Does rituximab added to usual treatment reduce kidney transplant failure following rejection?

Plain English summary of protocol

Background and study aims
Antibody-mediated rejection (AMR) is when the immune system of the person who has received a transplanted organ, known as the recipient, produces antibodies against the organ. This can lead to damage to the organ so that it does not function well. AMR is the leading cause of kidney transplant failure. How to best treat AMR is not known. Different treatment combinations are used across the world. This study aims to investigate whether a drug called rituximab, when added to the usual treatment for AMR, can improves transplant survival. Rituximab works by reducing the numbers of B cells, the white blood cells that produce antibodies. This drug is widely used in transplantation and in other diseases involving B cells.

Who can participate?
Patients aged 5 years or older with AMR of their kidney transplant

What does the study involve?
All patients will receive treatment accepted as standard of care for AMR. This involves the use of plasma exchange (a process that removes antibodies from a patient’s body), together with steroids (to suppress immune system activity) and immunoglobulins (which inactivate antibodies). This treatment is given over approximately 2-3 weeks. One half of the patients will be allocated at random to receive rituximab. Rituximab is given through a patient’s vein, and is administered in 2 separate doses, 2 weeks apart. After treatment, all patients will be followed up for a period of 4 years and have their transplant function monitored. Study visits will coincide with the usual hospital appointments.

What are the possible benefits and risks of participating?
There are no guaranteed benefits of taking part in the study. Use of immunosuppressants (drugs that reduce the activity of the immune system) leads to an increased risk of infection and cancer compared with the general population. All patients, regardless of whether they participate in the trial or not, will require immunosuppression to treat AMR. The side effects of rituximab include that in patients who have previously had hepatitis B, the infection might be reactivated. Patients with active hepatitis will be excluded and patients who have previously had hepatitis B will be included or excluded from the trial on the decision of the researchers. There is also a very small chance of the brain condition progressive multifocal leukoencephalopathy (PML) with rituximab, but research suggests that this occurs in less than one in 25,000 people taking rituximab.

Where is the study run from?
The study is planned to take place across approximately 24 different hospitals, with Imperial College Healthcare NHS Trust being the lead centre.

When is the study starting and how long is it expected to run for?
November 2018 to February 2026

Who is funding the study?
The study is funded jointly by Kidney Research UK and the National Institute for Health Research.

Who is the main contact?
The chief investigator is Dr Michelle Willicombe
The trial contact is Dr Graham Armstrong, graham.armstrong@addenbrookes.nhs.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• United Kingdom
• England
• Northern Ireland
• Scotland
• Wales

Study participating centres

Results and Publications

Study outputs

Editorial Notes

12/09/2023: The following changes were made:
1. The study was stopped because the objectives were no longer viable due to a change in clinical practice/policy and the increased risk from COVID for this trial population.
2. The ethics approval was updated.
20/09/2021: Internal review.
29/04/2020: Due to current public health guidance, recruitment for this study has been paused. The public contact has been updated and the plain English summary has been updated accordingly.
10/01/2020: ClinicalTrials.gov number added.
15/03/2019: Internal review.
13/03/2019: Internal review.