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Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications

Primary Purpose

Hip Arthropathy, Knee Arthropathy, Vitamin D Deficiency

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hip Arthropathy focused on measuring joint replacement, hip arthroplasty, knee arthroplasty, clinical outcomes, Vitamin D Deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective unilateral primary TJA for osteoarthritis
  • Patients with a pre-operative serum 25(OH)D levels ≥10 ng/mL
  • Patients who consent to the study

Exclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective primary TJA with a pre-operative serum 25(OH)D2,3 level <10 ng/mL
  • Patients undergoing revision surgery
  • Patients lacking mental capacity to comply with study procedures
  • Patients with serum 25(OH)D levels between 10-29 ng/dL refusing to stop their current Vitamin D and multivitamins supplementations
  • Hypercalcemia (total calcium >10.6 mg/dL or ionized serum calcium >5.4mg/dL)
  • History of nephrolithiasis
  • Granulomatous disease
  • Dialysis and advanced kidney disease
  • Previous infection/septic arthritis
  • Inability to swallow Vitamin D3 pills
  • Allergy to Vitamin D3 (It is estimated that 1 in 300 individuals may have an allergy with skin manifestations 17)
  • Hypocalcemia (<8.5 mg/dL)
  • Chronic kidney disease (eGFR <60 mL/minute)
  • Known hyperparathyroidism
  • Known osteoporosis/insufficiency stress fractures (if normal stresses are applied to an abnormal bone)
  • Pregnancy

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

No Intervention

Arm Label

Low Vitamin D3 Supplementation

High Vitamin D3 Supplementation

No supplementation

Arm Description

Subjects enrolled into Group 1 (low-dose Vitamin D3 supplementation) will receive 800 IU of oral Vitamin D3 (Cholecalciferol) daily for 4 weeks prior to surgery, followed by 800 IU of oral Vitamin D3 daily for 3 months after surgery. Vitamin D3 supplementation will be given for a total of 4 months. Supplementing Vitamin D-deficient patients with a minimum of 800 IU of Vitamin D3 daily is supported by the IOM.

Subjects enrolled into Group 2 (high-dose Vitamin D3 supplementation) will receive 50,000 IU of oral Vitamin D3 (Cholecalciferol) twice per week for 1 weeks followed by 50,000 IU once per week for 3 weeks prior to surgery. After surgery they will receive 50,000 IU of oral Vitamin D3 once per week for 4 weeks followed by 800 IU daily for 8 weeks. Vitamin D3 supplementation will be given for a total of 4 months.

Subjects with serum 25(OH)D level ≥30ng/mL will not receive any Vitamin D supplementation both pre- and postoperatively, as these are considered sufficient. These control patients will be asked to take any supplements containing Vitamin D for the duration of their participation in the trial. All patients in group 3 will have their serum 25(OH)D checked at 3 months after the surgery.

Outcomes

Primary Outcome Measures

Readmission, reoperation, wound complications, and PJI
adverse events

Secondary Outcome Measures

Vitamin D status
Vitamin D levels will be drawn initially, during supplementation and following
Patient-Reported Outcomes Measurement Information System (PROMIS)
set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children.41 to 78.3 with higher scores representing worse pain impact.
Pain Levels: visual analog scale (VAS)
Scores on the VAS pain scale range from 0-10 with 0 being no pain and 10 being the highest pain level imaginable.
Hip disability and Osteoarthritis Outcome Score (HOOS)
Scores range from 0 to 100 with a score of 0 indicating the worst possible hip symptoms and 100 indicating no hip symptoms

