consortium-2 (VARC-2) (all-cause mortality, stroke, life-threatening bleeding, acute kidney injury (stage 2 or 3), major vascular complication or valve-related dysfunction) will be evaluated.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25
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Reporting groups
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Reporting group title |
Intervention
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
After completion of the surgery, an ESP block (with placement of a catheter) was performed with 30mL of trial medication. There after, 20mL trial medication through the ESP-catheter at the PACU was given every 6 hours after the first dose (B0 +6h, B0 +12h, and B0 +18h), three times in total. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Mar 2021 |
Extension of recruitment period due to COVID-19 Pandemic. In addition, the planned blinded interim analysis for sample size recalculation (September 22nd 2020) revealed the need to include 4 additional patients in each group. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
