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Trial registered on ANZCTR


Registration number
ACTRN12613000813785
Ethics application status
Approved
Date submitted
21/07/2013
Date registered
24/07/2013
Date last updated
30/07/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does preemptive hydromorphone and ropivacaine thoracic epidural analgesia have clinical benefits?
Scientific title
Comparison of perioperative clinical benefits of preemptive vs. conventional thoracic epidural analgesia with hydromorphone and ropivacaine in patients undergoing thoracotomy
Secondary ID [1] 282873 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
This study compares clinical perioperative analgesia and hemodynamic stability and outcome between preemptively applied thoracic epidural patient controlled analgesia and that applied at the end of surgery in patients undergoing lung surgery under open thoracotomy. 289691 0
Condition category
Condition code
Anaesthesiology 290010 290010 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
patients scheduled for open thoracotomy with a thoracic epidural catheter inserted on the previous day of the surgery, were randomly allocated to one of two groups.

The Preemptive Group is the intervention group in this trial.

1) thoracic epidural analgesia (TEA) applied preemptively before surgery (Preemptive group)

2) thoracic epidural analgesia (TEA) applied at the end of surgery (Nonpreemptive group)


After induction of anesthesia, patients in Preemptive group received 10ml 0.1% ropivacaine with 100 ug hydromorphone via an indwelling epidural catheter followed by a continuous infusion with an infusion pump (Aim(Registered Trademark) plus, Abbott Laboratories, U.S.A) at least 30 minutes before surgical incision.

Patients in Nonpreemptive group received the same epidural 10ml drug administration and a continuous TEA regimen at the end of surgery.

A continuous TEA regimen for both groups was comprised of 0.15% ropivacaine with 8ug/ml hydromorphone at the rate of basal 5ml/hr and a 3ml bolus with a 15 minute lockout interval.

The incidence of hypotension during surgery was recorded. Hypotension was defined as a persistent decrease of systolic blood pressure greater than 30% of baseline or mean blood pressure less than 60 mmHg, that was not due to a bleeding episode, and that required a continuous infusion of inotropics or vasopressors despite three or more consecutive intravenous (IV) bolus injections of ephedrine or phenylephrine.

The amount of TEA and IV fentanyl administered during surgery was recorded.

Postoperative analgesia was controlled with TEA and rescue IV morphine or oral tramadol and acetaminophen combination (Ultracet(Registered Trademark)).

The duration of this trial is 48 hours.

Postoperative follow up of study
1. Consumption of TEA after surgery was recorded.
Numerical rating scales at rest and cough (NRS, a scale of 0 – 10 in which 0 is no pain and 10 is worst pain) were used to assess the pain severity.

2. The incidence of intraoperative hypotension, and side effects including nausea, pruritis, sedation, hypotension and respiratory depression were recorded at postoperative 2, 6, 24, and 48 hr.

3. Functional vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured by a portable spirometry (Micro, Micro Medical Limited, Rochester, U.K.) before surgery and at postoperative 24 and 48 hr.

4.Persistence of pain and its characteristics on the surgical wound at postoperative 6 month was also investigated.
Intervention code [1] 287575 0
Treatment: Drugs
Comparator / control treatment
comparator : Preemptive group - preemptive application of thoracic epidural analgesia

control : NonPreemptive group - thoracic epidural anagesia applied at the end of surgery, Participants in this group (NonPreemptive group) will receive the same epidural 10ml drug administration and a continuous TEA regimen as participants in the Preemptive group but at the end of surgery
Control group
Active

Outcomes
Primary outcome [1] 290057 0
Difference in numerial rating scale of postoperative pain at postoperative 48 hour between the two groups.
Timepoint [1] 290057 0
postoperative 48 hour
Secondary outcome [1] 303847 0
incidence of intraoperative hypotension during surgery
Timepoint [1] 303847 0
intraoperative hypotension is measured during surgery by invasive arterial blood pressure monitoring.

Hypotension was defined as a persistent decrease of systolic blood pressure less than 30% of baseline or mean blood pressure less than 60 mmHg, that was not due to a bleeding episode, and that required a continuous infusion of inotropics or vasopressors despite three or more consecutive intravenous (IV) bolus injections of 5-10 mg ephedrine or 1 mg/kg phenylephrine.
Secondary outcome [2] 303910 0
incidence of FEV1 and FVC changes from baseline at postoperative 48 hours
Timepoint [2] 303910 0
measured at postoperative 48 hours using portable spirometry (Micro, Micro Medical Limited, Rochester, U.K.)
Secondary outcome [3] 303911 0
incidence of side effects nausea and pruritis at postoperative 24, 48, 72 hours
Timepoint [3] 303911 0
measured at postoperative 24, 48, 72 hours by visiting each patient and requesting on nausea and pruritis
Nausea and pruritis are measured by the scale of none/mild/moderate/severe.
Secondary outcome [4] 303912 0
incidence of hypotension at postoperative 24, 48, 72 hours
Timepoint [4] 303912 0
hypotension was defined as systolic blood pressure less than 80mmHg or mean blood pressure less than 60mmHg.
measured at postoperative 24, 48, 72 hours
Secondary outcome [5] 303913 0
incidence of side effect, sedation at postoperative 24, 48, 72 hours
Timepoint [5] 303913 0
Sedation was assessed on a 5-point scale (1- completely awake with the eyes open; 2 -drowsy; 3 -dozing, 4- mostly sleeping; and 5- not responding) at postoperative 24, 48, 72 hours.
Secondary outcome [6] 303914 0
incidence of chronic pain (neuropathic pain nature) at postoperative 6 month
Timepoint [6] 303914 0
measured at postoperative 6 month, assessed when the patient visited our outpatient clinic for 6 month follow up.
neuropatic pain was dignosed if the patient admitted to have persistent pain at the wound area with descriptions such as "burning", "tingling", "sharp lancinating" etc.

