To study the potential of alkaline phosphatase to protect against ischemia-reperfusion injury in living donor kidney transplantation.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Graft function 12 months after kidney transplantation (eGFR and iohexol
clearance)
- Safety outcome:% infusion related reactions/ side effects
Secondary outcome
- eGFR and creatinine clearance at 3 months
- *Rate of fall in creatinin* in the first 48 hours after transplantation
- Cytokine profiles in peripheral blood samples
- Urinary *kidney damage markers*: retinolbinding protein; KIM1; NGAL ; (assay
NephroCheck)
- Incidence of biopsy proven rejection
Background summary
- Ischemia Reperfusion Injury (IRI) after kidney transplantation is a distinct
medical problem with no effective treatment options. IRI will compromise
long-term renal outcome due to ischemic mediated inflammation. Alkaline
phosphatase has the potential to attenuate the harmful immune response due to
IRI.
Study objective
To study the potential of alkaline phosphatase to protect against
ischemia-reperfusion injury in living donor kidney transplantation.
Study design
A double blind randomized, placebo controlled trial
Intervention
The intervention group will be treated with either alkaline phosphatase or
placebo at the induction of transplantation, followed by continuous infusion
for 24 hours. This treatment will be on top of *standard of care*.
Study burden and risks
- All participant will receive an iv access on their fore-arm for bolus and
continuous infusion of the study agent/placebo. Standard of care medication
will be administered via a different access (central venous catheter; standard
of care).
- There is a small risk that this protein based drug will cause an allergic
reaction. However, since the study drug is a bovine protein, all patients are
already desensitized due to consumption of dietary bovine proteins.
- In terms of the immune response, the proposed effect of alkaline phosphatase
is to dampen the immune response following ischemic injury.
- Veganists and strict vegetarians will be excluded from this trial
- No Alkaline Phosphatase related specific adverse effects were observed in the
placebo controlled sepsis trial. In this study renal function improved in
patients treated with alkaline phosphatase. The number and severity of adverse
effects were similar between the two groups. In cardiothoracic trials the
morbidity and immortality were increased in the placebo arm.
In the first 6 days after kidney transplantation, blood and urine samples are
collected on different time points. A total amount of 60ml (6x10ml) of blood
will be stored until analysis via a cental venous catheter (standard of care).
At 12 months a iohexol clearance will be measured at the reseach facility.
After injection of iohexol, blood will be drawn 8 times in 3 hours to measure
iohexol levels and calculate the clearance.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Age >18
- Recipients of a living donor kidney
Exclusion criteria
- Strict vegetarians or veganists. These individuals have higher potential risk
to an allergic reaction to the infused bovine protein.
- History of allergy to bovine proteins
- Not standard immunosuppression at time of transplantation (see protocol)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004737-85-NL |
| CCMO | NL64080.029.17 |