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Trial registered on ANZCTR


Registration number
ACTRN12617000889358
Ethics application status
Approved
Date submitted
7/05/2017
Date registered
16/06/2017
Date last updated
16/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Perioperative Pregabalin as an Adjunct in Adolescent Scoliosis Surgery
Scientific title
Randomised Controlled Trial of Perioperative Pregabalin as an Adjunct in Adolescent Idiopathic Scoliosis Surgery - effect on post-operative pain control and anxiety score
Secondary ID [1] 291275 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adolescent Idiopathic Scoliosis 303164 0
Condition category
Condition code
Anaesthesiology 302607 302607 0 0
Pain management
Mental Health 302608 302608 0 0
Anxiety
Musculoskeletal 302879 302879 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aims to determine the efficacy of perioperative pergabalin as an adjunct in adolescent idiopathic scoliosis surgery. A total of 68 patients are assigned into 2 groups - treatment (PRE) group vs placebo (PLA) group.

The patient will then receive either single dose oral pregabalin 50mg (in the PRE group) or placebo capsule (in the PLA group) preoperatively. In the ward, further 4 more doses of oral pregabalin 50mg or placebo will be served 12 hourly at post-operation 12 hours, 24 hours, 36 hours and 48 hours post-operatively.

The following assessments will be carried out at various time intervals : On the day of admission, pre-operation (one hour after drug administration); post operation 0 hour at PACU, post-operation 4 hours; 8 hours; 12 hours; 24 hours; 48 hours; and 72 hours in the ward.

1. Pain assessment VAS/NRS*
2. Total consumption of patient controlled analgesic (PCA) morphine
3. Frequency of breakthrough pain requiring rescue analgesia in PACU
4. Validated Visual Analog Scale for anxiety (VAS-A)*
5. The anxiety component of the Hospital Anxiety Depression Score (HADS)*
6. Richmond Agitation and Sedation Scale (RASS)*
7. Incidence of nausea, vomiting, sedation, headache, dizziness, visual disturbances and dry mouth.

To assess incidence of neuropathic pain post-operation, patient will be assessed using painDETECT questionnaire at 2 weeks, 1 month and 6 months post-operation via phone call.

Anaesthetic Protocol
The standardized anaesthetic protocol will be applied to both groups of patients.

All patients are adequately fasted prior to surgery. Induction of anaesthesia is carried out with intravenous Propofol 2-4mg/kg, target-controlled-infusion (TCI) of intravenous Remifentanil with target effect-site concentration (Cet) of 1 to 5 ng/ml (Minto model), and Intravenous rocuronium 0.9mg/kg followed by endotracheal intubation.
Anaesthesia is maintained with inhalational Desflurane at Minimum Alveolar Concentration (MAC) of 0.6 to 0.8 and ventilate with 50% oxygen/air mixture. Standard patient’s monitoring includes continuous invasive arterial blood pressure monitoring, heart rate, pulse oximetry, 3-leads electrocardiogram and Bispectral index (BIS) of 40-60.
Intraoperative cell salvage technique is use as blood conservation strategy and Ringer’s lactate solution as maintenance fluid therapy.

Intraoperative analgesia is provided by TCI Remifentanil at set target of 2-5 ng/ml. Before the surgery is ended, patient will receive the following analgesics:
1. Intravenous Morphine 0.2mg/kg – 45 minutes before skin closure
2. Intravenous Paracetamol 15mg/kg – 30 minutes before skin closure
3. Intravenous Fentanyl 1mcg/kg – 10 minutes before skin closure

At the end of operation, patients will be reversed with IV neostigmine 0.05mg/kg and IV atropine 0.02mg/kg, TCI remifentanil tapered off, and patient will be extubated after meeting criteria for extubation.

All patients will receive post-operative nausea and vomiting prophylaxis in the form of is IV dexamethasone 0.10 mg/kg at induction and IV ondansetron 0.10 mg/kg at the end of surgery.

In post-operative care unit (PACU), patient is connected immediately to PCA morphine with the following protocol is used: bolus 1mg, lock-out 5 minutes, no basal infusion, and 4 hours limit is set at 20 mg. Rescue analgesia is provided by intravenous Fentanyl 0.5mcg/kg each bolus if required in PACU.

