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

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ClinicalTrials.gov Identifier: NCT01272830
Recruitment Status : Completed
First Posted : January 10, 2011
Results First Posted : January 31, 2018
Last Update Posted : January 31, 2018
Sponsor:
Collaborators:
Summa Health System
Crystal Clinic Orthopaedic Center LLC
Information provided by (Responsible Party):
IC-MedTech Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Edematous
Synovitis
Foreign Body Reaction
Osteolysis
Interventions Drug: Placebo
Drug: Apatone®B
Enrollment 57
Recruitment Details A total of 57 subjects were consented to participate.
Pre-assignment Details

Following consenting, 6 subjects did not meet the study inclusion/exclusion criteria, thus never received the study drug.

1 - Abnormal Liver Panel: very low Hemoglobin/Hematocrit levels

1 - Glucose-6-phosphate dehydrogenase (G6PD) deficiency

3 - X-rays revealed loose or mal-positioned component(s)

1 - Prescribed steroids prior to study drug

Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Period Title: Overall Study
Started 25 26
Completed 17 21
Not Completed 8 5
Arm/Group Title Oral Apatone®B Placebo Total
Hide Arm/Group Description

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Total of all reporting groups
Overall Number of Baseline Participants 17 21 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 21 participants 38 participants
62.1  (9.5) 65.4  (9.6) 63.9  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 21 participants 38 participants
Female
9
  52.9%
12
  57.1%
21
  55.3%
Male
8
  47.1%
9
  42.9%
17
  44.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 17 participants 21 participants 38 participants
17
 100.0%
21
 100.0%
38
 100.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 17 participants 21 participants 38 participants
96.7  (20.4) 100  (16.8) 99  (18.5)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 17 participants 21 participants 38 participants
171.7  (9.9) 169.8  (8.6) 170.6  (9.2)
Time elapsed since TKA   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 21 participants 38 participants
2.5  (1.9) 4.0  (3.3) 3.3  (2.9)
[1]
Measure Description: TKA - Total Knee Arthroplasty
Initial Pain Visual Analog Scale (VAS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 17 participants 21 participants 38 participants
57  (24.1) 46.8  (24.9) 51.4  (25.1)
[1]
Measure Description:

VAS Scale range (0-100 )

Higher VAS score indicate worst knee pain.

1.Primary Outcome
Title Pain Visual Analog Scale (VAS)
Hide Description

Pain Visual Analog Scale (VAS)

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

Time Frame 13-weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description:

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 57  (24.1) 46.8  (24.9)
13 Weeks 39.7  (27.4) 39.1  (29.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Change from baseline data.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments Significance threshold p<0.05
Method paired t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Changes from baseline data
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments Significant threshold p<0.05
Method paired t-test
Comments [Not Specified]
2.Secondary Outcome
Title Surrogate Endpoint Markers (SEBs)
Hide Description

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
Time Frame 13 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description:

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
HSS Pain Walking- Baseline 5.9  (5.4) 6.9  (4.3)
HSS Pain Walking-13 Weeks 9.1  (6.2) 7.9  (4.4)
HSS Total-Baseline 69.6  (14.3) 71.9  (11.6)
HSS Total-13 Weeks 76.6  (16.7) 74.5  (11.1)
KSS Total Pain-Baseline 56.2  (19.4) 59.0  (14.0)
KSS Total Pain-13 Week 65.3  (20.1) 63.0  (18.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Change from baseline data (HSS pain walking)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0226
Comments Significance threshold p<0.5
Method paired
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Change from baseline data (HSS total score)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0375
Comments Significance threshold P<0.05
Method paired t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Change from baseline data (KSS knee pain)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0391
Comments Significance threshold p<0.05
Method paired t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Changes from baseline data (HSS pain walking)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2137
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from baseline data (HSS total score)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1312
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from baseline data (KSS knee pain)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1578
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
3.Secondary Outcome
Title TGFBeta Levels
Hide Description

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.

