PainPhase 4NCT04082533
Intravenous (IV) Hydrocortisone for TKA (Total Knee Arthroplasty)
A Phase 4 study testing Hydrocortisone and Dextrose 5% in water (D5W) in people with Pain and Arthrofibrosis, run by Hospital for Special Surgery, New York at 1 site in United States.
Trial summary
In this study, total knee replacement patients will be determined to be stiff or non-stiff preoperatively. Stiffness designation is determined by preoperative range of motion (if flexion is < 100 degrees, or extension lag is > 10 degrees). Read more about this study
- Who is it for?
- Ages 18 to 83 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Arthrofibrosis, Osteoarthritis, Knee
- What is being tested?
- Hydrocortisone and Dextrose 5% in water (D5W)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2019to Jul 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 83 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Elective primary unilateral total knee arthroplasty
- Osteoarthritis (OA) within the affected joint
- Patients of surgeons who have agreed to participate in the study
- Age ≥18 to 83 years
- American Society of Anesthesiologists (ASA) Physical Status 1-3
- Neuraxial Anesthesia
- Adductor canal block (ACB), Interspace between the popliteal artery and capsule of the posterior knee (IPACK) block (unless valgus knee patient), and Periarticular Injection (PAI) for postoperative pain
Who cannot join
- Contraindication to regional anesthesia, non-steroidal anti-inflammatory drugs, or steroids
- Pre-operative oral steroid use in the past 3 months
- Body mass index (BMI) greater than or equal to 45
- Intraarticular steroid injections within two months of scheduled surgery in affected joint
- Non-English speaking
- Pre-existing diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, Type I diabetes)
Show all 15Show fewer
- Active infection
- History of >6 weeks of daily opioid use and/or any use of non-prescribed opioids within one year
- Pregnant women
- Previous study participants in this study
- Type II Diabetes on insulin
- History of refractory postoperative nausea and vomiting (PONV) or PONV after sedation (can include if nausea only after general anesthesia)
- Previous hardware in affected joint
- Open Reduction and Internal Fixation (ORIF) surgery to affected joint
- Cementless total knee arthroplasty (TKA)
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital for Special Surgery
New York, New York, 10021
About this study
Official title: Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study
In this study, total knee replacement patients will be determined to be stiff or non-stiff preoperatively. Stiffness designation is determined by preoperative range of motion (if flexion is < 100 degrees, or extension lag is > 10 degrees). The stiff and non-stiff groups will both be randomized to two groups to receive either intravenous hydrocortisone or a placebo at 3 intervals postoperatively. Patients will be followed up with in hospital and via the phone on postoperative day (POD) 1 and 2, as well as 6 weeks, 6 months, 1 year, and 2 years postoperatively. Patients will also have blood drawn preoperatively in the OR, on POD1, at their 6 week followup, and at their 1 and 2 year follow ups. This blood will be processed and analyzed.
Read the detailed description
TKA is the standard of care for treating patients suffering from end-stage knee arthritis and other disabling knee injuries. Indications have increased to ever younger patients and, combined with the aging US population, nearly 700,000 Americans receive TKAs each year. In spite of surgery, many patients experience persistent pain, stiffness or instability that negatively impacts their quality of life; up to 5% experience TKA failure in the first 10 years.
Presently, IV stress dose steroids is an accepted practice for bilateral knee replacement (BTKR) leading to decreased pain 24 hours after surgery and improved range of motion (ROM) on postoperative day 2 (POD2). These benefits are likely due to suppression of inflammation immediately after surgery. It is not clear if IV stress dose steroids improve ROM at later time points. Moreover, it is not clear if IV hydrocortisone improves clinical outcomes in unilateral TKA, where pain and joint stiffness remain significant challenges weeks after surgery. The investigators hypothesize that IV hydrocortisone will increase ROM at 6 weeks following surgery.
This study will enroll 132 patients that will be followed for up to 2 years. By integrating cell and molecular biology, biomechanics, and imaging technologies (including a CT scan at 1 year), this study is designed to comprehensively examine the long term effects of IV hydrocortisone on joint stiffness, pain, clinically relevant inflammatory states, and the synovium following unilateral TKA. Because subjects with variable ROMs will be enrolled in the study and followed over time, the findings may enable the development of biomarker prediction tools and the targeting of appropriate prevention and management measures for patients at highest risk of joint stiffness and subsequent surgical intervention.
- Conditions
- Pain, Arthrofibrosis, Osteoarthritis, Knee
- Being tested
- Hydrocortisone, Dextrose 5% in water (D5W)
- Keywords
- total knee replacement, hydrocortisone
- Medical subject headings
- Pain, Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Patients will be receiving 100 mg intravenous hydrocortisone every 8 hours, starting in the holding area roughly 2 hours prior to first incision.