Post-operation, patient will continue to receive PCA Morphine (for the next 48 hours) in the ward and regular intravenous Paracetamol 15mg/kg 6 hourly (for the first 24 hours; subsequently change to oral Paracetamol) up to hospital discharge.
Intervention code [1] 297993 0
Treatment: Drugs
Comparator / control treatment
The patient will then receive a single dose of placebo preoperatively. In the ward, further 4 more doses of placebo will be served 12 hourly at post-operation 12 hours, 24 hours, 36 hours and 48 hours post-operatively.

THe placebo drug contain malto dextrin
Control group
Placebo

Outcomes
Primary outcome [1] 302023 0
To assess the post-operative pain control between treatment group and placebo group, as judged by the differences in mean total morphine consumption at the end of 48 hours post-operatively and the mean Visual Analogue Scale (VAS) score or Numeric Rating Scale (NRS) between treatment group and placebo group (composite of VAS and NRS).,
Timepoint [1] 302023 0
On the day of admission, pre-operation (one hour after drug administration); post operation 0 hour at PACU, post-operation 4 hours; 8 hours; 12 hours; 24 hours; 48 hours; and 72 hours in the ward.
Secondary outcome [1] 334524 0
To assess the anxiety score of patients between treatment group and placebo group as judged by the differences in Visual Analogue Scale for Anxiety (VAS-A),
Timepoint [1] 334524 0
On the day of admission, pre-operation (one hour after drug administration); post-operation 4 hours; 8 hours; 12 hours; 24 hours; 48 hours; and 72 hours in the ward.
Secondary outcome [2] 334525 0
To determine the adverse events i.e. incidence of nausea, vomiting, sedation, headache, dizziness, visual disturbances and dry mouth between both groups. The adverse events stated will by documented in a date collection sheets provided to the participants for self reporting.
Timepoint [2] 334525 0
Post operation 0 hour at PACU, post-operation 4 hours; 8 hours; 12 hours; 24 hours; 48 hours; and 72 hours in the ward.
Secondary outcome [3] 334526 0
To determine the incidence of neuropathic pain after surgery using painDETECT questionnaire by phone call.
Timepoint [3] 334526 0
2 weeks, 1 month and 6 months post operation.
Secondary outcome [4] 335321 0
To assess the anxiety score of patients between treatment group and placebo group as judged by the differences in Hospital Anxiety and Depression Score (HADS)
Timepoint [4] 335321 0
On the day of admission, pre-operation (one hour after drug administration); post operation 24 hours; 48 hours; and 72 hours in the ward.
Secondary outcome [5] 335322 0
To assess the anxiety score of patients between treatment group and placebo group as judged by the differences in Richmond Agitation and Sedation Scale (RASS).
Timepoint [5] 335322 0
On the day of admission, pre-operation (one hour after drug administration); post operation 0 hour at PACU, post-operation 4 hours; 8 hours; 12 hours; 24 hours; 48 hours; and 72 hours in the ward.

Eligibility
Key inclusion criteria
1. Patients who will be undergo elective single-staged idiopathic scoliosis surgery in University Malaya Medical Centre, Federal Territory, Malaysia between May 2017 and May 2019
2. American Society of Anesthesiologists (ASA) physical status I and II
Minimum age
10 Years
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Communication barrier
2. Patients on long term opioids, sedatives or anticonvulsants treatment pre-operatively
3. Known allergy to pregabalin or morphine
4. Diabetes mellitus of any type
5. Impaired renal function
6. Unable to use/ operate a patient controlled analgesic (PCA) device

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)
Placebo capsule will be specially manufactured by an appointed GMP certified laboratory and is identical to the original drug.

Central randomisation by computer. Allocation schedule will be obtained from an internet random number generator.

On the day of operation, a non-relevant personnel (scrub nurse, anaesthetic assistant etc.) will identify the allocation group following the above schedule one hour prior to the surgery. Thereafter, she or he will hand the assigned drug or placebo to the anaesthetic team in a sealed opaque envelope. All the members in the surgical team and anaesthetic team are blinded and unaware of the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A web-based random-number generator will be used to formulate an allocation schedule, from www.randomization.com created on 3/5/2017,
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
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
All data will be analyzed using SPSS software version 22 (Chicago, IL, USA). Variables with normal distribution were expressed as mean +/- standard deviation and compared with the parametric Unpaired Two-tailed t test. Data with skewed distribution were compared with the Mann-Whitney U test and expressed as median [Interquartile Range]. Categorical data was presented as frequencies (percentages) and compared with the chi-square test. Level of significance is set at p < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2017
Actual
Date of last participant enrolment
Anticipated
31/05/2019
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
68
Accrual to date
Final
Recruitment outside Australia
Country [1] 8885 0
Malaysia
State/province [1] 8885 0
Kuala Lumpur

