Outcomes Of Perioperative Pregabalin On Total Knee Arthroplasty

Sponsor

National University Hospital, Singapore (Other)

Overall Status

Completed

CT.gov ID

NCT02954484

Collaborator

(none)

116

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to provide high quality evidence from a double-blinded, randomized controlled trial on the efficacy of perioperative pregabalin in reducing morphine requirements, improving pain scores and reducing chronic neuropathic pain when compared with placebo for primary total knee arthroplasty. It hence aims to improve on choice of analgesia adjuncts for total knee arthroplasty.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative	Drug: pregabalin Drug: Placebo Drug: Etoricoxib Drug: paracetamol Drug: Morphine Drug: Ropivacaine	Phase 3

Detailed Description

Aims:

Whether pregabalin given preoperatively and for one week postoperatively in addition to patient-controlled analgesia (PCA) morphine is effective in reducing morphine requirements, improving pain scores and reducing chronic neuropathic pain when compared with placebo for primary total knee arthroplasty.

Methodology:

A single-centre double-blind randomized controlled trial in patients undergoing primary total knee arthroplasty. All subjects receive PCA morphine, paracetamol 1g every six hours, etoricoxib 120mg once daily postoperatively. Subjects receive either pregabalin 75mg po preoperatively followed by 75mg OM and 25mg ON for two days postoperatively or matching placebo. The primary outcome is cumulative morphine consumption at 72 hr following surgery. Secondary outcome measures included pain scores, knee range of motion and patient satisfaction.

Study Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Outcomes Of Perioperative Pregabalin On Total Knee Arthroplasty: A Randomized Controlled Trial

Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PREGABALIN All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive pregabalin 75mg orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery.	Drug: pregabalin see arm/group description. Lyrica manufacture site: Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany. Other Names: Lyrica (Pfizer Pte Ltd, Singapore) Drug: Etoricoxib Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore Other Names: 'Arcoxia' Drug: paracetamol Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia Other Names: acetaminophen Drug: Morphine patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany Drug: Ropivacaine Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden Other Names: 'Naropin'
Placebo Comparator: PLACEBO All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive either placebo tablet (of identical appearance to pregabalin) orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery.	Drug: Placebo Placebo capsule containing lactose and MCC (no active ingredients). Other Names: Manufactured by Beacons Pharmaceuticals Pte Ltd, Singapore. Drug: Etoricoxib Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore Other Names: 'Arcoxia' Drug: paracetamol Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia Other Names: acetaminophen Drug: Morphine patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany Drug: Ropivacaine Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden Other Names: 'Naropin'

Arm

Intervention/Treatment

Active Comparator: PREGABALIN

All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive pregabalin 75mg orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery.

Drug: pregabalin

see arm/group description. Lyrica manufacture site: Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany.

Other Names:

Lyrica (Pfizer Pte Ltd, Singapore)

Drug: Etoricoxib

Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore

Other Names:

'Arcoxia'

Drug: paracetamol

Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia

Other Names:

acetaminophen

Drug: Morphine

patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany

Drug: Ropivacaine

Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden

Other Names:

'Naropin'

Placebo Comparator: PLACEBO

All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive either placebo tablet (of identical appearance to pregabalin) orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery.

Drug: Placebo

Placebo capsule containing lactose and MCC (no active ingredients).

Other Names:

Manufactured by Beacons Pharmaceuticals Pte Ltd, Singapore.

Drug: Etoricoxib

Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore

Other Names:

'Arcoxia'

Drug: paracetamol

Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia

Other Names:

acetaminophen

Drug: Morphine

patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany

Drug: Ropivacaine

Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden

Other Names:

'Naropin'

Outcome Measures

Primary Outcome Measures

Cumulative morphine consumption at 72 hours postoperatively [72 hours postoperatively]

Secondary Outcome Measures

Functional scores: SF-36v2 at 3 months and 6 months postoperatively [3 months and 6 months postoperatively]
Functional scores: Knee Society Score at 3 months and 6 months postoperatively [3 months and 6 months postoperatively]
Functional scores: WOMAC at 3 months and 6 months postoperatively [3 months and 6 months postoperatively]
Western Ontario and McMaster Universities Arthritis Index (WOMAC)
Knee range of motion at 3 months and 6 months postoperatively [3 months and 6 months postoperatively]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients undergoing primary total knee arthroplasty

Exclusion Criteria:

revision or bilateral arthroplasty, significant renal or hepatic impairment, documented allergy or intolerance to NSAIDs, paracetamol, morphine or pregabalin, chronic pain syndrome treated with chronic opioids, obstructive sleep apnea not treated with continuous positive airway pressure, seizures, breastfeeding, inability to use patient-controlled analgesia.