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|FREQUENTLY ASKED QUESTIONS|
As long as the donor will be coming over to the same hospital as the recipient and having the nephrectomy at the same time as the transplant, then people can be matched who are not related. It is important though that they are only given information about the trial and consented at the hospital which has approval for REPAIR. Also not to include anyone who would have their kidney removed for it to be transplanted at a later stage. The intervention must be carried out at the same time on the pair prior to transplant and nephrectomy.
It is ultimately the responsibility of the PI in the centre that both donor and recipient are consented correctly (please refer to Informed Consent SOP in trial file for further information).
As long as medical personnel are fully aware of the trial and adheres to local guidelines, then whoever consents the patients is an internal matter.
Medical personnel who have undergone training and a demonstration. The people who carry out the intervention will also be responsible for randomising the patients. As these personnel are unblinded to the treatment they must not be involved in the follow up or any other form of data collection for these patients. Any record of the intervention must be kept in their own personal email folder. Passwords to the randomisation site must not be shared with any other colleagues.
Blinded personnel are separate people. They will have access to the data collection section of the database only and will be responsible for completing baseline data and follow up.
Please email firstname.lastname@example.org in the first instance. Alternatively there is a list of contact numbers in the 'Contact' section of this website.
Please note however that out of hours access is limited and your query may not be answered immediately.
If the intervention is carried out for less than 5 minutes per cycle then it is deemed that the intervention has not been carried out correctly. It must be indicated on the data collection form why this has happened.
If the intervention is slightly longer than 5 minutes then this is not an issue. However, it is recommended that the RIPC should be maintained for 5 minutes as per protocol.
The most important issue here is that this should not prevent patients being recruited. Cytokines analysis is a secondary end-point. Therefore it is more important to recruit patients for the study and accept that there might be missing cytokine samples.
There has to be a pre-operative and at
least a single post-operative sample in order to understand the cytokine
analysis. The timings of the samples will need to be recorded as usual.
These dates are a guide for you to use. Obviously if the date listed falls at a weekend or bank holiday then please move appointments to a convenient time to suit both the patient and the person doing the data collection.
For 3 month, 12 month and 2-5 year follow-up please try to schedule the appointments within 2 weeks either side of the due date.
The REPAIR office will regularly check for overdue forms from each of the centres. You will be notified of anything that is very overdue.
Warm ischaemia time has 2 components. The
first component is the time from renal artery clamping in the donor until
the kidney is totally removed from the donor. The second component is
the time from placing the kidney in the recipient to reconnecting the
arterial blood supply.
Please complete all the
intervention pages as much as you can. Answer the question 'Has the intervention
been completed as intended' as 'No' and state the reason why.
As there is no follow-up
data required from the donor it should be possible to include these patients
as long as the donor is available 24 hours before the operation to undergo
the intervention and to provide any samples pre and post-op up to the
point of discharge. If in doubt please call the data coordinating centre
on 020 7927 2473 to discuss.
Patients with dialysis
fistulas on both arms should be excluded from the study. This is for the
following two reasons:
2. The leg should not
be used as an alternative to the arm for RIPC induction. Patients with
end-stage renal failure are likely to have significant peripheral vascular
disease. Inflation of the blood pressure
If this happens the patients can continue
to be in the trial when the transplant is rescheduled. The patients should
not be re randomised but should keep the original intervention allocation
and study ID numbers. When the transplant is rescheduled the donor and
recipient should be re consented and the interventions should take place
24 hours before and on day of operation as per the protocol (even if the
operation was cancelled after the original interventions had been completed).
If the patients underwent an intervention before the cancelled transplant,
the rescheduled transplant should be at least 1 week after the cancelled
operation. Data collection should then proceed as normal from the time
of the rescheduled interventions.
Although this is not part of the exclusion criteria it is recommended that these patients are excluded. Anti-TNF alpha treatment can potentially compromise assessments of biomarkers after transplantations (one of which is TNF alpha). If you have any questions about this please contact the Data Coordinating Centre.
Amiodarone is a well recognised potassium channel blocker but it does not block ATP sensitive potassium channels so isn't an exclusion criterion. Patients on amiodarone can be included in REPAIR.
The first wave of preconditioning is activated immediately the intervention is applied and lasts for around 4 hours. For this reason it is important that the intervention on the day of transplantation is applied as close as possible to the time of surgery, as typically the operation lasts in the order of 4 hours.
