AAutologous

AAutologousCChondrocyte TTransplantation/ IImplantation VVersus EExisting treatmentsISCRCTN 48911177

Sponsored by Keele UniversityLead centre: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Trust in collaboration with the University of Birmingham

A multicentre orthopaedic surgical RCT involving over 25 UK centres and 2 Norwegian centres

Overview

•Aims of ACTIVE •ACTIVE Collaborators•Trial Design•Progress •Ongoing Challenges

Primary Aim

Primary Aim

To determine whether ACI offers longer-term benefits than the “best alternative” non-ACI treatment for repairing chondral defects in the knee that remain symptomatic following previous treatment

Secondary Aims

Secondary Aims:• To compare the use of periosteum

with a manufactured membrane

• To assess and compare the cost effectiveness of ACI vs non-ACI option and periosteum vs membrane

Funding / Support

MRC grant for research costse.g. trial manager, local co-ordinators, assessors, travel & training, materials

DoH funds excess treatment costs- to meet cost difference bt. ACI vs. non ACI option

NHS Service Support Costs are available- for clinic resources per patient formally registered- per follow-up outpatient visit at 6 mts, 3, 5, & 10 yrs- for serology tests on control patients

Membrane donated by Geistlich-any cell supplier can be used

Collaborating Surgeons-UK & Norway

Each centre has at least one surgeon and a study co-ordinator and independent assessor

Surgeons’ Training Workshop

Trial Design

Patients randomised to:

ACI/MACI or Surgeons’ best non-ACI choice

ACI arm randomised to (this is now optional)

periosteum or collagen membrane

patch patch

Patient Eligibility

• Isolated symptomatic chondral or osteochondral defect(s) in the knee

• Meets the “uncertainty principle”• Previous failed treatment on same defect ≥ 6 mts

earlier (may include arthroscopic washout)

Exclusions:Bilateral defects, kissing lesions, defects >12cm2, total meniscectomy, patella malaligment, generalised osteoarthritis, patients with low probability of compliance with rehab & follow-up

Summary of Data (March ’07 N=147)

142 patients randomised

ACI StandardPeriosteum 36 Microfracture 57Chondro-gide 35 Mosaicplasty 7

Debridement 5Drilling 2AMIC 1

95 men: 47 womenmean age 38 years old4 crossed over from ACI to standard2 withdrawn9 had additional procedures65 with 1 year follow-up

Outcome Measures “robust & relevant data”

Primary Outcome Measure:“Cessation of benefit” – Combination of questionnaires & independent blinded assessments over 10 years follow-up

Secondary Outcome Measures:– Health Economics: QALYs estimated for each arm from a societal perspective– Cininnati Sports Activity Scale– IKDC Subjective Knee Evaluation Form

Independent Assessment

Recruitment Progress (April ‘08)

Total Patients randomised = 208

00

00

11

22

33

34

45

56

69

910

1112

1515

22

3823

0 5 10 15 20 25 30 35 40

StanmoreCoventry

LutonChertseyFairfieldFrimley

BirminghamNorthallerton

IpswichWorthing

Capio West Mids.Manchester Gen

DudleyHillingdonSt. Mary's

WestonStockport

MiddlesbroughWrightington

WarringtonSwindon

PaisleyStoke

PeterboroughTromsø

TrondheimOswestry

Further recruitment

• Surgeons at RNOH, Stanmore have joined the trial and are ready to start – Will enable 480 patients to be recruited by end

of 2009

Further Information

• Prof. James Richardson, Chief Investigator – tel: 01691 404386

• Talk to Heather Smith, Trial Manager– Heatherj.smith@rjah.nhs.uk

Visit the website: www.active-trial.org.uk

www.active-trial.org.uk

Acknowledgements

Trial Steering Committee:Prof. Neil Rushton (Orthopaedic Research Unit, Cambridge)Dr Martin Landray (Clinical Trial Service Unit, Oxford)Prof. Richard Gray (Birmingham Clinical Trials Unit)Prof. James Richardson (RJAH Orthopaedic Hospital)Prof. George Bentley (RNOH, Stanmore)Prof. Marilyn James (Liverpool John Moores University)Data Monitoring & Ethics Committee:Prof. Hamish Simpson (Dept. Orthopaedics, Edinburgh Uni)Dr Paresh Jobanputra (Dept. Rheumatology, B’ham Uni)Dr Emma Hall (Institute of Cancer Research, Surrey)