Title

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

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    menadiol ...
  • Study Participants

    57
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.
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 Started
Oct 31
2010
Primary Completion
Dec 31
2014
Study Completion
Dec 31
2015
Results Posted
Jan 31
2018
Last Update
Jan 31
2018

Drug Placebo

Two capsules taken twice daily with meals

Drug Apatone®B

Two capsules taken twice daily with meals

oral Apatone®B Experimental

An amalgam of Vitamins C & K3

Placebo Placebo Comparator

Oral capsule of similar appearance and taste without Apatone®B

Criteria

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

Summary

Oral Apatone®B

Placebo

All Events

Event Type Organ System Event Term Oral Apatone®B Placebo

Pain Visual Analog Scale (VAS)

Pain Visual Analog Scale (VAS) Scale range (0-100) A higher VAS score indicate worse knee pain

Oral Apatone®B

13 Weeks

39.7
units on a scale (Mean)
Standard Deviation: 27.4

Baseline

57.0
units on a scale (Mean)
Standard Deviation: 24.1

Placebo

13 Weeks

39.1
units on a scale (Mean)
Standard Deviation: 29.1

Baseline

46.8
units on a scale (Mean)
Standard Deviation: 24.9

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.

Oral Apatone®B

13 Weeks

2572.2
pg/mL (Mean)
Standard Deviation: 2879.7

Baseline

3197.4
pg/mL (Mean)
Standard Deviation: 2793.5

Placebo

13 Weeks

1572.2
pg/mL (Mean)
Standard Deviation: 1803.9

Baseline

2089.2
pg/mL (Mean)
Standard Deviation: 2879.7

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

Oral Apatone®B

HSS Pain Walking-13 Weeks

9.1
units on a scale (Mean)
Standard Deviation: 6.2

HSS Pain Walking- Baseline

5.9
units on a scale (Mean)
Standard Deviation: 5.4

HSS Total-13 Weeks

76.6
units on a scale (Mean)
Standard Deviation: 16.7

HSS Total-Baseline

69.6
units on a scale (Mean)
Standard Deviation: 14.3

KSS Total Pain-13 Week

65.3
units on a scale (Mean)
Standard Deviation: 20.1

KSS Total Pain-Baseline

56.2
units on a scale (Mean)
Standard Deviation: 19.4

Placebo

HSS Pain Walking-13 Weeks

7.9
units on a scale (Mean)
Standard Deviation: 4.4

HSS Pain Walking- Baseline

6.9
units on a scale (Mean)
Standard Deviation: 4.3

HSS Total-13 Weeks

74.5
units on a scale (Mean)
Standard Deviation: 11.1

HSS Total-Baseline

71.9
units on a scale (Mean)
Standard Deviation: 11.6

KSS Total Pain-13 Week

63.0
units on a scale (Mean)
Standard Deviation: 18.4

KSS Total Pain-Baseline

59.0
units on a scale (Mean)
Standard Deviation: 14.0

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

Oral Apatone®B

13 Weeks

6.4
nmol/L (Mean)
Standard Deviation: 1.5

Basline

8.0
nmol/L (Mean)
Standard Deviation: 6.0

Placebo

13 Weeks

6.1
nmol/L (Mean)
Standard Deviation: 1.8

Basline

5.9
nmol/L (Mean)
Standard Deviation: 1.3

Total

38
Participants

Age, Continuous

63.9
years (Mean)
Standard Deviation: 9.7

Height

170.6
centimeters (Mean)
Standard Deviation: 9.2

Initial Pain Visual Analog Scale (VAS)

51.4
units on a scale (Mean)
Standard Deviation: 25.1

Time elapsed since TKA

3.3
years (Mean)
Standard Deviation: 2.9

Weight

99
kilograms (Mean)
Standard Deviation: 18.5

Region of Enrollment

Sex: Female, Male

Overall Study

Oral Apatone®B

Placebo