Funding & Sponsors
Funding source category [1] 295738 0
Self funded/Unfunded
Name [1] 295738 0
Country [1] 295738 0
Primary sponsor type
Individual
Name
Associate Professor Dr. Mohd Shahnaz Hasan
Address
Department of Anaesthesiology,
Level 3,
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country
Malaysia
Secondary sponsor category [1] 295319 0
Individual
Name [1] 295319 0
Dr. Ng Ching Choe
Address [1] 295319 0
Department of Anaesthesiology,
Level 3,
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Malaysia
Country [1] 295319 0
Malaysia
Secondary sponsor category [2] 295320 0
Individual
Name [2] 295320 0
Dr. Yip Hing Wa
Address [2] 295320 0
Department of Anaesthesiology,
Level 3,
Faculty of Medicine,
University Malaya
50603 kuala Lumpur
Country [2] 295320 0
Malaysia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297040 0
Medical Research Ethics Committee, University of Malaya Medical Centre
Ethics committee address [1] 297040 0
University Malaya Medical Centre
Lembah Pantai
59100 Kuala Lumpur
Malaysia
Ethics committee country [1] 297040 0
Malaysia
Date submitted for ethics approval [1] 297040 0
02/11/2016
Approval date [1] 297040 0
07/02/2017
Ethics approval number [1] 297040 0
MREC ID NO: 2016112­-4486

Summary
Brief summary
Scoliosis surgery is a major operative procedure and is often linked with severe post-operative pain. Opioids administered either intravenously, subcutaneously, intrathecally or via epidural route are the mainstay for management of acute post-operative pain after scoliosis surgery. However, opioids administration regardless of route is associated with adverse effects such as post-operative nausea and vomiting (PONV), sedation, dry mouth, pruritus, and respiratory depression, all of which are undesirable in the post-operative period. Furthermore, use of opioids alone does not totally abort acute post-operative pain after scoliosis surgery.

Therefore, emphasis has been placed on concept of multimodal analgesia, where non-opioids are used in conjunction with opioids in an effort to reduce opioids use, and thus reduce its side effect. This approach also improves pain control due to different sites and mechanisms of pain modulation. Traditionally, non-opioids used are systemic Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), systemic Cyclo-Oxygenase-2 (COX-2) inhibitors, and local anaesthetics infiltration at operative site. Recently, anti-neuropathics such as gabapentin and pregabalin, both of which are a2d receptor modulators and are commonly used in chronic pain syndrome, have also been shown to be efficacious in controlling acute post-operative pain in a variety of surgeries. Common side effect of oral pregabalin includes sedation, dizziness, visual disturbances, dry mouth, and headache. In paediatric age group, pregabalin has been prescribed for neuropathic pain, epilepsy and dysautonomic crisis.

In terms of spine surgery, efficacy of pregabalin has been focused on lumbar discectomy, laminectomy or spinal fusion, which involves only 1-3 spinal segments. Use of pregabalin in scoliosis, often involving more spinal segments, has not been determined.

As standard practice in University Malaya Medical Center (UMMC), all patients undergoing corrective scoliosis surgery will receive patient controlled analgesia (PCA) morphine and oral paracetamol 15mg/kg 6 hourly after surgery. Based on our experience this group of patients still complained of pain on discharge home. Therefore in this research we aim to establish the efficacy of perioperative pregabalin as adjunct for post operative pain control in this group of patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72778 0
A/Prof Mohd Shahnaz Hasan
Address 72778 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Country 72778 0
Malaysia
Phone 72778 0
+60379493116
Fax 72778 0
Email 72778 0
shahnaz@ummc.edu.my
Contact person for public queries
Name 72779 0
A/Prof Mohd Shahnaz Hasan
Address 72779 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Country 72779 0
Malaysia
Phone 72779 0
+60379493116
Fax 72779 0
Email 72779 0
shahnaz@ummc.edu.my
Contact person for scientific queries
Name 72780 0
Dr Yip Hing Wa
Address 72780 0
Department of Anaesthesiology,
Level 3
Faculty of Medicine
University Malaya
50603 Kuala Lumpur
Country 72780 0
Malaysia
Phone 72780 0
+60379493116
Fax 72780 0
Email 72780 0
hwyip@ummc.edu.my

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