An investigation into the treatment of the donor kidney to see if this improves the recovery of the kidney after transplantation
| ISRCTN | ISRCTN49958194 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN49958194 |
| EudraCT/CTIS number | 2011-000958-30 |
| Secondary identifying numbers | MD-001 |
- Submission date
- 15/06/2012
- Registration date
- 03/08/2012
- Last edited
- 12/04/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
Plain English Summary
Background and aims
Before a kidney can be transplanted into a recipient it has to be removed from the donor and transported to the hospital of the recipient. During this period the kidney does not have a blood supply and is stored in a cold solution to minimise damage caused by lack of blood supply. One of the factors that can contribute to the damage of the kidney can potentially be blocked by a drug called Mirococept.
In this study the drug is given to the kidney, after the kidney has been removed from the donor and before it is transplanted into the recipient. The aim of the study is to find out whether damage to the kidney can be prevented and to see if the new treatment improves the function of the kidney and whether this might extend the life of the kidney.
Who can participate?
Patients aged 16 years or older who are on the kidney transplant waiting list and are receiving a kidney from a donor aged 10 or older
What does the study involve:
The study involves a single treatment to the donor kidney before transplantation. After the transplant patients follow their routine transplant assessment and clinic visits. Additional blood and urine samples are collected for the study to assess whether the study drug has worked. Patients are followed up for 1 year.
What are the possible benefits and risks of participating?
The aim of the study is to see if the treatment can reduce the chance of patients needing dialysis after they have had the transplant. By reducing the damage to a kidney during the time it does not have a blood supply the aim is to find out if the treatment can reduce the chance of long-term damage to the kidney. In general, a kidney transplant lasts on average 10 years and one of the aims is to see if the treatment lengthens the lifespan of new kidney transplants. As mirococept (the study drug) is given as a single treatment to the donor kidney before transplant, there is very little risk for it to enter the systemic circulation of the patient. In the first part of this study (in healthy volunteers), doses up to 100 mg given systemically were well tolerated.
Where is the study run from?
The study is taking place at NHS hospitals across the UK
When study starting and how long is it expected to run for?
October 2012 to May 2018
Who is funding the study:
Medical Research Council (UK)
Who is the main contact?
1. Dr Martin Drage (scientific)
2. Miss Laura Nicols (public)
Contact information
Scientific
MRC Centre for Transplantation
NIHR Biomedical Research Centre - Transplant Theme
King's College London
5th Floor Tower Wing
Guy's Hospital
Great Maze Pond Road
London
SE1 9RT
United Kingdom
Public
Division of Transplantation Immunology & Mucosal Biology
MRC Centre for Transplantation
Faculty of Life Sciences & Medicine
King's College London
5th Floor Tower Wing, Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
Study information
| Study design | Multi-centre double-blind randomized case-control trial cumulative cohort design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | An Investigation into the Efficacy of Mirococept (APT070) for Preventing Ischaemia-Reperfusion Injury in the Kidney ALlograft (EMPIRIKAL) |
| Study acronym | EMPIRIKAL |
| Study hypothesis | This is a multi-centre double-blind randomized case-control trial, designed to test the superiority of Mirococept in the prevention of Ischaemia-Reperfusion Injury (IRI) in cadaveric renal allografts, as compared to standard cold perfusion fluid (Soltran). |
| Ethics approval(s) | London - South East Research Ethics Committee, 22/02/2012, ref: 12/LO/1334 |
| Condition | Ischaemia-reperfusion injury associated with renal transplantation |
| Intervention | Interventions as of 21/04/2016: Participants are randomly allocated to Mirococept (Active IMP) or Soltran (Placebo). Randomisation will be carried out in blocks; stratified by centre, type of donor (DCD/Donation after Brain Death (DBD)) and machine pump use. Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. Each cohort will be randomised to only two groups, placebo or one dose of Mirococept. As originally planned, the first cohort will be randomised to placebo or 10mg of Mirococept. After the completion of each cohort, an interim analysis will be carried out, which will help to determine the dose allocation for the next cohort. Based on the data from previous studies, 5 possible doses will be used: 5mg; 10mg; 15mg; 20mg and 25mg. The adaptive allocation will be based on a t-test (like) statistic that compares the difference between responses (accumulated) at the current dose, with the mean response at placebo plus our target difference 0.10. Basically, the current dose is repeated if the current estimated difference in responses between dose and placebo (scaled by the variance) is close to the target 0.10, and changed if otherwise. Previous interventions: Mirococept (Active IMP) or Soltran (Placebo) perfused through donor kidney via the renal artery, under 1 meter hydrostatic pressure prior to transplantation. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Mirococept, Soltran |
