Double-Blinded Clinical Trial Using Apatone®B for Symptomatic Postoperative Total Joint Replacements (Apatone-B)

A Prospective Double-Blinded Clinical Trial Using Apatone®B for Care and Treatment of Proven Non-Infected Symptomatic Postoperative Total Joint Arthroplasties

This research study is being conducted to determine if taking oral (by mouth in pill form) Apatone®B (a combination of Vitamins C and K3) will reduce chronic joint discomfort and improve function of non-infected symptomatic postoperative total joint replacements.

Study Overview

• Status: Completed
• Conditions: Synovitis; Osteolysis; Edematous; Foreign Body Reaction
• Intervention / Treatment: Drug: Apatone®B; Drug: Placebo

Detailed Description

To perform a prospective, randomized, double-blind clinical trial to determine if oral Apatone®B, an amalgam of vitamins C and K3, has a therapeutic efficacy beyond the conservative care customarily used to reduce inflammatory synovitis and to increase the functional capacity of proven non-infected symptomatic postoperative total joint replacements.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Akron, Ohio, United States, 44310
      • Summa Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Postoperative Total joint replacement with osteoarthritis as the underlying pathology
• Proven non-infected symptomatic Total Joint Arthroplasty (TJA) (joint implanted for >12 months post-op)
• Age (50 to 85 years of age); based on a 10% trim of the age distribution for Summa Health System TJAs (7/1/08-6/30/2009).

Exclusion Criteria:

• An infection of any kind (prior to, or during the study)
• Rheumatoid arthritis as the underlying pathology
• Cortisone injection received <6 months prior to study enrollment
• Insulin dependent diabetes
• Diagnosed immunodeficiency
• On dialysis or have poor kidney function
• Anti-coagulant medication (e.g., Coumadin or >100mg of Aspirin daily)
• Anti-seizure medication (e.g., Dilantin)
• Steroidal medication (e.g., Prednisone, Advair or Symbicort)
• NSAIDS (e.g., Celebrex or Toradol); a 14-day washout period will be allowed
• bisphosphonates (e.g., Fosamax, Actonel, Aredia, Didronel, Boniva or Reclast)
• hormonal therapy (e.g., Estrogen, Progesterone or Testosterone)
• Cancer (active or in remission)
• Planned concurrent vitamins exceeding a standard daily multivitamin or exceeding the Recommended Daily Allowance (RDA) for individual vitamins if used alone; a 72 hour wash out period will be allowed
• A glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Pregnant or lactating; females who are in their reproductive years must have a negative serum pregnancy
• Lactose intolerant
• Citric acid intolerant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: oral Apatone®B; An amalgam of Vitamins C & K3	Drug: Apatone®B; Two capsules taken twice daily with meals
PLACEBO_COMPARATOR: Placebo; Oral capsule of similar appearance and taste without Apatone®B	Drug: Placebo; Two capsules taken twice daily with meals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Visual Analog Scale (VAS)	Pain Visual Analog Scale (VAS) Scale range (0-100) A higher VAS score indicate worse knee pain	13-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surrogate Endpoint Markers (SEBs)	HSS = Hospital for Special Surgery Knee Score , KSS = Knee Society Knee Score.; Scale range HSS total: 100-90 Excellent; 80-89 Very Good; 70-79 Good; 60-69 Fair; below 60 Poor; Scale range HSS pain walking: No Pain 15; Mild Pain 10; Moderate Pain 5; Severe Pain 0 (**this is an element of the HSS total); Scale range KSS: 80-100 Excellent; 70-79 Good; 60-69 Fair; below 60 Poor	13 weeks
TGFBeta Levels	The final synovial aspirates obtained from the symptomatic knee of each subject were analyzed using Quantikine and Pyrilinks-D enzyme-linked immunosorbent assay kits from R&D Systems (Minneapolis, MN) and Metra Biosystems (Mountain View, CA), respectively. Lower TGFBeta concentrations represent a better outcome.	Baseline and 13 Weeks
Deoxypyridinoline Levels	The final synovial aspirates obtained from the symptomatic knee of each subject were analyzed using Quantikine and Pyrlinks-D enzyme-linked immunosorbent assay kits from R&D Systems(minneapolis, MN) and Metra Biosystems (Mountain View, CA) respectively. Lower DPD concentrations represent a better outcome	Baseline and 13 Weeks

Collaborators and Investigators

• Sponsor: IC-MedTech Corporation
• Collaborators: Summa Health System; Crystal Clinic Orthopaedic Center LLC
• Investigators: Principal Investigator: Thomas F Bear, MD, Crystal Clinic Orthopaedic Center LLC; Study Director: Mark W Kovacik, BS, Summa Health System

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: December 17, 2010
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (ESTIMATE): January 10, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: total joint arthroplasty; synovitis; osteolysis; ALVAL (Aseptic Lymphocyte-Dominant Vasculitis-Associated Lesion); periprosthetic metallosis
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Wounds and Injuries; Joint Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Resorption; Synovitis; Foreign Bodies; Foreign-Body Reaction; Osteolysis
• Other Study ID Numbers: Summa-09136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO