Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation
- Conditions
- Graft FailureIschemia-reperfusion Injury
- Interventions
- Registration Number
- NCT01430156
- Lead Sponsor
- University of Edinburgh
- Brief Summary
This is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants.
The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.
- Detailed Description
Patients will be recruited from the East of Scotland transplant waiting list and consent when they arrive in the hospital. The investigators will randomise them to drug or placebo and give the infusion prior to induction for their transplant.
A blood sample will be taken prior to infusion and a renal biopsy will be taken before the graft is implanted. These will be used as baseline values.
Patients will receive standard care from our unit. The investigators will use the routine blood test results (urea and creatinine) to determine the function of the graft.
The investigators will take blood samples 24 hours after infusion of drug/placebo and use this to determine the primary outcome. Blood tests will be taken daily and a renal biopsy taken on day 5 to fulfil secondary objectives.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- all patients receiving a cadaveric single kidney transplant
- patients on a standard immunosuppressive regime
- patients on different immunosuppressives
- patients receiving 3rd or subsequent kidney transplant
- patients are fully anti-coagulated
- patients unable to take Heme Arginate
- patients unable to give informed consent
- patients on combined anti-platelet agents
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Heme arginate (Normosang) Heme arginate (Normosang) This arm will receive 2 doses of Heme Arginate (trade name Normosang); 1 dose prior to transplant and another on day 2. This is a product derived from human hemin and has been used for over 20 years in clinical practice with few side-effects. 0.9% saline 0.9% sodium chloride The saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion.
- Primary Outcome Measures
Name Time Method Macrophage/monocyte HO-1 protein levels 24 hours We will measure the level of HO-1 protein in isolated macrophages/ monocytes in a peripheral blood sample taken at 24 hours after drug infusion
- Secondary Outcome Measures
Name Time Method Urinary biomarkers as markers of injury daily for 5 days We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function.
Macrophage/monocyte HO-1 mRNA levels 24 hours We will measure HO-1 mRNA levels in macrophages/monocytes from a peripheral blood sample taken at 24 hours.
HO-1 protein in kidney transplant 5 days We will measure the level of HO-1 protein in kidney tissue from a biopsy sample taken 5 days after drug infusion. This will be compared to baseline
Effect on transplanted kidney function daily for 5 days We will record how the kidney functions by determining presence or absence of delayed graft function.
Trial Locations
- Locations (1)
Royal Infirmary of Edinburgh/ University of Edinburgh
🇬🇧Edinburgh, Lothian, United Kingdom