| Primary outcome measure | Outcome measure as of 21/04/2016: Delayed graft function measured by recording the need for dialysis in the first 7 days following transplantation. Previous primary outcome measure: To reduce Delayed Graft Function (DGF) as estimated by the number of patients requiring dialysis in the first week. |
| Secondary outcome measures | Secondary outcome measures as of 21/04/2016: 1. Duration of delayed graft function is measured by recording the need for dialysis at all follow up assessments (up to 12 months) 2. Mean calculated GFR measured using MDRD at 12 months 3. Mean calculated GFR measured using Cockcroft-Gault at 12 months 4. Functional delayed graft function is measured by the absence of decrease in serum creatinine of at least 10% per day for at least 3 consecutive days in first week post-transplant Previous secondary outcome measures: 1. To include reducing the delay of recovery in those grafts with immediate function independent of dialysis 2. To determine if treatment influences renal function/histology at 12 months (a surrogate of long term graft outcome) and acute rejection episodes during this time |
| Overall study start date | 18/10/2012 |
| Overall study end date | 30/05/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 560 |
| Participant inclusion criteria | Inclusion criteria as of 21/04/2016: 1. Aged 16 years or older 2. Registered on the kidney transplant list 3. Willing to participate in the study and provide written informed consent 4. Must have the ability to comply with the study requirements 5. Patient is on dialysis 6. Receiving kidney from a donor over 10 years of age Original inclusion criteria: 1. Patient must be 16 years of age or older 2. Patient must be willing to participate in the study & provide written informed consent 3. Patient must have the ability to comply with the study requirements 4. Donor must be older than 10 years of age |
| Participant exclusion criteria | Exclusion criteria as of 21/04/2016: 1. Patient is recipient of a living-donor kidney 2. Patient is a recipient of a DCD kidney Maastricht category 1 or 2 3. Patient has evidence of current infection with HIV, HBV or HCV 4. Patient is recipient of a paediatric en bloc or a adult double renal transplant 5. Any recipient of a multi-organ transplant or a previous recipient of a non-renal solid organ transplant 6. Females who are pregnant or lactating 7. Male and Female patients not willing to use contraception for at least one month post-transplant 8. Any planned ABO blood group or HLA antibody incompatible transplant 9. Patient is involved in other experimental drug trials Original exclusion criteria: 1. Patient is recipient of a living-donor kidney 2. Patient is not yet on dialysis 3. Patient is a recipient of a Donation after Cardiac Death (DCD) kidney Maastricht category 1 or 2 4. Patient has evidence of current or previous infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) 5. Patient is recipient of an en bloc double renal transplant 6. The donor kidney has more than 2 renal arteries, unless the artery is small enough to be ligated and not perfused. 7. Any ABO or HLA incompatible transplant 8. Patients receiving donor organs with a cold ischaemic time >30 hours 9. Any recipient of a multi-organ transplant or a previous recipient of a non-renal solid organ transplant 10. Females who are pregnant or lactating 11. Patients not willing to use contraception for at least one month post transplant 12. Patients with a history of malignancy within the last 5 years, except adequately treated squamous or basal cell carcinomas of the skin or cervical intraepithelial neoplasia 13. Patients involved in other experimental drug trials 14. Patients who might be expected to have an allergic response to the molecule |
| Recruitment start date | 29/10/2015 |
| Recruitment end date | 01/05/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
SE1 9RT
United Kingdom
Sponsor information
University/education
Strand
London
WC2 2LS
England
United Kingdom
| Phone | +44 (0)20 7188 5732 |
|---|---|
| jackie.pullen@kcl.ac.uk | |
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Research council
No information available
Results and Publications
| Intention to publish date | 30/05/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication of study protocol and results papers. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 06/06/2017 | Yes | No | |
| Results article | 01/03/2021 | 12/04/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
12/04/2021: Publication reference added.
21/05/2019: Internal review.
08/06/2017: Publication reference added.
21/04/2016: The recruitment dates have been updated from 18/10/2012 - 01/05/2014 to 29/10/2015 - 01/05/2017, and the overall trial end date has been changed from 30/05/2015 to 30/05/2018. In addition, the inclusion and exclusion criteria have been updated. In addition, the outcome measures and interventions fields have been updated.