Dextrose 5% in water (D5W)Drug
Also called Placebo
Patients will be receiving a matched volume of D5W every 8 hours, starting in the holding area roughly 2 hours prior to first incision.
| Study group | Role | What they receive |
|---|---|---|
| Stiffness Intravenous Hydrocortisone | Active comparator | Total knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. Receives: Drug: Hydrocortisone |
| Stiffness Intravenous Placebo | Placebo comparator | Total knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. Receives: Drug: Dextrose 5% in water (D5W) |
| Non-stiff Intravenous Hydrocortisone | Active comparator | Total knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. Receives: Drug: Hydrocortisone |
| Non-stiff Intravenous placebo | Placebo comparator | Total knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. Receives: Drug: Dextrose 5% in water (D5W) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative Range of Motion (ROM)
The primary outcome is range of motion at patients' 6 week (±2 weeks) postoperative surgeon appointment.
Measured: 6 weeks postoperative (±2 weeks)
Secondary outcomes (11)
Postoperative Stiffness
The rate of stiffness at the patients' 6 week postoperative surgeon appointment. Stiffness is defined as flexion < 100 degrees or extension lag > 10 degrees.
Measured: 6 weeks postoperative (±2 weeks)
Numeric Rating Scale (NRS)
Patient reported pain level on a scale from 0 (no pain at all) to 10 (worst pain imaginable).
Measured: baseline (preoperative), postoperative day (POD) 1, POD2, 6 weeks postop, 1 year postop, 2 years postop
PainDETECT Neuropathic Pain Score
Patient reported PainDETECT neuropathic pain scores. Scores from 0-12 indicate no neuropathic pain, 13-18 indicates unclear neuropathic pain, 19-38 indicates positive neuropathic pain. The PainDETECT questionnaire asks numerous questions regarding the type of pain patients are experiencing and answers are scored never (0), hardly noticed (1), slightly (2), moderately (3), strongly (4), and very strongly (5).
Measured: baseline (preoperative), 6 weeks postop, 1 year postop, 2 years postop
Opioid consumption
Patient reported opioid consumption information at pre-surgical screening appointment, in the holding area before surgery, on postoperative day 1, postoperative day 2, 6 weeks, 6 months, 1 year and 2 years postoperatively
Measured: pre-surgical screening (PSS and holding area), day of surgery (DOS), POD1, POD2 at 6 weeks, 6 months 1 year and 2 years postoperatively,
Knee injury and Osteoarthritis Outcome Score (KOOS Jr.)
Knee injury and Osteoarthritis Outcome Score (KOOS Jr.) scores measured at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The KOOS Jr. survey involves 7 questions scored from 0 to 4 for a total score of 0 to 28. A score of 0 correlates to complete loss of knee function, whereas 28 correlates to completely healthy knee function.
Measured: Preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Lower extremity Activity Survey (LEAS) scores
Lower extremity Activity Survey (LEAS) scores at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The LEAS contains 20 questions regarding a person's ability to perform everyday function. Each question is scored from 0-4. A score of 0 correlates to no function and complete inability to perform every day tasks to 80 correlating to normal function.
Measured: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Veterans Rand 12-item health survey (VR-12) score
The Veterans Rand 12-item health survey (VR-12) scores at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The VR-12 questionnaire is a series of 12 questions that evaluate a patient's physical and emotional health status. It is scored from 0 to 50, with 50 correlating to healthy mental and physical status.
Measured: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
TIme to physical therapy goals completion
Time to attainment of physical therapy (PT) goals (Ambulation 100 meters, independent transfer) measured during inpatient stay.
Measured: postoperative day 0-3
Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses
Day of surgery (pre-operative), POD 1 , and postoperative week 6 (±2 weeks) inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses)
Measured: Day of surgery (preoperative), postoperative day 1, postoperative week 6 (±2 weeks)
MRI Findings
MRI Findings (pre-operative, 1 yr, 2yr ). MRIs of the knee will be reviewed by the radiology department and their findings and changes noted and logged.
Measured: preoperative, 1 year, 2 years
Biomechanical findings
Biomechanical findings as assessed by EOS® imaging (pre-op, 6 weeks, 1 year)
Measured: preoperative, 6 weeks, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2019
- Study start24 Jul 2019
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital for Special Surgery, New York
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04082533
- Sponsor's protocol ID
- 2018-0660
- Status last verified
- Oct 2026
- First submitted
- 25 Jun 2019
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the primary outcome beginning 9 months and following 36 months after article publication. These data may be shared with investigators whose proposed use of data have been approved by an independent review committee for the purposes of a meta-analysis.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study
- ClinicalTrials.gov ID
- NCT04082533
- Acronym / sponsor ID
- 2018-0660
- Conditions
- Pain, Arthrofibrosis, Osteoarthritis, Knee
- Keywords
- total knee replacement, hydrocortisone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Hospital for Special Surgery, New YorkUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 9 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, total knee replacement patients will be determined to be stiff or non-stiff preoperatively. Stiffness designation is determined by preoperative range of motion (if flexion is < 100 degrees, or extension lag is > 10 degrees). The stiff and non-stiff groups will both be randomized to two groups to receive either intravenous hydrocortisone or a placebo at 3 intervals postoperatively. Patients will be followed up with in hospital and via the phone on postoperative day (POD) 1 and 2, as well as 6 weeks, 6 months, 1 year, and 2 years postoperatively. Patients will also have blood drawn preoperatively in the OR, on POD1, at their 6 week followup, and at their 1 and 2 year follow ups. This blood will be processed and analyzed.
