Trial Outcomes & Findings for Double-Blinded Clinical Trial Using Apatone®B for Symptomatic Postoperative Total Joint Replacements (NCT NCT01272830)

NCT ID: NCT01272830

Last Updated: 2018-01-31

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

13-weeks

Results posted on

2018-01-31

Participant Flow

A total of 57 subjects were consented to participate.

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

Participant milestones

Participant milestones
Measure	Oral Apatone®B An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Overall Study STARTED	25	26
Overall Study COMPLETED	17	21
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral Apatone®B n=17 Participants An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 Participants Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals	Total n=38 Participants Total of all reporting groups
Age, Continuous	62.1 years STANDARD_DEVIATION 9.5 • n=99 Participants	65.4 years STANDARD_DEVIATION 9.6 • n=107 Participants	63.9 years STANDARD_DEVIATION 9.7 • n=206 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	12 Participants n=107 Participants	21 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	9 Participants n=107 Participants	17 Participants n=206 Participants
Region of Enrollment United States	17 Participants n=99 Participants	21 Participants n=107 Participants	38 Participants n=206 Participants
Weight	96.7 kilograms STANDARD_DEVIATION 20.4 • n=99 Participants	100 kilograms STANDARD_DEVIATION 16.8 • n=107 Participants	99 kilograms STANDARD_DEVIATION 18.5 • n=206 Participants
Height	171.7 centimeters STANDARD_DEVIATION 9.9 • n=99 Participants	169.8 centimeters STANDARD_DEVIATION 8.6 • n=107 Participants	170.6 centimeters STANDARD_DEVIATION 9.2 • n=206 Participants
Time elapsed since TKA	2.5 years STANDARD_DEVIATION 1.9 • n=99 Participants	4.0 years STANDARD_DEVIATION 3.3 • n=107 Participants	3.3 years STANDARD_DEVIATION 2.9 • n=206 Participants
Initial Pain Visual Analog Scale (VAS)	57 units on a scale STANDARD_DEVIATION 24.1 • n=99 Participants	46.8 units on a scale STANDARD_DEVIATION 24.9 • n=107 Participants	51.4 units on a scale STANDARD_DEVIATION 25.1 • n=206 Participants

PRIMARY outcome

Timeframe: 13-weeks

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

Outcome measures

Outcome measures
Measure	Oral Apatone®B n=17 Participants An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 Participants Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Pain Visual Analog Scale (VAS) Baseline	57 units on a scale Standard Deviation 24.1	46.8 units on a scale Standard Deviation 24.9
Pain Visual Analog Scale (VAS) 13 Weeks	39.7 units on a scale Standard Deviation 27.4	39.1 units on a scale Standard Deviation 29.1

SECONDARY outcome

Timeframe: 13 weeks

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

Outcome measures

Outcome measures
Measure	Oral Apatone®B n=17 Participants An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 Participants Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Surrogate Endpoint Markers (SEBs) HSS Pain Walking- Baseline	5.9 units on a scale Standard Deviation 5.4	6.9 units on a scale Standard Deviation 4.3
Surrogate Endpoint Markers (SEBs) HSS Total-Baseline	69.6 units on a scale Standard Deviation 14.3	71.9 units on a scale Standard Deviation 11.6
Surrogate Endpoint Markers (SEBs) HSS Total-13 Weeks	76.6 units on a scale Standard Deviation 16.7	74.5 units on a scale Standard Deviation 11.1
Surrogate Endpoint Markers (SEBs) KSS Total Pain-Baseline	56.2 units on a scale Standard Deviation 19.4	59.0 units on a scale Standard Deviation 14.0
Surrogate Endpoint Markers (SEBs) HSS Pain Walking-13 Weeks	9.1 units on a scale Standard Deviation 6.2	7.9 units on a scale Standard Deviation 4.4
Surrogate Endpoint Markers (SEBs) KSS Total Pain-13 Week	65.3 units on a scale Standard Deviation 20.1	63.0 units on a scale Standard Deviation 18.4

SECONDARY outcome

Timeframe: Baseline and 13 Weeks

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.

Outcome measures

Outcome measures
Measure	Oral Apatone®B n=17 Participants An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 Participants Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
TGFBeta Levels Baseline	3197.4 pg/mL Standard Deviation 2793.5	2089.2 pg/mL Standard Deviation 2879.7
TGFBeta Levels 13 Weeks	2572.2 pg/mL Standard Deviation 2879.7	1572.2 pg/mL Standard Deviation 1803.9

SECONDARY outcome

Timeframe: Baseline and 13 Weeks

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

Outcome measures

Outcome measures
Measure	Oral Apatone®B n=17 Participants An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 Participants Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Deoxypyridinoline Levels 13 Weeks	6.4 nmol/L Standard Deviation 1.5	6.1 nmol/L Standard Deviation 1.8
Deoxypyridinoline Levels Basline	8.0 nmol/L Standard Deviation 6.0	5.9 nmol/L Standard Deviation 1.3

Adverse Events

Oral Apatone®B

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oral Apatone®B n=17 participants at risk An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 participants at risk Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Musculoskeletal and connective tissue disorders Knee pain - hospitalization	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.

Other adverse events

Additional Information

Thomas Bear, MD

Clinic Orthopaedic Center

Phone: 330-375-3906

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Published articles to be reviewed/approved by IC-MedTech prior to publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Oral Apatone®B n=17 participants at risk An amalgam of Vitamins C \& K3 Apatone®B: Two capsules taken twice daily with meals	Placebo n=21 participants at risk Oral capsule of similar appearance and taste without Apatone®B Placebo: Two capsules taken twice daily with meals
Musculoskeletal and connective tissue disorders Knee pain	5.9% 1/17 • Number of events 1 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.	4.8% 1/21 • Number of events 1 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.
Musculoskeletal and connective tissue disorders Knee discomfort left and right	11.8% 2/17 • Number of events 2 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.	4.8% 1/21 • Number of events 1 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.
Respiratory, thoracic and mediastinal disorders Asthma attack	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Entire body ached	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Extreme knee pain	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Injury, poisoning and procedural complications Fall outdoors, hit head	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Muscle aches	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Painful knee aspiration	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Injury, poisoning and procedural complications Pulled muscle right knee	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Vascular disorders Right calf pain, possible blood clot	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Right knee pain	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Injury, poisoning and procedural complications Slipped on ice; cracked rib	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Musculoskeletal and connective tissue disorders Swelling of knees	5.9% 1/17 • Number of events 1 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.	0.00% 0/21 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.
Blood and lymphatic system disorders 13th week elevated PT, PTT	0.00% 0/17 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.	4.8% 1/21 • Number of events 1 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.
Musculoskeletal and connective tissue disorders Knee discomfort right	0.00% 0/17 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.	4.8% 1/21 • Number of events 1 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.
Musculoskeletal and connective tissue disorders Knee pain left	0.00% 0/17 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.	9.5% 2/21 • Number of events 2 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.
Blood and lymphatic system disorders Repeated PT, PTT one week later	0.00% 0/17 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.	4.8% 1/21 • Number of events 1 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.