Trial Outcomes & Findings for RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee (NCT NCT00414700)

Last Updated: 2011-09-26

Results Overview

Histomorphometry on end point biopsies at 12 months post-surgery. Safranin-O (ratio 0-1)+ anti-Collagen II antibody (ratio 0-1) stain signal expressed as a ratio of the total cartilage surface area (Saf O + anti Coll II divided by total surface = ratio 0-2). Safranin-O stains proteoglycans and anti-Collagen II antibody reflects the presence of Collagen II.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

118 participants

Primary outcome timeframe

12 months post-surgery

Results posted on

2011-09-26

Participant Flow

Recruitment by orthopaedic surgeons (medical clinic). Recruitment period: 21 February 2002 to 23 November 2004.

Enrolled patients excluded: Not fulfilling inclusion criteria. Withdrawal of consent.

Participant milestones

Participant milestones
Measure	ChondroCelect ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Overall Study STARTED	57	61
Overall Study COMPLETED	51	58
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ChondroCelect n=57 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=61 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.	Total n=118 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=5 Participants	61 Participants n=7 Participants	118 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	33.93 years STANDARD_DEVIATION 8.54 • n=5 Participants	33.92 years STANDARD_DEVIATION 8.61 • n=7 Participants	33.92 years STANDARD_DEVIATION 8.54 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	20 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	41 Participants n=7 Participants	76 Participants n=5 Participants
Region of Enrollment Belgium	33 participants n=5 Participants	35 participants n=7 Participants	68 participants n=5 Participants
Region of Enrollment Croatia	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Netherlands	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months post-surgery

Population: Full Analysis Set (FAS)

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining	1.01 Ratio Standard Error 0.08	0.75 Ratio Standard Error 0.08

PRIMARY outcome

Timeframe: 12 months post-surgery

Population: FAS

Overall histology assessment of cartilage repair, first subscale of International Cartilage Repair Society II (ICRS II) score by two blinded independant histopathologists on a visual analogue scale (VAS 0-100mm) from worst (0) to best (100)

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Overall Histology Assessment on First Subscale of ICRS II Score	55.11 Points on a scale Standard Error 3.98	44.20 Points on a scale Standard Error 3.74

PRIMARY outcome

Timeframe: Average change from baseline in Overall KOOS at 12-18 months post-surgery

Population: FAS (with LOCF for treatment failures)

Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains, Sports not included) at the average of 12-18 months (calculated by averaging change from baseline measurements at 12 and 18 months). Best score = 100; worst score = 0. The analysis was the average of the change from baseline at the 12 and 18 months timepoints.

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) Change in oKOOS	16.18 points on a scale (0-100) Standard Error 2.42	14.37 points on a scale (0-100) Standard Error 2.35
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) Baseline value	56.30 points on a scale (0-100) Standard Error 13.61	59.53 points on a scale (0-100) Standard Error 14.95
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) Value at 12 months	73.26 points on a scale (0-100) Standard Error 14.66	73.10 points on a scale (0-100) Standard Error 16.01
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) Value at 18 months	74.73 points on a scale (0-100) Standard Error 17.01	75.04 points on a scale (0-100) Standard Error 14.50

SECONDARY outcome

Timeframe: Change from baseline in Overall KOOS at 36 months post-surgery

Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains: Activities of Daily Living, Quality of Life, Symptoms and Stiffness Pain; Sports not included) at 36 months (change from baseline). Best = 100; worst = 0.

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months Change in oKOOS	21.25 Units on a scale Standard Error 3.60	15.83 Units on a scale Standard Error 3.48
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months Baseline value	56.30 Units on a scale Standard Error 1.91	59.46 Units on a scale Standard Error 1.98
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months Value at 36 month	78.46 Units on a scale Standard Error 18.70	74.47 Units on a scale Standard Error 18.60

SECONDARY outcome

Timeframe: Continuous

Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 36 months. The index lesion is the lesion that was initially treated in the study.

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Number of Treatment Failures at 36 Months	2 Participants	7 Participants

SECONDARY outcome

Timeframe: continuous up to 60 months

Side effects are recorded as the number of patients with adverse events. These events are coded according to the Medical Dictionary for Regulatory Affairs (MedDRA terms).

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Safety: Adverse Events	51 participants	61 participants

POST_HOC outcome

Timeframe: 60 months

Population: FAS population with imputation for treatment failures by LOCF

Patient-administered instrument to assess the patients opinion about their knee and associated problems. It consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life QOL. The last week is taken into consideration when answering questions. Standardized answer options are given (5 Likert boxes) and each question gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The result can be plotted as an outcome profile.

Outcome measures

Outcome measures
Measure	ChondroCelect n=43 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=55 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 60 Months	21.17 units on a scale Standard Error 2.89	14.07 units on a scale Standard Error 2.54

POST_HOC outcome

Timeframe: 60 months

Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 60 months. The index lesion is the lesion that was initially treated in the study.

Outcome measures

Outcome measures
Measure	ChondroCelect n=51 Participants ChondroCelect is intended for use in autologous cartilage repair and is administered to patients in an Autologous Chondrocyte Implantation procedure (ACI)	Microfracture n=58 Participants Microfracture is a surgical technique involving several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect with resultant complete defect fill by a well-anchored mesenchymal clot.
Number of Treatment Failures at 60 Months Post-surgery	7 participants	10 participants

Adverse Events

ChondroCelect

Serious events: 10 serious events

Other events: 50 other events

Deaths: 0 deaths

Microfracture

Serious events: 12 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Nel Van Lommel, MSc, Manager Clinical Operations Europe, TiGenix n.v.

TiGenix n.v.

Phone: +3216396060

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60