Condition category
Injury, Occupational Diseases, Poisoning
Date applied
15/06/2012
Date assigned
03/08/2012
Last edited
21/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 prior to transplantation. Post transplant recipients will follow their routine transplant assessment and clinic visits. Additional blood and urine samples will be collected for the study to assess whether the study drug has worked. Study assessments will be followed up for 1 year.

What are the possible benefits and risks of participating?
The purpose of the study is to see if we 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 we also aim to find out if we 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 will lengthen the lifespan of new kidney transplants. As mirococept (study drug) is administered as a single treatment to the donor kidney prior to transplant, there is very little risk for it to enter the systemic circulation of the recipient. In the initial part of this study (in health volunteers) showed, 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)

Trial website

Contact information

Type

Scientific

Primary contact

Mr Martin Drage

ORCID ID

Contact details

MRC Centre for Transplantation
NIHR Biomedical Research Centre - Transplant Theme
Kings College London
5th Floor Tower Wing
Guy's Hospital
Great Maze Pond Road
London
SE1 9RT
United Kingdom

Type

Public

Additional contact

Miss Laura Nicols

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2011-000958-30

ClinicalTrials.gov number

Protocol/serial number

MD-001

Study information

Scientific title

An Investigation into the Efficacy of Mirococept (APT070) for Preventing Ischaemia-Reperfusion Injury in the Kidney ALlograft (EMPIRIKAL)

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

London - South East Research Ethics Committee, 22/02/2012, ref: 12/LO/1334

Study design

Multi-centre double-blind randomized case-control trial cumulative cohort design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

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

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

Phase

Not Applicable

Drug names

Mirococept, Soltran

Primary outcome measures

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 trial start date

18/10/2012

Overall trial end date

30/05/2018

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

560

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

United Kingdom

Trial participating centre

MRC Centre for Transplantation
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

King’s College London (UK)

Sponsor details

Strand
London
WC2 2LS
United Kingdom
+44 (0)20 7188 5732
jackie.pullen@kcl.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) grant ref: G1001197/1

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication of study protocol and results papers.

Intention to publish date

30/05/2019

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.