Large Doses of Methylprednisolone Combined With Gabapentin in Total Knee Arthroplasty

Knee Osteoarthritis Clinical Trial

Official title:

The Impact of Pre-emptive Large Doses of Methylprednisolone Combined With Gabapentin on Pain Treatment and Convalescence After Total Knee Arthroplasty in Elderly: A Double-blind Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04653415
• Other study ID #: 1072.6120.11.2020
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2019
• Est. completion date: May 1, 2020

Study information

• Verified date: November 2020
• Source: Jagiellonian University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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).170 patients operated on due to unilateral TKA will be double-blinded randomized into two groups: the study and the controls. Exclusion criteria are: clinical situation that 1/ restricted glucocorticoid administration: diabetes type 1 and 2, CRP levels above normal values (≥5 mg/l), chronic steroid treatment, peptic ulcers treated in the past 30 days and 2/and the chronic pain in the course of gonarthrosis, high intensity requiring use opioids.

The participants of the study will be subjected to the standardized procedure of subarachnoid anesthesia with subsequent unilateral femoral nerve block at the operated side, followed by the surgical procedure - unilateral TKA. 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. Prior to anesthesia induction, the patients receive: anti-infection prophylactics intravenous cephazolin 2.0 g, for hemostasis control - tranexamic acid 1.0 g, an anti-emetic agent - ondansetron 8 mg. Fluid supply (crystalloids) will be standardized: 12 ml/kg in the first hour of surgery and 6 ml/kg in the following hours, packed red blood cells if blood loss exceeded 600 ml and hemoglobin concentration <10g/l during the time of operation. Pain management will be carried out based on the results of the NRS scales at rest. Every 6 hours NRS will be checked and intravenous PCA (patient-controlled analgesia) oxycodone hydrochloride, if pain was ≥4 points NRS or intravenous paracetamol, metamizole, if the pain was 2 - 4 NRS points will be administered, all pain medications will be calculated for 1 kg of body weight. In keeping with the ERAS (Enhanced Recovery After Surgery) protocol, on the day of surgery the patients will receive orally fluids and meals, will be mobilized and rehabilitated.

The study was approved by the institutional review board (nr 1072.6120.11.2020). Oral and written informed consent to participate in the study will be collected from all participants of the study. The statistical analysis of the groups will be performed to asess the demographic dates, life parameters, general condition in keeping with the ASA (American Society of Anesthesiology), POSSUM (Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity) score, total dose of analgesic medications administered parenterally calculated for 1 kg of body mass in response to value of NRS at rest on day 0, time of administration the first dose, and duration of peripheral nerve block. On the day of surgery and on subsequent days, determinations will be made of glycemia levels and inflammatory markers: C-reactive protein (CRP) and leukocytosis levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: May 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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,

Related Conditions & MeSH terms

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

Intervention

Drug:
• Gabapentin 300mg
The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.
• Methylprednisolone 125 mg
The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.
• Tablet
The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution
• Normal Saline 10 mL Injection
The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution

Locations

Country	Name	City	State
Poland	University Hospital in Krakow	Krakow	Malopolska

Sponsors (1)

Lead Sponsor	Collaborator
Jagiellonian University

Country where clinical trial is conducted

Poland, 

References & Publications (15)

Berg U, BüLow 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. — View Citation

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. 2020 Sep 17. doi: 10.1007/s00264-020-04802-8. [Epub ahead of print] — View Citation

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. — View Citation

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. Review. — View Citation

Jørgensen 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean age	Mean age in years	the day of surgery
Other	Mean hospitalization time	Mean hospitalization time in days	from admission to hospital till 14 days after surgery
Other	Mean postoperative hospitalization time	Mean postoperative hospitalization time in days	change from 0 till 14 days after surgery
Other	Postoperative Mean Arterial Pressure (MAP)	Postoperative Mean Arterial Pressure (MAP) measured in mmHg	change in 0,1,2,3 days after surgery
Other	Postoperative pulse	Postoperative pulse (x/min)) measured in x/min	change in 0,1,2,3 days after surgery
Other	Postoperative saturation (Sp02) of the arterial blood	Postoperative saturation (Sp02) of the arterial blood measured in %	change in 0,1,2,3 days after surgery
Other	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) morbidity	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) morbidity measured in %	the day of the surgery
Other	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) mortality	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) mortality measured in %	the day of the surgery
Other	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score	Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score measured in points (minimum 12, maximum 96)	the day of the surgery
Other	American Society of Anesthesiology Score (ASA)	American Society of Anesthesiology Score (ASA), grade I-IV	the day of the surgery
Primary	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
Primary	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
Primary	C-reactive protein (CRP) level	C-reactive protein (CRP) level measured in mg/l	change in 0,1,2,3 days after surgery
Primary	Leukocytosis level	Leukocytosis level measured in µL	change in 0,1,2,3 days after surgery
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Duration of femoral nerve blockade	The time of femoral nerve block	on the day of surgery
Secondary	Blood glucose level	The level of glucose in blood in mmol/l	change in 0,1,2,3 days after surgery