Large Doses of Methylprednisolone Combined With Gabapentin in Total Knee Arthroplasty

NCT04653415 | Completed Phase 4 DMC

• 1 other identifier: 1072.6120.11.2020
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study was to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). For the study investigators will qualify one hundred seventy, above 65 years old patients. The participants will be double-blind randomized into two groups: the study and controls The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone, while the others placebo. Perioperatively, all the patients will receive opioid and nonopioid analgesic agents calculated for 1 kg of body weight. Investigators will measure the levels of inflammatory markers (leukocytosis, C-reactive protein - CRP), pain intensity level at rest (numerical rating scale - NRS), the life parameters and all complications.

Conditions

Arthroplasty Complications; Knee Osteoarthritis; Pain, Postoperative; Perioperative Complication

Keywords

total knee arthroplasty; pre-emptive analgesia; methylprednisolone; gabapentin; opioid dose; pain intensity; infection rate

Outcome Measures

Primary Outcomes (9)

• Pain intensity assessed by NRS

  The level of postoperative pain measured in the numerical rating scale (NRS) at rest (minimum 0 - no pain, maximum 10 - the maximum of pain).

  change in every 6 hours on day 0

• the dose of parenteral analgesics agents

  Dose of oxycodone hydrochloride in mg/kg body weight, paracetamol in mg/kg body weight, metamizole in g/kg body weight

  24 hours

• C-reactive protein (CRP) level

  C-reactive protein (CRP) level measured in mg/l

  change in 0,1,2,3 days after surgery

• Leukocytosis level

  Leukocytosis level measured in µL

  change in 0,1,2,3 days after surgery

• Adverse effects

  The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

  0 day after surgery

• Adverse effects

  The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

  1 day after surgery

• Adverse effects

  The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

  2 day after surgery

• Adverse effects

  The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

  3 day after surgery

• Adverse effects

  The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

  14 day after surgery

Secondary Outcomes (2)

• Duration of femoral nerve blockade

  on the day of surgery

• Blood glucose level

  change in 0,1,2,3 days after surgery

Other Outcomes (10)

• Mean age

  the day of surgery

• Mean hospitalization time

  from admission to hospital till 14 days after surgery

• Mean postoperative hospitalization time

  change from 0 till 14 days after surgery

Study Arms (2)

Study Group

ACTIVE COMPARATOR

The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.

Drug: Gabapentin 300mg; Drug: Methylprednisolone 125 mg

Controls group

PLACEBO COMPARATOR

The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - saline solution.

Drug: Tablet; Drug: Normal Saline 10 mL Injection

Interventions

Gabapentin 300mg DRUG

The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.

Study Group

Methylprednisolone 125 mg DRUG

The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.

Study Group

Tablet DRUG

The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution

Controls group

Normal Saline 10 mL Injection DRUG

The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution

Controls group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• patients over 65 years old operated on unilateral total knee arthroplasty

You may not qualify if:

• diabetes type 1 and 2,
• CRP levels above normal values (≥5 mg/l),
• chronic steroid treatment,
• peptic ulcers treated in the past 30 days,
• chronic pain in the course of gonarthrosis,

Sponsors & Collaborators

• Jagiellonian University: lead

Study Sites (1)

University Hospital in Krakow

Krakow, Malopolska, 30688, Poland

Location

Related Publications (15)

• Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.

  PMID: 23392233 BACKGROUND

• Lamplot JD, Wagner ER, Manning DW. Multimodal pain management in total knee arthroplasty: a prospective randomized controlled trial. J Arthroplasty. 2014 Feb;29(2):329-34. doi: 10.1016/j.arth.2013.06.005. Epub 2013 Jul 11.

  PMID: 23850410 BACKGROUND

• Kehlet H, Lindberg-Larsen V. High-dose glucocorticoid before hip and knee arthroplasty: To use or not to use-that's the question. Acta Orthop. 2018 Oct;89(5):477-479. doi: 10.1080/17453674.2018.1475177. Epub 2018 May 21. No abstract available.

  PMID: 29781366 BACKGROUND

• Luna IE, Kehlet H, Petersen MA, Aasvang EK. Clinical, nociceptive and psychological profiling to predict acute pain after total knee arthroplasty. Acta Anaesthesiol Scand. 2017 Jul;61(6):676-687. doi: 10.1111/aas.12899. Epub 2017 May 16.

  PMID: 28508511 BACKGROUND

• Jorgensen CC, Pitter FT, Kehlet H; Lundbeck Foundation Center for Fast-track Hip and Knee Replacement Collaborative Group. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement. Br J Anaesth. 2017 Aug 1;119(2):267-275. doi: 10.1093/bja/aex190.

