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Medrol Dosepak Taper for Delayed Post-op Recovery After TKA

Methylprednisolone Taper to Treat Delayed Post-Operative Recovery After Total Knee Arthroplasty: a Double-Blind Randomized Controlled Trial

Status
Terminated
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05113901
Enrollment
4
Registered
2021-11-09
Start date
2022-03-03
Completion date
2022-07-25
Last updated
2023-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Total Knee Arthroplasty

Keywords

Methylprednisolone, Delayed recover, range of motion

Brief summary

To evaluate the efficacy of a methylprednisolone taper on patients with decreased range of motion (ROM) or delayed recovery in the acute postoperative period following total knee arthroplasty (TKA). Patients with decreased ROM or delayed recovery six weeks to three months post-TKA will improve ROM and patient-reported outcomes at two weeks post-treatment initiation of methylprednisolone taper, as compared to similar patients who receive a placebo taper.

Detailed description

Total knee arthroplasty (TKA) is one of the most performed and efficacious orthopaedic procedures, with an estimated 7 million people living with a total knee prosthesis in 2010.1 The number of annual TKAs is predicted to increase by 85% by 2030 and 143% by 2050, equating to 1.26 million2 and 1.5 million3 procedures per year, respectively. In recent studies, knee prostheses have demonstrated their efficacy in 10-, 20-, and 25-year survival rates of 96.1%, 89.7%4, and 82.3%5, respectively. Similarly, comparing functional and patient-reported outcomes before and after surgery have confirmed the high success rate achieved with this procedure.6-10 However, recovery following total knee arthroplasty (TKA) in the acute postoperative period is variable. Most clinical improvements are achieved within the first three months postoperatively but can continue up to one year.11 There is currently a paucity of data evaluating the efficacy of oral corticosteroids in the six-week to three-month postoperative period in slowly recovering patients. Few treatments have been studied for patients who fail to achieve early range of motion or pain reduction milestones in the perioperative period. Periarticular and systemic corticosteroids improve pain and function in the immediate postoperative period, without an increase in adverse events.12-16 Additional doses of corticosteroids administered at 24 and 48 hours postoperatively have demonstrated greater improvements in pain and ROM compared to perioperative administration, with no difference in complication rates.17-20 However, few studies have evaluated the use of oral corticosteroids within a multimodal pain management regimen. Gardiner et al. evaluated low-dose steroids 10 days immediately following lumbar laminectomy and/or discectomy, in addition to a standard opioid regimen, and reported decreased subjective pain scores.21 Gottshalk et al. reported decreased patient reported pain from postoperative days 4-7 in early published results of a randomized controlled trial investigating administration of a methylprednisolone taper immediately following distal radius repair.22 Importantly, the current literature demonstrates low- and short-dose corticosteroids are safe.23 Intraoperative corticosteroids have been shown to improve pain and function in the acute postoperative period, and additional doses in the immediate postoperative period can potentiate and prolong this beneficiary effect, without increasing adverse events. Therefore, a methylprednisolone taper six weeks post-TKA may benefit patients experiencing decreased ROM or delayed recovery, including residual pain. Following TKA, care is taken to control pain, swelling, and stiffness, all of which may contribute to delayed recovery. For instance, more than 20% of TKA patients develop postoperative stiffness,24 known as arthrofibrosis, accounting for an estimated 28% of 90-day hospital readmissions.25 In treating patients with delayed recovery, corticosteroids are of particular interest because of its potent anti-inflammatory effect, evidenced by its ability to decrease postoperative levels of IL-6 and CRP.15 Corticosteroids block prostaglandin synthesis, which is responsible for sensitizing nociceptive pain receptors, and reduce vascular permeability, which causes edema following surgery.26, 27 Therefore, by reducing pain and edema, corticosteroids may allow for more effective physical therapy sessions and more rapid improvement in ROM and recovery following TKA. To the best of our knowledge, this is the first study to investigate the utility of a methylprednisolone taper six weeks to three months postoperatively following TKA. The authors present a double-blinded, randomized-controlled trial evaluating the role of a methylprednisolone taper on patients with decreased ROM or delayed recovery in the acute postoperative period.

