Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Vitamin D Status in Lower Extremity Joint Replacement Surgery Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2013 by Massachusetts General Hospital
Sponsor:
Collaborator:
BioTech Pharmacal
Information provided by (Responsible Party):
Sadeq A. Quraishi, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01858051
First received: May 16, 2013
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

In the United States, ~1 million elective hip or knee replacement surgeries are performed annually. With estimated surgical site infection (SSI) rates as high as 2.5%, this represents ~25,000 patients at risk of potentially avoidable morbidity following lower extremity joint replacement surgery. Although SSIs only account for 20% of all HAIs, they are a major risk factor for prosthetic joint infections (PJIs). Furthermore, UTIs have also been identified as an independent risk factor for infections of implanted hardware.

In general, the majority of PJIs become apparent within 3 months of hardware implantation, but deep infections may not be evident for up to one year after surgery. Hardware infections result in delayed healing, repeated surgical interventions, and long-term antibiotic therapy. PJIs are associated with an average increase in hospital LOS by 14 days, additional expenditures of up to $50,000 per infected joint, and a doubling of the mortality rate compared to uninfected lower extremity joint replacements.

Recent work from our group suggests that vitamin D insufficiency may be a risk factor for perioperative HAIs. The prevalence of vitamin D insufficiency is approximately 40% in elective joint replacement surgery patients, and perioperative 25(OH)D levels drop 30-40% in the setting of surgical stress, remaining 20% below baseline up to 3 months after surgery. To date, perioperative vitamin D optimization strategies have not been reported. Therefore, our goal is to study the effect of a single (pre-operative) versus a divided (pre-operative and on post-operative day 1) dose of cholecalciferol on perioperative vitamin D status in patients scheduled for elective hip or knee joint replacement surgery.


Condition Intervention Phase
Hypovitaminosis D
Dietary Supplement: Cholecalciferol
Dietary Supplement: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Bolus vs. Divided Cholecalciferol Dosing to Optimize Perioperative Vitamin D Status for Joint Replacement Surgery

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in vitamin D status 5 days following supplementation with cholecalciferol [ Time Frame: Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days ] [ Designated as safety issue: Yes ]
    Subjects will receive 150,000 IU or 100,000 IU cholecalciferol (vs. placebo) 3-7 days before surgery during their pre-operative assessment. Vitamin D status on the day of pre-operative assessment will be compared to vitamin D status on the day of surgery. To assess vitamin D status, we will measure serum: 1) 25-hydroxyvitamin D; 2) Parathyroid hormone; 3) Vitamin D binding protein; 4) LL-37; 5) Albumin; and 6) Calcium levels.


Secondary Outcome Measures:
  • Change in pre-surgical vitamin D status 1 day after surgery [ Time Frame: Patients will be followed between the day of surgery and an average duration of 1 day after surgery ] [ Designated as safety issue: No ]
    Subjects will receive either pre-operative supplementation with 150,000 IU or pre-operative supplementation with 100,000 IU cholecalciferol plus 50,000 IU cholecalciferol on post-operative day 1 (vs. placebo). Vitamin D status will be compared between the day of surgery and post-operative day 1. To assess vitamin D status, we will measure: 1) 25-hydroxyvitamin D; 2) Parathyroid hormone; 3) Vitamin D binding protein; 4) LL37; 5) Albumin; and 6) Calcium levels.

  • Change in pre-surgical vitamin D status 2 weeks after surgery [ Time Frame: Patients will be followed between the day of surgery and an average duration of 14 days after surgery ] [ Designated as safety issue: No ]
    Subjects will receive either pre-operative supplementation with 150,000 IU or pre-operative supplementation with 100,000 IU cholecalciferol plus 50,000 IU cholecalciferol on post-operative day 1 (vs. placebo). Vitamin D status will be compared between the day of surgery and post-operative day 10-18. To assess vitamin D status, we will measure: 1) 25-hydroxyvitamin D; 2) Parathyroid hormone; 3) Vitamin D binding protein; 4) LL37; 5) Albumin; and 6) Calcium levels.