Full Information

First Posted
January 9, 2020
Last Updated
August 14, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital, Newton-Wellesley Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04229368
Brief Title
Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications
Official Title
Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital, Newton-Wellesley Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Vitamin D status has been shown to have an effect on post-operative outcomes in total joint arthroplasty. The goal of this study is to determine if pre-operative supplementation and correction of Vitamin D deficiency can reduce postoperative complications.
Detailed Description
Total joint arthroplasty (TJA) is one of the most common surgical procedures performed in the United States (US), with approximately 2.5 million individuals with total hip arthroplasties (THAs) and 4.7 million individuals with total knee arthroplasties (TKAs) in 2010. Patients who undergo TJA commonly have Vitamin D deficiency, with rates reported to be 24-61% in primary TJA patients. Vitamin D deficiency affects women and minorities at high rates, in addition to non-Hispanic whites. Previous studies demonstrated that Vitamin D deficiency poorly impacts outcomes after various surgical procedures. Specifically in TJA patients, recent studies show a higher rate of Vitamin D deficiency in periprosthetic joint infection (PJI) patients, and a higher rate of postoperative complications and infection in revision TJA patients with low Vitamin D. In a PJI mouse model, Vitamin D-deficient mice were shown to have an increased bacterial burden when compared to Vitamin D-deficient mice that received "rescue" cholecalciferol (Vitamin D3) supplementation. Bacterial burden was similarly decreased between normal mice and the Vitamin D-deficient "rescue" mice receiving supplementation. A single dose of Vitamin D3 supplementation in Vitamin D-deficient mice using the same mouse model reversed the effect of PJI by decreasing bacterial burden and neutrophil infiltration. The serum concentration of 25-hydroxycholecalciferol or 25-hydroxyvitamin D (25(OH)D) is the most accurate measure of stores of Vitamin D in the body. There are currently different recommendations regarding the optimal serum 25(OH)D level for bone health, the optimal daily intake of Vitamin D, and the treatments for Vitamin D deficiency or insufficiency. These controversial topics do not provide clear clinical guidance on how to optimize Vitamin D levels in surgical patients to reduce complication rates. The US Institute of Medicine (IOM) committee recommended a 25(OH)D level >20 ng/mL but other organizations recommend ≥30 ng/mL. At present, deficient levels of Vitamin D are generally defined as a 25(OH)D <20 ng/ml, relative insufficiency as 20 to 29 ng/mL, and sufficient levels as ≥ 30 ng/ml. In 2011, the IOM established Recommended Dietary Allowances (RDAs) for Vitamin D of 600-800 IU/d in order to achieve a 25(OH)D level of 20 ng/ml for 97.5% of the general population. The debate concerns recommendations based upon population science, in contrast to care of an individual patient. Thus, there is continuing debate among several groups that recommend higher Vitamin D3 doses and 25(OH)D levels of ≥30 ng/mL for optimal bone health and in high-risk individuals with osteoporosis. The National Osteoporosis Foundation recommends 800 to 1000 IU Vitamin D3 daily for adults aged 50 years and older, as do the International Osteoporosis Foundation and Endocrine Society. The Endocrine Society recommended even higher doses up to 1500 to 2000 IU/d of Vitamin D3 for older adults. For Vitamin D deficiency, the recommended treatment is 50,000 units of Vitamin D3 weekly for 8 weeks with an assay repeat to determine whether Vitamin D-sufficiency ≥30ng/mL was achieved. The proposed study was designed in light of debated recommendations in the literature and should result in rigorous new information about 25(OH)D levels achieved with different doses of Vitamin D3 supplementation and their impact on post-TJA complications. There are no current studies in literature examining whether preoperative supplementation and correction of Vitamin D deficiency may reduce complications following TJA. The aim of this randomized controlled trial is to evaluate the ability of different doses (low and high dose) of Vitamin D3 supplementation to affect adverse events and functional outcomes following total joint arthroplasty surgery. To conduct this study, investigators propose randomizing subjects with 25(OH)D levels between 10 and 29 ng/mL to receive different doses of Vitamin D to assess the effects of Vitamin D3 supplementation dosage on postoperative TJA complication rates. Consented patients with serum 25(OH)D levels equal or greater than 30 ng/dL will be included in the control group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hip Arthropathy, Knee Arthropathy, Vitamin D Deficiency
Keywords
joint replacement, hip arthroplasty, knee arthroplasty, clinical outcomes, Vitamin D Deficiency

