RituxiMab in INDuction therapy for living donor renal transplantation
| ISRCTN | ISRCTN95769119 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN95769119 |
| ClinicalTrials.gov number | NCT01095172 |
| Secondary identifying numbers | Study ID: 9154 |
- Submission date
- 01/10/2009
- Registration date
- 15/12/2009
- Last edited
- 27/01/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
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 2021
Who is funding the study?
Astellas Pharma and Guy's Hospital Transplant Surgical Research Fund (UK)
Who is the main contact?
Nizam Mamode
mamode@sky.com
Contact information
Scientific
Renal Unit, 6th Floor, Borough Wing
Guy's Hospital
1 St Thomas Street
London
SE1 9RT
United Kingdom
| Phone | +44 (0)20 7188 8476 |
|---|---|
| mamode@sky.com |
Study information
| Study design | Phase IV open-label randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A phase IV open label randomised controlled trial of rituximab in induction therapy for living donor renal transplantation |
| Study acronym | ReMIND |
| Study objectives | Can the use of a single dose of rituximab at induction allow a maintenance regimen of low dose tacrolimus and mycophenylate alone? |
| Ethics approval(s) | Guy's Research Ethics Committee, 25/01/2010, ref: 09/H0804/110 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 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 study start date | 16/11/2010 |
| Completion date | 16/11/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 316 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 16/11/2010 |
| Date of final enrolment | 30/11/2018 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
SE1 9RT
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Western Infirmary
Dumbarton Road
Glasgow
G11 6NT
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2WB
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom
Sponsor information
Hospital/treatment centre
c/o Jackie Louise Pullen
Joint Clinical Trials Office
3rd Floor Conybeare House
Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)20 7188 5732 |
|---|---|
| jackie.pullen@kcl.ac.uk | |
| Website | http://www.guysandstthomas.nhs.uk/ |
"ROR" |
https://ror.org/00j161312 |
Funders
Funder type
Industry
No information available
Private sector organisation / International organizations
- Alternative name(s)
- Astellas Pharma Europe Ltd
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 16/11/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| IPD sharing plan | - |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
27/01/2023: Contact details updated.
12/12/2018: The overall trial end date was changed from 16/11/2012 to 16/11/2021.
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.