Interventions

DRUGMethylprednisolone

21 x 4mg tablets at 6 weeks, qualifying for MUA if ROM \<90° at 8 weeks

DRUGPlacebo

21 sugar tablets at 6 weeks with standard management, qualifying for MUA if ROM \<90° at 8 weeks

Sponsors

Rush University Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* Any patient undergoing primary TKA with a diagnosis of osteoarthritis * ≥ 18 years old * ROM \<90° by 3 weeks postoperatively without improvement to \>90° by 6 weeks * Requiring a 30-pill oxycodone refill * NSAID allergy * Thigh circumference discrepancy \>2cm between legs from 3 to 6 weeks * Defense and Veterans Pain Rating Scale (DVPRS) \> 5 between 3 and 6 weeks * Willingness to undergo randomization

Exclusion criteria

* Reported chronic corticosteroid or opiate use * Suspected or confirmed periprosthetic joint infection * Revision TKA * Primary diagnosis other than osteoarthritis, including avascular necrosis, fracture, or post-traumatic arthritis * American Society of Anesthesiologists (ASA) score ≥ 4 * Reported history of liver or renal disease * Uncontrolled diabetes * Immunosuppression * ≤ 18 years old * Inability to take oral medications * Unable to provide consent

Design outcomes

Primary

MeasureTime frameDescription
Range of Motion in Degrees at Pre and Post TreatmentBaseline, Week 6 Following TreatmentRange of motion (ROM) from pre-treatment to six weeks following treatment. Patients started treatment after total knee replacement surgery and presented to clinic with at least one inclusion criteria to be enrolled. Range of motion in degrees is taken at each visit by a clinician (standard of care), starting at zero degrees (straight leg) to about 135 degrees. The ROM was documented as part of consenting and enrollment into study. Subjects returned to the office at 6 weeks post treatment where ROM was performed in a clinic setting once again and documented. ROM is done using a goniometer by a clinician in each clinic. This study was terminated early, therefore of the 4 enrolled, zero were randomized to the placebo group. Only 1 of the four subjects completed the 6 weeks, however, ROM was captured on all as standard of care.

Secondary

MeasureTime frameDescription
Patient Reported Outcome Measures: Post Treatment Pain Scores (6 Weeks)6 weeks post treatmentUsing daily defense and veterans pain rating scale (DVPRS) on a scale of 1 to 10, 10 being the worst. Please note, only one patient made it to the 6 week post treatment mark of the 4 enrolled. The study was terminated and none of the patients were randomized to the placebo group. All other patients followed up but were not interested in continuing. No range could be provided given only one subject answered and completed this visit
Patient Reported Outcome Measures: Pre Treatment Pain Scores Using Knee Society Scorespre treatmentKnee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee \*\*Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group.
Patient Reported Outcome Measures: Post Treatment Pain Scores3 weeks post treatmentKnee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee. \*\*Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. At 3 weeks post treatment, only 3 of the 4 subjects enrolled were still part of the study.
Patient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDays 1 through 6 following treatmentUsing Daily Visual Analogue Scale (VAS) pain score, which measures intensity of pain on a scale of 0 (no pain) to 10 (worst pain possible). \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.
Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatmentpre treatmentKnee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), a survey given to patients standard of care containing 7 questions. The score ranges from 0 to 100 where zero represents total disability and 100 represents a perfect knee health.
Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatmentpre treatmentForgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome.
Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment6 weeks after treatmentVR-12: Assesses physical functioning, physical/ mental limitations. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome.
Patient Reported Outcome Measures: Overall Assessment of Knee 6 Wks After Treatment6 weeks after treatmentForgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome.
Number of Participants With Complications Following Treatmentwithin 90 days after initial total knee arthroplastyManipulations under anesthesia (MUAs) following total knee arthroplasty surgery and treatment
Adverse Events or Outcomes Outside of Manipulations Under Anesthesiawithin 90 days after initial total knee arthroplastyAdverse outcomes including infection, avascular necrosis, and 90-day readmission rates
Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatmentpre treatmentVeterans Rand 12-Item Health Survey (VR-12), a survey of 12 questions to measure health relating to patient's quality of life. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome.

