Trial Outcomes & Findings for Follow-Up Study Evaluating The Long Term Safety and Efficacy of BST-CarGel and Microfracture Repair of the Knee (NCT NCT01246895)

NCT ID: NCT01246895

Last Updated: 2018-01-24

Results Overview

Degree of lesion filling (repair tissue volume) as measured by quantitative MRI at 5 Years post-treatment compared to the debrided lesion 1-month post-treatment (baseline).

• Recruitment status: COMPLETED
• Target enrollment: 67 participants
• Primary outcome timeframe: 5 years
• Results posted on: 2018-01-24

Participant Flow

All eligible subjects who were treated under Protocol CG-CIP01-P and completed the required 12-month follow-up period were asked to participate in this follow-up study. Ultimately, 67 subjects signed an ICF to enter the study and the screening process.

Participant milestones

Measure	Microfracture + BST-CarGel Microfracture with BST-CarGel	Microfracture Alone Microfracture without BST-CarGel
Overall Study STARTED	37	30
Overall Study COMPLETED	34	26
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Follow-Up Study Evaluating The Long Term Safety and Efficacy of BST-CarGel and Microfracture Repair of the Knee

Baseline characteristics by cohort

Measure	Experimental n=37 Participants Microfracture with BST-CarGel	Control n=30 Participants Microfracture without BST-CarGel	Total n=67 Participants Total of all reporting groups
Age, Continuous	34.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	40.1 years STANDARD_DEVIATION 10.1 • n=7 Participants	36.8 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex/Gender, Customized Male	22 participants n=5 Participants	14 participants n=7 Participants	36 participants n=5 Participants
Sex/Gender, Customized Female	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Sex/Gender, Customized Withdrew/Withdrawn	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Canada	30 participants n=5 Participants	26 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Spain	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Population: 33 out of 34 BST-CarGel with percentage lesion filled measurement. 1 aberrant imaging datapoint from 1 patient out of 34 patients was removed from the Experimental group

Degree of lesion filling (repair tissue volume) as measured by quantitative MRI at 5 Years post-treatment compared to the debrided lesion 1-month post-treatment (baseline).

Outcome measures

Measure	Microfracture + BST-CarGel n=33 Participants Microfracture with BST-CarGel	Microfracture Alone n=26 Participants Microfracture without BST-CarGel
Degree of Lesion Filling (%Fill) by Repair Tissue at Degree of Lesion Filling (%Fill) by Repair Tissue at 5 Years Through MRI.	93.79 Percentage of lesion filled (%) Standard Deviation 1.16	86.96 Percentage of lesion filled (%) Standard Deviation 2.85

PRIMARY outcome

Timeframe: 5 years

Population: 5 aberrant imaging datapoint from 5 patients out of 34 patients were removed from the Experimental group and 4 aberrant imaging datapoint from 4 patients out of 34 patients were removed from the Control group

Tissue quality of the repair tissue as measured by T2 MRI as an index for collagen-based structure.

Outcome measures

Measure	Microfracture + BST-CarGel n=29 Participants Microfracture with BST-CarGel	Microfracture Alone n=22 Participants Microfracture without BST-CarGel
Repair Tissue Quality (T2 MRI)	75.68 T2 relaxation time (ms) Standard Deviation 5.25	90.41 T2 relaxation time (ms) Standard Deviation 6.56

SECONDARY outcome

Timeframe: 5 years

Population: 1 datapoint not made available from 1 patient out of 34 patients in the Experimental group

The three sub-scales: 1) Pain, 2.) stiffness and 3.) function scores ranged from 0-10. Pain had 5 items and stiffness had 2 items, and function had 17 items. The total score for pain ranged from 0 no pain to 50 worst pain. The total score for stiffness ranged from 0 no stiffness to 20 worst stiffness. The total score for function raged from 0 no function to 170 worst function. A higher score indicates a better health state improvement.

Outcome measures

Measure	Microfracture + BST-CarGel n=33 Participants Microfracture with BST-CarGel	Microfracture Alone n=26 Participants Microfracture without BST-CarGel
Percentage Change From Baseline for Knee-related Pain, Stiffness and Function at 5 Years (WOMAC Parts A, B, C) Pain at 5 year	-15.37 Percentage change Standard Deviation 1.47	-16.56 Percentage change Standard Deviation 1.19
Percentage Change From Baseline for Knee-related Pain, Stiffness and Function at 5 Years (WOMAC Parts A, B, C) Stiffness at 5 year	-5.63 Percentage change Standard Deviation 0.72	-6.68 Percentage change Standard Deviation 0.58
Percentage Change From Baseline for Knee-related Pain, Stiffness and Function at 5 Years (WOMAC Parts A, B, C) Physical Function at 5 year	-56.52 Percentage change Standard Deviation 4.57	-62.10 Percentage change Standard Deviation 3.43

SECONDARY outcome

Timeframe: 5 years

Population: Participants who experienced adverse events

Safety was assessed by recording the number of participants with Adverse Events (AEs) and their severity from the time of ICF signing up to 5 years post-treatment.

