Improving Transplant Opportunities for Patients who are Sensitised
Research type
Research Study
Full title
Improving Transplant Opportunities for Patients who are Sensitised (ITOPS) – a feasibility, randomised, controlled phase III trial
IRAS ID
231116
Contact name
Siân Griffin
Contact email
Sponsor organisation
Cardiff and Vale University Health Board
Eudract number
2017-002602-12
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary
Antibodies against non-self tissue types may result from previous pregnancy, blood transfusion or transplantation. An individual in whom tissue type antibodies are detected is considered “sensitised”. At the time of transplant, if an antibody is present that is directed against the new kidney, it can recognise the kidney and cause immediate rejection. Highly sensitised patients are those who have antibodies directed against more than 85% of their potential donors, and are difficult to transplant. Due to the risk of immediate rejection, they may not be able to receive a kidney directly from their living donor, and may wait a long time for the offer of a deceased donor transplant. This study will determine the effectiveness of a treatment regimen to reduce the antibodies causing sensitisation.
The study will include two groups of patients, one of which will receive treatment to reduce sensitisation, and a second control group which will receive no intervention. The control group will have their antibodies measured every three months, as is the case for routine monitoring. All patients in both groups will remain eligible throughout the study for any compatible transplants that are offered.
The treatment includes a technique to remove antibodies (plasmapheresis) together with a combination of drugs to prevent their re-synthesis (rituximab, dexamethasone and bortezomib). Rituximab is given first. After three weeks, plasmapheresis followed by bortezomib and dexamethasone is given twice weekly on four occasions. In this treatment group, the change in antibodies is measured after 1, 2, 4, 8 and 12 weeks, then every 4 weeks to one year. If there is only a small reduction in the level of sensitisation, a second course of treatment will be carried out after three months.
The fall in antibody levels is predicted to increase the chance of a transplant offer being received from either a deceased donor or through the National Living Donor Kidney Sharing Schemes (NLDKSS).
Summary of Results
Thank you to all participants of the ITOPS trial.
The trial was designed to see if additional treatments help sensitised people waiting for a kidney transplant.
“Sensitisation” occurs if someone is exposed to tissue types that are not their own and makes antibodies against those tissue types. This can happen following a pregnancy, blood transfusion or transplant. These antibodies are only problematic if a transplant is planned because they could recognise the new kidney. The antibodies would bind to the kidney and cause immediate rejection.
When we know a patient has tissue type antibodies, we can calculate the proportion of potential donors that they react against. This is the calculated reaction frequency, or cRF.
When patients have a cRF of greater than 85%, we call this highly sensitised. Highly sensitised patients are difficult to transplant because they have antibodies against so many potential donors. Due to the risk of immediate rejection, they may not be able to receive a kidney directly from their living donor and may wait a long time for the offer of a deceased donor transplant. The ITOPS trial tried to determine whether a combination of treatments could reduce the antibodies causing sensitisation, which we hoped would increase the chance of a transplant.
The study included two groups of patients, one of which received treatment to reduce sensitisation, and a second control group which received usual care. Patients taking part in ITOPS were randomised to either the treatment or control groups. This means that they were allocated to a group by chance (similar to tossing a coin) rather than by their doctor or the researchers. Randomisation is done to avoid bias.
The ITOPS trial treatment included a technique to remove antibodies (plasmapheresis) together with a combination of drugs to prevent them being made again (rituximab, dexamethasone and bortezomib). In the trial treatment group, the change in antibodies was measured after 1, 2, 4, 8 and 12 weeks, then every 4 weeks to one year. If there was only a small reduction in the level of sensitisation, a second course of treatment given after three months.
The control group had their antibodies measured every three months, which is the normal amount of monitoring.
ITOPS was affected by the COVID-19 pandemic, which made taking part riskier, and by a new method of deciding who should receive kidney transplants. This meant that greater priority was given to sensitised patients, and their chance of receiving a transplant increased. On the advice of the Data Monitoring Committee, an independent panel which oversaw the trial, it was decided to stop early before all the planned 38 participants had been recruited.
In total, 25 participants took part in the ITOPS trial. 13 were randomised to receive the trial treatment and 12 were part of the control group and received usual care. The trial treatment was given to 12 of the 13 participants who were randomised to receive it.
The main outcome of the study was the proportion of participants achieving at least a 10% reduction in cRF 12 weeks after treatment. Only one patient in the treatment group had a reduction in their cRF of more than 10%, and in this patient, it remained reduced for the following 18 months. No patients in the control group achieved a reduction of at least 10%.
ITOPS was a small pilot study to decide whether proceeding to a larger clinical trial was reasonable. The results summarised above did not support proceeding to a larger trial, mainly because not enough participants demonstrated a benefit from receiving the treatment.
REC name
Wales REC 1
REC reference
17/WA/0313
Date of REC Opinion
2 Nov 2017
REC opinion
Further Information Favourable Opinion