  • Change in pre-surgical vitamin D status 3 months after surgery [ Time Frame: Patients will be followed between the day of surgery and an average of 90 days after surgery ] [ Designated as safety issue: No ]
    Subjects will receive either pre-operative supplementation with 150,000 IU or pre-operative supplementation with 100,000 IU cholecalciferol plus 50,000 IU cholecalciferol on post-operative day 1 (vs. placebo). Vitamin D status will be compared between the day of surgery and post-operative day 80-100. To assess vitamin D status, we will measure: 1) 25-hydroxyvitamin D; 2) Parathyroid hormone; 3) Vitamin D binding protein; 4) LL37; 5) Albumin; and 6) Calcium levels.


Other Outcome Measures:
  • Incidence of post-operative complications within 3 months of surgery [ Time Frame: Patients will be followed between the day of surgery and an average of 90 days after surgery ] [ Designated as safety issue: No ]
    Subjects will receive either pre-operative supplementation with 150,000 IU or pre-operative supplementation with 100,000 IU cholecalciferol plus 50,000 IU cholecalciferol on post-operative day 1 (vs. placebo). The incidence of post-operative complications will be assessed between the day of surgery and post-operative day 80-100. To assess the incidence of post-surgical complications, we will measure rates of: 1) pneumonia; 2) urinary tract infection; 3) surgical site infection; 5) sepsis/bacteremia; 6) infected hardware; 7) hospital readmission; and 8) mortality.


Estimated Enrollment: 175
Study Start Date: July 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cholecalciferol Bolus Dose
70 patients will receive a bolus pre-operative oral dose of 150,000 IU cholecalciferol 3-7 days before surgery
Dietary Supplement: Cholecalciferol
Active Comparator: Cholecalciferol Divided Dose
70 patients will receive an oral 100,000 IU cholecalciferol dose 3-7 days before surgery and an additional oral 50,000 IU cholecalciferol dose on post-operative day 1
Dietary Supplement: Cholecalciferol
Placebo Comparator: Sugar Pill
35 patients will receive a placebo pill orally 3-7 days before surgery
Dietary Supplement: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female
  • Age ≥18 years
  • English or Spanish speaking
  • Scheduled for preoperative clinic assessment
  • Scheduled to have elective hip or knee joint replacement surgery
  • Not taking more than 1000 IU of either cholecalciferol or ergocalciferol daily

Exclusion Criteria:

  • Unable to provide consent
  • Inability to comply with study protocol
  • History of anemia (hematocrit <25%)
  • History of renal stones or hypercalcemia
  • Conditions that can cause hypercalcemia (e.g. metastatic cancer, sarcoidosis, myeloma)
  • Medications that affect vitamin D metabolism (e.g. anti-epileptics, tuberculosis medication)
  • Already enrolled or planning to enroll in a research study that would conflict with full participation in the current study or confound the observation or interpretation of the study findings
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01858051

Contacts
Contact: Caitlin McCarthy, BA cmccarthy@psrtners.org
Contact: Livnat Blum, BA lblum@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
BioTech Pharmacal
Investigators
Principal Investigator: Sadeq A Quraishi, MD, MMSc Harvard Medical School, Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Sadeq A. Quraishi, Assistant Professor of Anaesthesia, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01858051     History of Changes
Other Study ID Numbers: 2013P001071
Study First Received: May 16, 2013
Last Updated: May 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Vitamin D
Perioperative immune regulation
LL-37
Hospital-acquired infection
Surgical site infections

Additional relevant MeSH terms:
Rickets
Avitaminosis
Vitamin D Deficiency
Bone Diseases
Bone Diseases, Metabolic
Calcium Metabolism Disorders
Deficiency Diseases
Malnutrition
Metabolic Diseases
Musculoskeletal Diseases
Nutrition Disorders
Cholecalciferol
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014