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
900 patients to be enrolled total including controls, and two additional study arms
Allocation
Randomized
Enrollment
900 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Vitamin D3 Supplementation
Arm Type
Active Comparator
Arm Description
Subjects enrolled into Group 1 (low-dose Vitamin D3 supplementation) will receive 800 IU of oral Vitamin D3 (Cholecalciferol) daily for 4 weeks prior to surgery, followed by 800 IU of oral Vitamin D3 daily for 3 months after surgery. Vitamin D3 supplementation will be given for a total of 4 months. Supplementing Vitamin D-deficient patients with a minimum of 800 IU of Vitamin D3 daily is supported by the IOM.
Arm Title
High Vitamin D3 Supplementation
Arm Type
Active Comparator
Arm Description
Subjects enrolled into Group 2 (high-dose Vitamin D3 supplementation) will receive 50,000 IU of oral Vitamin D3 (Cholecalciferol) twice per week for 1 weeks followed by 50,000 IU once per week for 3 weeks prior to surgery. After surgery they will receive 50,000 IU of oral Vitamin D3 once per week for 4 weeks followed by 800 IU daily for 8 weeks. Vitamin D3 supplementation will be given for a total of 4 months.
Arm Title
No supplementation
Arm Type
No Intervention
Arm Description
Subjects with serum 25(OH)D level ≥30ng/mL will not receive any Vitamin D supplementation both pre- and postoperatively, as these are considered sufficient. These control patients will be asked to take any supplements containing Vitamin D for the duration of their participation in the trial. All patients in group 3 will have their serum 25(OH)D checked at 3 months after the surgery.
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
cholecalciferol
Intervention Description
Vitamin D will be given at doses commonly given to patients with low vitamin D levels
Primary Outcome Measure Information:
Title
Readmission, reoperation, wound complications, and PJI
Description
adverse events
Time Frame
Preoperative visit to three months post-op
Secondary Outcome Measure Information:
Title
Vitamin D status
Description
Vitamin D levels will be drawn initially, during supplementation and following
Time Frame
Day of surgery to to three months post-op
Title
Patient-Reported Outcomes Measurement Information System (PROMIS)
Description
set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children.41 to 78.3 with higher scores representing worse pain impact.
Time Frame
Preoperative visit to three months post-op
Title
Pain Levels: visual analog scale (VAS)
Description
Scores on the VAS pain scale range from 0-10 with 0 being no pain and 10 being the highest pain level imaginable.
Time Frame
Preoperative visit to three months post-op
Title
Hip disability and Osteoarthritis Outcome Score (HOOS)
Description
Scores range from 0 to 100 with a score of 0 indicating the worst possible hip symptoms and 100 indicating no hip symptoms
Time Frame
Preoperative visit to three months post-op

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients ≥18 years of age undergoing elective unilateral primary TJA for osteoarthritis Patients with a pre-operative serum 25(OH)D levels ≥10 ng/mL Patients who consent to the study Exclusion Criteria: Adult patients ≥18 years of age undergoing elective primary TJA with a pre-operative serum 25(OH)D2,3 level <10 ng/mL Patients undergoing revision surgery Patients lacking mental capacity to comply with study procedures Patients with serum 25(OH)D levels between 10-29 ng/dL refusing to stop their current Vitamin D and multivitamins supplementations Hypercalcemia (total calcium >10.6 mg/dL or ionized serum calcium >5.4mg/dL) History of nephrolithiasis Granulomatous disease Dialysis and advanced kidney disease Previous infection/septic arthritis Inability to swallow Vitamin D3 pills Allergy to Vitamin D3 (It is estimated that 1 in 300 individuals may have an allergy with skin manifestations 17) Hypocalcemia (<8.5 mg/dL) Chronic kidney disease (eGFR <60 mL/minute) Known hyperparathyroidism Known osteoporosis/insufficiency stress fractures (if normal stresses are applied to an abnormal bone) Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonia F Chen, MD
Phone
617-525-5935
Email
afchen@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonia F Chen, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonia F Chen, MD, MBA
Phone
617-525-5935
Email
afchen@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Antonia F Chen, MD, MBA

12. IPD Sharing Statement

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Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications

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