Countries

United States

Participant flow

Participants by arm

ArmCount
Methylprednisolone Taper
21 x 4mg tablets at 6 weeks, qualifying for MUA if ROM \<90° at 8 weeks Methylprednisolone: 21 x 4mg tablets at 6 weeks, qualifying for MUA if ROM \<90° at 8 weeks
4
Placebo Taper
21 sugar tablets at 6 weeks with standard management, qualifying for MUA if ROM \<90° at 8 weeks Placebo: 21 sugar tablets at 6 weeks with standard management, qualifying for MUA if ROM \<90° at 8 weeks
0
Total4

Baseline characteristics

CharacteristicPlacebo TaperTotalMethylprednisolone Taper
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants1 Participants1 Participants
Age, Categorical
Between 18 and 65 years
0 Participants3 Participants3 Participants
Age, Continuous63.31 years63.31 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants1 Participants1 Participants
Race (NIH/OMB)
White
0 Participants3 Participants3 Participants
Region of Enrollment
United States
4 participants4 participants
Sex: Female, Male
Female
0 Participants2 Participants2 Participants
Sex: Female, Male
Male
0 Participants2 Participants2 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 40 / 0
other
Total, other adverse events
0 / 40 / 0
serious
Total, serious adverse events
0 / 40 / 0

Outcome results

Primary

Range of Motion in Degrees at Pre and Post Treatment

Range of motion (ROM) from pre-treatment to six weeks following treatment. Patients started treatment after total knee replacement surgery and presented to clinic with at least one inclusion criteria to be enrolled. Range of motion in degrees is taken at each visit by a clinician (standard of care), starting at zero degrees (straight leg) to about 135 degrees. The ROM was documented as part of consenting and enrollment into study. Subjects returned to the office at 6 weeks post treatment where ROM was performed in a clinic setting once again and documented. ROM is done using a goniometer by a clinician in each clinic. This study was terminated early, therefore of the 4 enrolled, zero were randomized to the placebo group. Only 1 of the four subjects completed the 6 weeks, however, ROM was captured on all as standard of care.

Time frame: Baseline, Week 6 Following Treatment

Population: \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

ArmMeasureGroupValue (MEAN)
Methylprednisolone TaperRange of Motion in Degrees at Pre and Post TreatmentPre treatment82.5 Range of Motion in Degrees
Methylprednisolone TaperRange of Motion in Degrees at Pre and Post TreatmentPost treatment112 Range of Motion in Degrees
Secondary

Adverse Events or Outcomes Outside of Manipulations Under Anesthesia

Adverse outcomes including infection, avascular necrosis, and 90-day readmission rates

Time frame: within 90 days after initial total knee arthroplasty

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Methylprednisolone TaperAdverse Events or Outcomes Outside of Manipulations Under Anesthesia0 Participants
Placebo TaperAdverse Events or Outcomes Outside of Manipulations Under Anesthesia0 Participants
Secondary

Number of Participants With Complications Following Treatment

Manipulations under anesthesia (MUAs) following total knee arthroplasty surgery and treatment

Time frame: within 90 days after initial total knee arthroplasty

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Methylprednisolone TaperNumber of Participants With Complications Following Treatment0 Participants
Placebo TaperNumber of Participants With Complications Following Treatment0 Participants
Secondary

Patient Reported Outcome Measures:(Immediate) Post Treatment Pain Scores

Using Daily Visual Analogue Scale (VAS) pain score, which measures intensity of pain on a scale of 0 (no pain) to 10 (worst pain possible). \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

Time frame: Days 1 through 6 following treatment

Population: \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

ArmMeasureGroupValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 12.33 score on a scale
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 23 score on a scale
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 31.33 score on a scale
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 41.33 score on a scale
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 51.67 score on a scale
Methylprednisolone TaperPatient Reported Outcome Measures:(Immediate) Post Treatment Pain ScoresDay 62.3 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment

UCLA activity score, on a scale of 1 to 10 where 10 is the most active patient with examples of activities

Time frame: 6 weeks after treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment5.25 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment

VR-12: Assesses physical functioning, physical/ mental limitations. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome.