  PMID: 28854533 BACKGROUND

• Hartman J, Khanna V, Habib A, Farrokhyar F, Memon M, Adili A. Perioperative systemic glucocorticoids in total hip and knee arthroplasty: A systematic review of outcomes. J Orthop. 2017 Apr 12;14(2):294-301. doi: 10.1016/j.jor.2017.03.012. eCollection 2017 Jun.

  PMID: 28442852 BACKGROUND

• Lindberg-Larsen V, Ostrowski SR, Lindberg-Larsen M, Rovsing ML, Johansson PI, Kehlet H. The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial. Anaesthesia. 2017 Oct;72(10):1217-1224. doi: 10.1111/anae.13983. Epub 2017 Jul 26.

  PMID: 28744857 BACKGROUND

• Gadek A, Liszka H, Zajac M. The effect of pre-operative high doses of methylprednisolone on pain management and convalescence after total hip replacement in elderly: a double-blind randomized study. Int Orthop. 2021 Apr;45(4):857-863. doi: 10.1007/s00264-020-04802-8. Epub 2020 Sep 17.

  PMID: 32940751 BACKGROUND

• Lee JK, Chung KS, Choi CH. The effect of a single dose of preemptive pregabalin administered with COX-2 inhibitor: a trial in total knee arthroplasty. J Arthroplasty. 2015 Jan;30(1):38-42. doi: 10.1016/j.arth.2014.04.004. Epub 2014 Apr 13.

  PMID: 24851793 BACKGROUND

• Lubis AMT, Rawung RBV, Tantri AR. Preemptive Analgesia in Total Knee Arthroplasty: Comparing the Effects of Single Dose Combining Celecoxib with Pregabalin and Repetition Dose Combining Celecoxib with Pregabalin: Double-Blind Controlled Clinical Trial. Pain Res Treat. 2018 Aug 7;2018:3807217. doi: 10.1155/2018/3807217. eCollection 2018.

  PMID: 30174951 BACKGROUND

• Osinski T, Bekka S, Regnaux JP, Fletcher D, Martinez V. Functional recovery after knee arthroplasty with regional analgesia: A systematic review and meta-analysis of randomised controlled trials. Eur J Anaesthesiol. 2019 Jun;36(6):418-426. doi: 10.1097/EJA.0000000000000983.

  PMID: 30950899 BACKGROUND

• Berg U, BuLow E, Sundberg M, Rolfson O. No increase in readmissions or adverse events after implementation of fast-track program in total hip and knee replacement at 8 Swedish hospitals: An observational before-and-after study of 14,148 total joint replacements 2011-2015. Acta Orthop. 2018 Oct;89(5):522-527. doi: 10.1080/17453674.2018.1492507. Epub 2018 Jul 9.

  PMID: 29985681 BACKGROUND

• Pamilo KJ, Torkki P, Peltola M, Pesola M, Remes V, Paloneva J. Fast-tracking for total knee replacement reduces use of institutional care without compromising quality. Acta Orthop. 2018 Apr;89(2):184-189. doi: 10.1080/17453674.2017.1399643. Epub 2017 Nov 21.

  PMID: 29160123 BACKGROUND

• Shen S, Gao Z, Liu J. The efficacy and safety of methylprednisolone for pain control after total knee arthroplasty: A meta-analysis of randomized controlled trials. Int J Surg. 2018 Sep;57:91-100. doi: 10.1016/j.ijsu.2018.07.009. Epub 2018 Aug 16.

  PMID: 30120990 BACKGROUND

• Lei Y, Xie J, Xu B, Xie X, Huang Q, Pei F. The efficacy and safety of multiple-dose intravenous tranexamic acid on blood loss following total knee arthroplasty: a randomized controlled trial. Int Orthop. 2017 Oct;41(10):2053-2059. doi: 10.1007/s00264-017-3519-x. Epub 2017 May 31.

  PMID: 28567578 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain, Postoperative; Pain

Interventions

Gabapentin; Methylprednisolone; Tablets; Saline Solution; Injections

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants of the study are blinded to receive methylprednisolone with gabapentin (the study group) or placebo (the controls group). Only nurse knows if administer drug or placebo. Both outcome assessor and investigator are blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principial Investigator, Assisstant Professor

Model Details: two groups: the study and controls

Study Record Dates

• First Submitted: November 21, 2020
• First Posted: December 4, 2020
• Study Start: June 1, 2019
• Primary Completion: January 1, 2020
• Study Completion: May 1, 2020
• Last Updated: December 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)