The first intervention should be carried out 24 hours before surgery (plus or minus 2 hours). This allows the second wave of preconditioning, which is activated at around 24 hours after the intervention, to also take effect by the time of the operation.
Despite our best efforts, this may be difficult to ensure in all cases. If the intervention occurs outside the time limits specified above, the patients should still be included in the study. If it is known in advance that there will be a timing issue with a particular pair, again they should not be excluded from the study for this reason. The time of the intervention is documented, and we now ask that the time of induction of anaesthetic (donor and recipient), the clamp time (donor) and reperfusion time (recipient) are recorded. This will enable us to analyse these results.
REPAIR will be analysed on an Intention to Treat (ITT) basis which means that patients are analysed in the groups to which they were randomised irrespective of whether the allocated treatment was carried out or not, or was incomplete. So if a patient only has part of the allocated treatment or if the intervention was not carried out, they will be still be included on the basis that the randomised allocation was carried out. This method of analysis is used widely in many trials and offers a more pragmatic approach. This approach is less likely to lead to bias and more closely reflects the impact of treatment as it would apply in clinical practice by recognising that not all patients will comply with treatment policy.
It is also important that even if the patients do not complete the allocated intervention they should still remain within the trial and be followed up as normal. The only reason patients should not be followed up is if they specifically request to be withdrawn from the trial but it is expected that this would apply to very few patients, if any. If in any doubt then please contact the REPAIR office for further advice if required.
For those who would like further information
then there is more included in the book 'Clinical Trials: A Practical
Guide to Design, Analysis and Reporting' by Duolao Wang and Ameet Bakhai.
Some patients will need to undergo dialysis prior to transplantation. It is recommended that if dialysis is needed, it occurs prior to the 24 hour randomised procedure. Therefore, if possible, dialysis should not be scheduled to occur during or at any time after the first preconditioning intervention and before surgery. The reason for this is that preconditioning stimulus releases as yet unknown substances that are carried in the blood to stimulate protection. Should a patient undergo dialysis there is a risk that the dialysis might remove the protecting substance and prevent it from being effective. However, this is at present theoretical, and should a patient need to be dialysed in the 24 hour period before surgery then please record this on the eCRF, including the timing of the dialysis.
Caffeine may have an effect in increasing
glomerular filtration rate, and so should be avoided on the morning of
or during the test.
Yes it is ok to use the weight recording closest to the formal Iohexol GFR measurement. Obviously it is better if we can get a weight at the time but, as adults, height is constant and a couple of kilos either way has only a minor effect on the calculated surface area and corrected GFR.
The dose of iohexol used is very small compared with that used for a CT (5ml vs 100+ ml) and therefore will not affect the function of the transplanted kidney.
The iohexol GFR test is reliable, inexpensive and easy to carry out, and additionally avoids exposure of the recipient to radioactive compounds for the purpose of a clinical trial.
Yes, generic MMF is appropriate. In addition, myfortic can also be used.
This has been checked with Neil Dalton and Kristin and both have confirmed that it is fine for patients to have decaffeinated drinks as they will not interfere with the outcomes of the test.
If this happens the patient should be followed up as normal including blood samples and iohexol at one year. This is because the REPAIR analysis will be an intention to treat analysis and therefore as the intention was to give the interventions the patient should be followed up. However, if the patient specifically asks to withdraw, then no further data should be collected, but data collected up to that point should be retained for analysis.
This requirement comes from GCP where it
states in section 4.9.1 that the investigator is responsible for the accuracy,
completeness, legibility etc of data in the CRFs. Hence it typically is
the PI who should check everything, although this can be delegated to
a research nurse if more practicable.
Yes, these patients should be excluded
from Repair as Campath works in a different way from Simulect (basiliximab),
having different immunological effects which might have an effect upon
outcome. Additionally, patients receiving Campath typically receive less
Tacrolimus, and this could lead to bias in the study.
Yes, these patients should be excluded from REPAIR.
Therapies such as plasma exchange and IVIG are sometimes used before transplantation for patients who are either blood group incompatible, or have high levels of donor specific antibodies in their blood. These therapies remove antibodies from the blood, and so will alter the immune response during and following kidney transplantation. Such treatments may therefore improve kidney function, in a way that is not related to preconditioning. This means that this would potentially confuse the results of the study.
Last updated 29 November 2012