Eligibility
Key inclusion criteria
1. aged between 20-75 years
2. American Society of Physical Status (ASA PS) I-II
3. scheduled for open thoracotomy with a thoracic epidural catheter inserted on the previous day of the surgery
Minimum age
20 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
patients with renal, hepatic, or cardiac dysfunction, neurologic disorder, previous opioids, corticosteroids, or nonsteroidal anti-inflammatory drugs within one week of surgery, previous anticoagulation therapy, allergy to local anesthetics or opioids, or inability to use patient controlled epidural analgesia (PCEA) or perform portable pulmonary function test.

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)
An investigator conducted a processing of randomized allocation according to the group block number, generated by a computer based randomization program (www.randomizer.org) and a concealed envelope technique was used.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer based randomization program (www.randomizer.org)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size was analyzed with a power of 90% and a type I error of 5%, and was calculated to be 10 patients per group to detect the NRS difference of 3 with a standard deviation (SD) of 2 at postoperative 48 hour. At least fifteen patients per group were decided to be enrolled in this study regarding a dropout rate of 50 % during postoperative follow up.

Statistical analysis :SPSS 18.0 (SPSS, Chicago, IL).
The patient characteristics, intraoperative data, TEA and rescue IV fentanyl or morphine consumption, the NRS and PFT parameters: Mann-Whitney’s test with bonferroni’s correction.
The incidence of side effects : chi-square or Fisher’s exact test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5236 0
Korea, Republic Of
State/province [1] 5236 0
Seoul

Funding & Sponsors
Funding source category [1] 287658 0
Self funded/Unfunded
Name [1] 287658 0
Sang Hyun Lee
Address [1] 287658 0
Dongtan Sacred Heart Hospital 40 Sukwoo dong, Hwasung city Gyeunggi do, 445-170
Country [1] 287658 0
Korea, Republic Of
Primary sponsor type
Hospital
Name
Samsung Seoul Hospital
Address
Samsung Seoul Hospital
50 Ilwon dong, Kangnam gu, Seoul, Korea
135-710
Country
Korea, Republic Of
Secondary sponsor category [1] 286396 0
Individual
Name [1] 286396 0
Woo Seog Sim
Address [1] 286396 0
Samsung Seoul Hospital
50 Ilwon dong, Kangnam gu, Seoul, Korea
135-710
Country [1] 286396 0
Korea, Republic Of

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Preemptive analgesia is known to decrease the sensitization of the central nervous system and reduce subsequent amplification of nociceptive stimuli. This study investigates whether preemptive thoracic epidural analgesia (TEA) demonstrates overall clinical advantages during intra and postoperative period.

Patients scheduled for open thoracotomy, are randomly allocated to one of two groups to start TEA either before surgical incision (Preemptive group) or at the end of operation (Nonpreemptive group).
Incidence of hypotension during surgery are recorded. Numerical rating scales for pain and the incidence of side effects such as nausea, pruritis, sedation, hypotension and respiratory depression are recorded at postoperative 2, 6 24, 48 hr. Functional vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) are measured before and 24, 48 hr after operation. Pain control at postoperative 6 month are investigated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41614 0
Prof Woo Seog Sim
Address 41614 0
Samsung Seoul Hospital
50 Ilwon dong, kangnam gu
Seoul Korea
135-710
Country 41614 0
Korea, Republic Of
Phone 41614 0
+82 2 3410 0356
Fax 41614 0
Email 41614 0
anesthe@skku.edu
Contact person for public queries
Name 41615 0
Dr Sang Hyun Lee
Address 41615 0
Dongtan Sacred Heart Hospital
40 Sukwoo dong, Hwasung city
Gyeunggi do
445-170
Country 41615 0
Korea, Republic Of
Phone 41615 0
+82 31 8086 2282
Fax 41615 0
Email 41615 0
shsara.lee@gmail.com
Contact person for scientific queries
Name 41616 0
Dr Sang Hyun Lee
Address 41616 0
Dongtan Sacred Heart Hospital
40 Sukwoo dong, Hwasung city
Gyeunggi do
445-170
Country 41616 0
Korea, Republic Of
Phone 41616 0
+82 31 8086 2282
Fax 41616 0
Email 41616 0
shsara.lee@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary