RituxiMab in INDuction therapy for living donor renal transplantation

Plain English Summary

Background and study aims
Kidney transplantation is the best treatment for end stage kidney disease. Immunosuppression (reducing the strength of the body's immune system) prevents rejection and prolongs the life of a transplant. However, long-term graft loss remains a problem with an incidence of up to 20%. This is mainly due to immune system cells called B cells and the side effects of immunosuppression. Rituximab is a drug that targets B cells, reducing their numbers, and there is evidence that it reduces rejection. The aim of this study is to determine whether rituximab in combination with reduced immunosuppression can be used in kidney transplants to reduce the side effects of immunosuppression.

Who can participate?
Patients aged over 18 receiving their first living donor kidney transplant, or their second if the first was not lost from acute rejection

What does the study involve?
Participants are randomly allocated to either receive rituximab or to not receive rituximab 2 - 4 weeks before receiving their kidney transplant.

What are the possible benefits and risks of participating?
The potential benefits are significant. If rituximab is effective, patients could be safely managed with a reduced immunosuppressive treatment, which would lead to better graft function, lower rates of post-transplant diabetes, heart complications and infections, and potentially less rejection. This could result in improved long-term graft and patient survival: this would profoundly affect the approach to immunosuppression in kidney transplantation. There are two potential risks for participants: side effects due to rituximab administration, and the risks of rejection related to a reduced immunosuppressive treatment. These will be closely monitored during the study.

Where is the study run from?
Guy’s Hospital, Derriford Hospital, Glasgow Renal and Transplant Unit, Queen Elizabeth Hospital Birmingham, Sheffield Kidney Institute and Manchester Renal Transplant Unit (UK).

When is the study starting and how long is it expected to run for?
November 2010 to November 2018

Who is funding the study?
Astellas Pharma and Guy's Hospital Transplant Surgical Research Fund (UK)

Who is the main contact?
Nizam Mamode
nizam.mamode@gstt.nhs.uk

Trial website

Type

Scientific

Primary contact

Mr Nizam Mamode

ORCID ID

Contact details

Renal Unit
6th Floor
Borough Wing
Guy's Hospital
1 St Thomas Street
London
SE1 9RT
United Kingdom
+44 (0)20 7188 8476
nizam.mamode@gstt.nhs.uk

EudraCT number

ClinicalTrials.gov number

NCT01095172

Protocol/serial number

Study ID: 9154

Scientific title

A phase IV open label randomised controlled trial of rituximab in induction therapy for living donor renal transplantation

Acronym

ReMIND

Study hypothesis

Can the use of a single dose of rituximab at induction allow a maintenance regimen of low dose tacrolimus and mycophenylate alone?

Ethics approval

Guy's Research Ethics Committee, 25/01/2010, ref: 09/H0804/110

Study design

Phase IV open-label randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Live donor renal transplantation

Intervention

Pre-medication with paracetamol 1 g orally (PO), hydrocortisone 100 mg intravenously (IV) and chlorphenamine 10 mg IV is provided 30 minutes before start of rituximab infusion. A single dose of rituximab 375 mg/m^2 administered via a dedicated IV line is given 2 - 4 weeks prior to transplantation. The dose should be rounded to the nearest 100 mg unless the difference comprises more than 5% of calculated dose, in which case the dose should be rounded up to the nearest 10 mg.

Patients then receive the medications as below:
1. Basiliximab (Simulect®): 20 mg IV 1 hour prior to induction of anaesthesia, and a further 20 mg IV dose on day 4 post-transplant
2. Tacrolimus: dose calculated to give levels of 3 - 7 ng/ml
3. Mycophenylate mofetil: 2 g/day in divided doses
4. Prednisolone: all patients will be given 1 g methylprednisolone at induction of anaesthesia. Patients receiving rituximab will be given 100 mg hydrocortisone twice daily (bd) on day 1 after transplantation, then prednisolone at 0.3 mg/kg on day 2, 0.25 mg/kg on day 3, 0.2 mg/kg on day 4 and 0.16 mg/kg on day 5. On day 6 they will receive 5 mg prednisolone, and on day 7 none. For patients not receiving rituximab, our current protocol will be followed. Prednisolone will continue at 0.3 mg/kg for the first month after transplantation, 0.25 mg/kg for months 2 and 3, and 0.16 mg/kg for months 4 to 6. Subsequent steroid maintenance or withdrawal will be at the discretion of the patient's clinician.

Intervention type

Drug

Phase

Phase IV

Drug names

Rituximab, tacrolimus, mycophenylate

Primary outcome measure

Glomerular filtration rate (GFR) (Modification of Diet in Renal Disease [MDRD] study calculation) at 12 months

Secondary outcome measures

1. Biopsy proven acute rejection, graft and patient survival at 1 year
2. Infections
3. Post-transplant lymphoproliferative disorder (PTLD)

Overall trial start date

16/11/2010

Overall trial end date

16/11/2012

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Adult patients aged over 18 years, either sex
2. Receiving their first living donor renal transplant, or their second if the first was not lost from acute rejection
3. Have given written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

316

Participant exclusion criteria

Amendments as of 22/12/2010:
Point 8 of the below exclusion criteria has been amended to read as follows:
8. Patients who have been involved in any other investigational trial or non protocol immunosuppressive regimen in the previous 90 days prior to transplant

Initial information at time of registration:
1. Previous other organ transplants lost through acute rejection
2. Patients undergoing antibody removal
3. Patients with other organ transplants
4. Patients previously treated with cylophosphamide, ATG, OKT3 or rituximab
5. Patients with white cell count below 4,500/mm^3
6. Patients with platelet count below 1,500/mm^3
7. Patients who are treated with drugs that are strong inhibitors or inducers of cytochrome P450, or treated with terfenadine, astemizole, cisapride or lovastatin
8. Patients who have been involved in any other investigational trial or non protocol immunosuppressive regimen in the previous 30 days prior to transplant
9. Pregnant or breastfeeding women
10. Patients with a documented history of malignancy and its origins and treatment in the last five years. Localised basal cell carcinoma of the skin is permitted
11. Patients known to be human immunodeficiency virus (HIV), hepatitis B or C surface antigen positive
12. Patients who in the opinion of the Investigator would not be a suitable candidate for study participation

Recruitment start date

16/11/2010

Recruitment end date

30/11/2018

Countries of recruitment

United Kingdom

Trial participating centre

Guy's Hospital
London
SE1 9RT
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Glasgow Renal and Transplant Unit
Greater Glasgow & Clyde NHS trust Western Infirmary Dumbarton Road
Glasgow
G11 6NT
United Kingdom

Trial participating centre

Renal Transplant Unit
Queen Elizabeth Hospital Birmingham Mindelsohn Way Edgbaston
Birmingham
B15 2WB
United Kingdom

Trial participating centre

Sheffield Kidney Institute
Northern General Hospital Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Manchester Renal Transplant Unit
Central Manchester University Hospitals Manchester Royal Infirmary Oxford Road
Manchester
M13 9WL
United Kingdom

Organisation

Guy's and St Thomas' Hospital NHS Foundation Trust (UK)

Sponsor details

c/o Jackie Louise Pullen
Joint Clinical Trials Office
3rd Floor Conybeare House
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)20 7188 5732
jackie.pullen@kcl.ac.uk

Sponsor type

Government

Website

http://www.guysandstthomas.nhs.uk/

Funder type

Industry

Funder name

Guy's Hospital Transplant Surgical Research Fund (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Astellas Pharma Europe

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Publication and dissemination plan

It is intended that the results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals.

Intention to publish date

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

07/12/2017: No publications found, verifying study status with principal investigator. 22/02/2010: This record was updated to show protocol amendments after ethics approval. All changes can be found under the relevant field with the above update date. At this time, the overall trial start and end dates were amended; the initial overall trial dates were as follows: Initial overall trial start date: 01/01/2010 Initial overall trial end date: 01/01/2012 Also, please note that the phase of this study has been changed from a phase II study to a phase IV study. 10/12/2010: The overall trial start and end dates were again extended; the previous start and end dates were 01/03/2010 and 01/03/2012, respectively. Follow up is planned to be complete by 16/11/2013. Astellas Pharma was also added as a funder. 15/01/2010: Guy's Hospital Transplant Surgical Research Fund (UK) was added as a funder.