Large Doses of Methylprednisolone Combined With Gabapentin in Total Knee Arthroplasty

Sponsor

Jagiellonian University (Other)

Overall Status

Completed

CT.gov ID

NCT04653415

Collaborator

(none)

160

Enrollment

Location

Arms

Actual Duration (Months)

14.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arthroplasty Complications Knee Osteoarthritis Pain, Postoperative Perioperative Complication	Drug: Gabapentin 300mg Drug: Methylprednisolone 125 mg Drug: Tablet Drug: Normal Saline 10 mL Injection	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

two groups: the study and controlstwo groups: the study and controls

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 1, 2019

Actual Primary Completion Date :

Jan 1, 2020

Actual Study Completion Date :

May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Study Group 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 The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone. Drug: 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.
Placebo Comparator: Controls group The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - saline solution.	Drug: Tablet The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution Drug: Normal Saline 10 mL Injection The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution

Arm

Intervention/Treatment

Active Comparator: Study Group

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

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

Drug: 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.

Placebo Comparator: Controls group

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

Drug: Tablet

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

Drug: Normal Saline 10 mL Injection

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

Outcome Measures

Primary Outcome Measures

Pain intensity assessed by NRS [change in every 6 hours on day 0]
The level of postoperative pain measured in the numerical rating scale (NRS) at rest (minimum 0 - no pain, maximum 10 - the maximum of pain).
the dose of parenteral analgesics agents [24 hours]
Dose of oxycodone hydrochloride in mg/kg body weight, paracetamol in mg/kg body weight, metamizole in g/kg body weight
C-reactive protein (CRP) level [change in 0,1,2,3 days after surgery]
C-reactive protein (CRP) level measured in mg/l
Leukocytosis level [change in 0,1,2,3 days after surgery]
Leukocytosis level measured in µL
Adverse effects [0 day after surgery]
The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities
Adverse effects [1 day after surgery]
The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities
Adverse effects [2 day after surgery]
The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities
Adverse effects [3 day after surgery]
The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities
Adverse effects [14 day after surgery]
The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities

Secondary Outcome Measures

Duration of femoral nerve blockade [on the day of surgery]
The time of femoral nerve block
Blood glucose level [change in 0,1,2,3 days after surgery]
The level of glucose in blood in mmol/l

Other Outcome Measures

Mean age [the day of surgery]
Mean age in years
Mean hospitalization time [from admission to hospital till 14 days after surgery]
Mean hospitalization time in days
Mean postoperative hospitalization time [change from 0 till 14 days after surgery]
Mean postoperative hospitalization time in days
Postoperative Mean Arterial Pressure (MAP) [change in 0,1,2,3 days after surgery]
Postoperative Mean Arterial Pressure (MAP) measured in mmHg
Postoperative pulse [change in 0,1,2,3 days after surgery]
Postoperative pulse (x/min)) measured in x/min
Postoperative saturation (Sp02) of the arterial blood [change in 0,1,2,3 days after surgery]
Postoperative saturation (Sp02) of the arterial blood measured in %
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) morbidity [the day of the surgery]
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) morbidity measured in %
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) mortality [the day of the surgery]
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) mortality measured in %
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score [the day of the surgery]
Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score measured in points (minimum 12, maximum 96)
American Society of Anesthesiology Score (ASA) [the day of the surgery]
American Society of Anesthesiology Score (ASA), grade I-IV