NEWSLETTER March 2007 Issue 12 Funded by the MRC AUTOLOGOUS CHONDROCYTE TRANSPLANTATION/IMPLANTATION VERSUS EXISTING TREATMENTS ISCRCTN 48911177 NEWSLETTER March 2007 Issue 12 Protocol changes 1. Participation in the sub-randomisation to periosteum vs. collagen membrane is no longer mandatory – the online randomisation system is being updated but in the meantime please let me know (before entering a patient) if you wish to opt out of this by only using collagen membrane or periosteum. Surgeons who don’t opt out will still contribute towards the comparison of type of patch. 2. A new technique known as “AMIC” has been added to the list of standard treatments allowed in the trial. AMIC (Autologous Matrix Induced Chondrogenesis) utilises the Chondro-Gide membrane to stabilise a microfracture clot. Two centres have used it in the trial so far. 3. We propose including MACI as an option in the ACI arm of the trial. MACI (Matrix-induced ACI) is a variant of ACI but instead of injecting the cells under the membrane the cells are cultured on the membrane which is then attached to the defect with fibrin sealant - normally without sutures. I will notify all concerned as soon as this is approved (hopefully it will be an option by April). Recruitment Recruitment is still top of the agenda as we enter our third year. Clearly the original target of 660 patients in 2-3 years was unrealistic but if we can recruit a minimum of 480 patients (average 15 per month from now on) by the end of 2008 this number would be sufficient, statistically speaking, to answer the primary question: whether ACI offers greater longer-term benefits than standard procedures for isolated chondral defects in the knee. The main difficulty with recruitment seems to be a lack of eligible patients coming into the clinics. Fortunately both Norwegian centres are continuing to recruit beyond their local targets and with the Stanmore- Led ACI vs. MACI trial coming to a Close later this year, more surgeons and their patients are expected to join ACTIVE. Amendments to the protocol including a proposal to allow MACI to be used is also expected to help. PTO Number of patients randomised Total: 138

Cost implications of AMIC/MACI Each R&D department will be notified of the changes to the protocol and will need to check whether their Trust will meet the initial additional cost (approx.£400) for using AMIC / MACI. MACI has the advantage of being a quicker procedure at the 2nd stage than ACI (so savings on operating costs should be taken into account) and while the initial cost is higher for AMIC, it may prove to be more cost-effective in the longer term. AMIC is available from Geistlich and MACI is produced by Genzyme. New copies of the protocol New protocols will be printed and sent out to you once all changes are confirmed. The new version (3.4) will also be available on the website: www.active-trial.org.uk New Treatment Records and Patient Entry forms will be sent out to co-ordinators. In the meantime please continue using the existing forms. Sixth Oswestry Cartilage Symposium This meeting was a great success and helped lay the foundations for a British ICRS (see below). Prof Richardson sends his thanks to all who contributed including those ACTIVE collaborators who gave talks: Tony Hui, Louw van Niekerk, Tim Spalding & Richard Gray. Thanks to Geistlich, Genzyme and Johnson & Johnson for supporting the event. Thanks also to David Marsh for chairing a stimulating discussion on the way forward with ACTIVE. Feedback following the event suggested that the good balance of scientists and clinicians led to some useful discussions. A fine evening was had by all at the Walls Restaurant in Oswestry. Our only regret was that many of you ACTIVE folks weren’t able to come - looks like we’ll just have to do another one……………………..maybe next year! Best wishes, Heather Smith ACTIVE Trial Manager Heatherj.smith@rjah.nhs.uk Tel: 01691 404142 ACTIVE Workshop 1st May A workshop will take place for new ACTIVE surgeons on Tuesday 1st May. This will include observing Prof. Richardson in theatre followed by a hands-on workshop supported by and If anyone else would like to attend and find out about the new techniques available in the trial please contact Heather. International Cartilage Repair Society A UK branch of the ICRS is being formed. Membership so far comprises all who attended the 2006 Oswestry Cartilage Symposium. Through further UK meetings we hope this branch will grow into a successful forum for scientific research and learning.