Time Frame Baseline and 13 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description:

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline 3197.4  (2793.5) 2089.2  (2879.7)
13 Weeks 2572.2  (2879.7) 1572.2  (1803.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Changes from baseline data
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments Significance threshold p<0.05
Method t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from baseline data
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments Significant threshold p<0.05
Method paired t-test
Comments [Not Specified]
4.Secondary Outcome
Title Deoxypyridinoline Levels
Hide Description

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

Time Frame Baseline and 13 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description:

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: nmol/L
Basline 8.0  (6.0) 5.9  (1.3)
13 Weeks 6.4  (1.5) 6.1  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Apatone®B
Comments Change from baseline data
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments Significance threshold p<0.05
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Changes from baseline data
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method paired t-test
Comments Significant threshold p<0.05
Time Frame [Not Specified]
Adverse Event Reporting Description All adverse events (AEs) were classified by the investigator with respect to severity (mild, moderate, severe and potentially life threatening). No AEs classified as potentially life threatening were reported during the course of this study, nor were there any deaths.
 
Arm/Group Title Oral Apatone®B Placebo
Hide Arm/Group Description

An amalgam of Vitamins C & K3

Apatone®B: Two capsules taken twice daily with meals

Oral capsule of similar appearance and taste without Apatone®B

Placebo: Two capsules taken twice daily with meals

All-Cause Mortality
Oral Apatone®B Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)      0/21 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Oral Apatone®B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/17 (5.88%)      0/21 (0.00%)    
Musculoskeletal and connective tissue disorders     
Knee pain – hospitalization * [1]  1/17 (5.88%)  1 0/21 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Outcome - not recovered, ongoing. Did not finish study; revision knee surgery elected before trial completion.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Apatone®B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/17 (82.35%)      7/21 (33.33%)    
Blood and lymphatic system disorders     
13th week elevated PT, PTT *  0/17 (0.00%)  0 1/21 (4.76%)  1
Repeated PT, PTT one week later *  0/17 (0.00%)  0 1/21 (4.76%)  1
Injury, poisoning and procedural complications     
Fall outdoors, hit head *  1/17 (5.88%)  1 0/21 (0.00%)  0
Pulled muscle right knee *  1/17 (5.88%)  1 0/21 (0.00%)  0
Slipped on ice; cracked rib *  1/17 (5.88%)  1 0/21 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Knee pain *  1/17 (5.88%)  1 1/21 (4.76%)  1
Knee discomfort left and right *  2/17 (11.76%)  2 1/21 (4.76%)  1
Entire body ached *  1/17 (5.88%)  1 0/21 (0.00%)  0
Extreme knee pain *  1/17 (5.88%)  1 0/21 (0.00%)  0
Muscle aches *  1/17 (5.88%)  1 0/21 (0.00%)  0
Painful knee aspiration *  1/17 (5.88%)  1 0/21 (0.00%)  0
Right knee pain *  1/17 (5.88%)  1 0/21 (0.00%)  0
Swelling of knees *  1/17 (5.88%)  1 0/21 (0.00%)  0
Knee discomfort right *  0/17 (0.00%)  0 1/21 (4.76%)  1
Knee pain left *  0/17 (0.00%)  0 2/21 (9.52%)  2
Respiratory, thoracic and mediastinal disorders     
Asthma attack *  1/17 (5.88%)  1 0/21 (0.00%)  0
Vascular disorders     
Right calf pain, possible blood clot *  1/17 (5.88%)  1 0/21 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
limited accrual due to meeting stringent study inclusion/exclusion criteria.Stringent inclusion/exclusion created to allow SEB analyses w/o interference or artifacts,& not due to study drug issues,interaction or limitations.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Published articles to be reviewed/approved by IC-MedTech prior to publication.
Results Point of Contact
Name/Title: Thomas Bear, MD
Organization: Clinic Orthopaedic Center
Phone: 330-375-3906
Responsible Party: IC-MedTech Corporation
ClinicalTrials.gov Identifier: NCT01272830     History of Changes
Other Study ID Numbers: Summa-09136
First Submitted: December 17, 2010
First Posted: January 10, 2011
Results First Submitted: July 19, 2017
Results First Posted: January 31, 2018
Last Update Posted: January 31, 2018