Time frame: 6 weeks after treatment

Population: This study was terminated early after only 4 subjects were enrolled. None of these patients were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment50.28 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment

Single Assessment Numeric Evaluation (SANE), a single-question patient rating of 0-100, scoring their function to the area being treated. Zero represents a poor functional knee and 100 is the best functioning.

Time frame: 6 weeks after treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment89.5 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee 6 Wks After Treatment

Forgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome.

Time frame: 6 weeks after treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee 6 Wks After Treatment57.82 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment

Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), a survey given to patients standard of care containing 7 questions. The score ranges from 0 to 100 where zero represents total disability and 100 represents a perfect knee health.

Time frame: 6 weeks after treatment

Population: Please note, this study was terminated early where we only enrolled 4 subjects. Of the 4, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment72.12 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment

Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), a survey given to patients standard of care containing 7 questions. The score ranges from 0 to 100 where zero represents total disability and 100 represents a perfect knee health.

Time frame: pre treatment

Population: Please note, the study was terminated early and only 4 patients were enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment50.04 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment

Single Assessment Numeric Evaluation (SANE), a single-question patient rating of 0-100, scoring their function to the area being treated. Zero represents a poor functional knee and 100 is the best functioning.

Time frame: pre treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee Before Treatment29.5 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment

Veterans Rand 12-Item Health Survey (VR-12), a survey of 12 questions to measure health relating to patient's quality of life. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome.

Time frame: pre treatment

Population: Please note, this study was terminated early where we only enrolled 4 subjects. Of the 4, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee Before Treatment38.73 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment

Forgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome.

Time frame: pre treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment91.67 score on a scale
Secondary

Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment

UCLA activity score, on a scale of 1 to 10 where 10 is the most active patient with examples of activities

Time frame: pre treatment

Population: Please note, this study was terminated early with only 4 patients enrolled. Of the 4 enrolled, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment4.25 score on a scale
Secondary

Patient Reported Outcome Measures: Post Treatment Pain Scores

Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee. \*\*Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. At 3 weeks post treatment, only 3 of the 4 subjects enrolled were still part of the study.

Time frame: 3 weeks post treatment

Population: \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Post Treatment Pain Scores68.33 score on a scale
Secondary

Patient Reported Outcome Measures: Post Treatment Pain Scores

Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee. \*\*Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. This is a standard of care survey available on all subjects.

Time frame: 6 weeks post treatment

Population: \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Post Treatment Pain Scores78.75 score on a scale
Secondary

Patient Reported Outcome Measures: Post Treatment Pain Scores (6 Weeks)

Using daily defense and veterans pain rating scale (DVPRS) on a scale of 1 to 10, 10 being the worst. Please note, only one patient made it to the 6 week post treatment mark of the 4 enrolled. The study was terminated and none of the patients were randomized to the placebo group. All other patients followed up but were not interested in continuing. No range could be provided given only one subject answered and completed this visit

Time frame: 6 weeks post treatment

Population: This study was terminated early, only 1 of the 4 enrolled subjects reached the 6 week mark.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Post Treatment Pain Scores (6 Weeks)1.93 score on a scale
Secondary

Patient Reported Outcome Measures: Pre Treatment Pain Scores Using Knee Society Scores

Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee \*\*Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group.

Time frame: pre treatment

Population: \*\*Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group.

ArmMeasureValue (MEAN)
Methylprednisolone TaperPatient Reported Outcome Measures: Pre Treatment Pain Scores Using Knee Society Scores66.25 score on a scale

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026