Outcome measures

Measure	Microfracture + BST-CarGel n=34 Participants Microfracture with BST-CarGel	Microfracture Alone n=26 Participants Microfracture without BST-CarGel
The Number of Participants With Adverse Events Until 5 Years Participants with AE's	13 participants	18 participants
The Number of Participants With Adverse Events Until 5 Years Participants with unanticipated procedure-related	1 participants	0 participants
The Number of Participants With Adverse Events Until 5 Years Participants with anticipated procedure-related AE	1 participants	2 participants
The Number of Participants With Adverse Events Until 5 Years Participants with unanticipated device-related AEs	1 participants	0 participants
The Number of Participants With Adverse Events Until 5 Years Participants with anticipated device-related AEs	0 participants	0 participants
The Number of Participants With Adverse Events Until 5 Years Participants with serious adverse events SAEs	1 participants	0 participants
The Number of Participants With Adverse Events Until 5 Years Participants discontinued from study because of an	0 participants	0 participants
The Number of Participants With Adverse Events Until 5 Years Participant death over the 5-year follow up period	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 and 5 years

SF-36 v2 includes 2 aggregate measures-Physical and Mental components-derived from 8 subscales. Least squares means are adjusted for baseline. Higher positive scores indicate better results. Scoring ranges from 0 to 100%.

Outcome measures

Measure	Microfracture + BST-CarGel n=34 Participants Microfracture with BST-CarGel	Microfracture Alone n=27 Participants Microfracture without BST-CarGel
Percentage Change in Quality of Life Assessed Using the SF-36 Questionnaire. Physical component - Year 1	13.01 Percent change from baseline Standard Deviation 1.43	14.37 Percent change from baseline Standard Deviation 1.35
Percentage Change in Quality of Life Assessed Using the SF-36 Questionnaire. Physical component - Year 5	13.12 Percent change from baseline Standard Deviation 1.63	14.48 Percent change from baseline Standard Deviation 1.42
Percentage Change in Quality of Life Assessed Using the SF-36 Questionnaire. Mental component - Year 1	3.38 Percent change from baseline Standard Deviation 1.42	0.49 Percent change from baseline Standard Deviation 1.42
Percentage Change in Quality of Life Assessed Using the SF-36 Questionnaire. Mental component - Year 5	2.72 Percent change from baseline Standard Deviation 1.30	-0.17 Percent change from baseline Standard Deviation 1.76

Adverse Events

Microfracture + BST-CarGel

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Microfracture Alone

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Microfracture + BST-CarGel n=37 participants at risk Microfracture with BST-CarGel	Microfracture Alone n=30 participants at risk Microfracture without BST-CarGel
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/37 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	3.3% 1/30 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.

Other adverse events

Measure	Microfracture + BST-CarGel n=37 participants at risk Microfracture with BST-CarGel	Microfracture Alone n=30 participants at risk Microfracture without BST-CarGel
Musculoskeletal and connective tissue disorders LEFT KNEE THROBBING PAIN	2.7% 1/37 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	0.00% 0/30 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.
Musculoskeletal and connective tissue disorders LEFT KNEE MEDIAL CLICKING THAT INITIATES THROBBING	2.7% 1/37 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	0.00% 0/30 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.
Musculoskeletal and connective tissue disorders PAIN LEFT KNEE/ ABOVE KNEE CAP	2.7% 1/37 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	0.00% 0/30 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.
Musculoskeletal and connective tissue disorders FEELING OF RIGHT KNEE GIVING OUT	0.00% 0/37 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	3.3% 1/30 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.
Musculoskeletal and connective tissue disorders RIGHT KNEE PAIN AFTER EXERCISE	0.00% 0/37 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	3.3% 1/30 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.
Nervous system disorders MIGRAINES	0.00% 0/37 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.	3.3% 1/30 • Number of events 1 • Adverse events collected from signature of ICF (follow-up study) to 5 year follow-up. The incidence of AEs, SAEs, and incidents have been summarized by SOC and preferred terms according to MedDRA preferred terminology for each treatment group, frequency, maximum severity, and relationship to procedure or device.

Additional Information

David Castelo, Clinical Research Manager

Piramal Healthcare (Canada) Limited - Bio-Orthopaedics Division

Phone: 450-686-2437

Email: david.castelo@piramal.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60