Detailed description
TKA is the standard of care for treating patients suffering from end-stage knee arthritis and other disabling knee injuries. Indications have increased to ever younger patients and, combined with the aging US population, nearly 700,000 Americans receive TKAs each year. In spite of surgery, many patients experience persistent pain, stiffness or instability that negatively impacts their quality of life; up to 5% experience TKA failure in the first 10 years.
Presently, IV stress dose steroids is an accepted practice for bilateral knee replacement (BTKR) leading to decreased pain 24 hours after surgery and improved range of motion (ROM) on postoperative day 2 (POD2). These benefits are likely due to suppression of inflammation immediately after surgery. It is not clear if IV stress dose steroids improve ROM at later time points. Moreover, it is not clear if IV hydrocortisone improves clinical outcomes in unilateral TKA, where pain and joint stiffness remain significant challenges weeks after surgery. The investigators hypothesize that IV hydrocortisone will increase ROM at 6 weeks following surgery.
This study will enroll 132 patients that will be followed for up to 2 years. By integrating cell and molecular biology, biomechanics, and imaging technologies (including a CT scan at 1 year), this study is designed to comprehensively examine the long term effects of IV hydrocortisone on joint stiffness, pain, clinically relevant inflammatory states, and the synovium following unilateral TKA. Because subjects with variable ROMs will be enrolled in the study and followed over time, the findings may enable the development of biomarker prediction tools and the targeting of appropriate prevention and management measures for patients at highest risk of joint stiffness and subsequent surgical intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Stiffness Intravenous Hydrocortisone | Active comparator | Drug: HydrocortisoneTotal knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. |
| Stiffness Intravenous Placebo | Placebo comparator | Drug: Dextrose 5% in water (D5W)Total knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. |
| Non-stiff Intravenous Hydrocortisone | Active comparator | Drug: HydrocortisoneTotal knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. |
| Non-stiff Intravenous placebo | Placebo comparator | Drug: Dextrose 5% in water (D5W)Total knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision. |
Who may qualify
- Ages
- 18 to 83 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Elective primary unilateral total knee arthroplasty
- Osteoarthritis (OA) within the affected joint
- Patients of surgeons who have agreed to participate in the study
- Age ≥18 to 83 years
- American Society of Anesthesiologists (ASA) Physical Status 1-3
Key exclusion criteria (15 listed)
- Contraindication to regional anesthesia, non-steroidal anti-inflammatory drugs, or steroids
- Pre-operative oral steroid use in the past 3 months
- Body mass index (BMI) greater than or equal to 45
- Intraarticular steroid injections within two months of scheduled surgery in affected joint
- Non-English speaking
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisonePatients will be receiving 100 mg intravenous hydrocortisone every 8 hours, starting in the holding area roughly 2 hours prior to first incision. | Drug | Non-stiff Intravenous Hydrocortisone, Stiffness Intravenous Hydrocortisone |
| Dextrose 5% in water (D5W)Also: PlaceboPatients will be receiving a matched volume of D5W every 8 hours, starting in the holding area roughly 2 hours prior to first incision. | Drug | Non-stiff Intravenous placebo, Stiffness Intravenous Placebo |
Primary outcome
Postoperative Range of Motion (ROM)
Time frame: 6 weeks postoperative (±2 weeks)
The primary outcome is range of motion at patients' 6 week (±2 weeks) postoperative surgeon appointment.
11 secondary outcomes
Postoperative Stiffness
Time frame: 6 weeks postoperative (±2 weeks)
Numeric Rating Scale (NRS)
Time frame: baseline (preoperative), postoperative day (POD) 1, POD2, 6 weeks postop, 1 year postop, 2 years postop
PainDETECT Neuropathic Pain Score
Time frame: baseline (preoperative), 6 weeks postop, 1 year postop, 2 years postop
Opioid consumption
Time frame: pre-surgical screening (PSS and holding area), day of surgery (DOS), POD1, POD2 at 6 weeks, 6 months 1 year and 2 years postoperatively,
Knee injury and Osteoarthritis Outcome Score (KOOS Jr.)
Time frame: Preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Lower extremity Activity Survey (LEAS) scores
Time frame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Veterans Rand 12-item health survey (VR-12) score
Time frame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
TIme to physical therapy goals completion
Time frame: postoperative day 0-3
Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses
Time frame: Day of surgery (preoperative), postoperative day 1, postoperative week 6 (±2 weeks)
MRI Findings
Time frame: preoperative, 1 year, 2 years
Biomechanical findings
Time frame: preoperative, 6 weeks, 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the primary outcome beginning 9 months and following 36 months after article publication. These data may be shared with investigators whose proposed use of data have been approved by an independent review committee for the purposes of a meta-analysis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrocortisone and Dextrose 5% in water (D5W) in people with Pain and Arthrofibrosis, run by Hospital for Special Surgery, New York at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative Range of Motion (ROM) (time frame: 6 weeks postoperative (±2 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.