Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation (HOT)
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.
|Graft Failure Ischemia-reperfusion Injury||Drug: Heme arginate (Normosang) Drug: 0.9% sodium chloride||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomised Placebo-Controlled Trial to Investigate the Effect of Pre-treatment With Haem Arginate (Normosang) on Heme-Oxygenase 1 (HO-1) Upregulation in Recipients of Deceased Donor Kidneys|
- Macrophage/monocyte HO-1 protein levels [ Time Frame: 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
- Macrophage/monocyte HO-1 mRNA levels [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: daily for 5 days ]We will record how the kidney functions by determining presence or absence of delayed graft function.
- Urinary biomarkers as markers of injury [ Time Frame: daily for 5 days ]We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function.
|Study Start Date:||January 2012|
|Study Completion Date:||August 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
Drug: Heme arginate (Normosang)
3mg/kg as a single IV infusion prior to transplant over 30 mins and same dose repeated on day 2 post-transplantation. Each drug infusion will be followed by 100ml saline IV to flush the line.
Placebo Comparator: 0.9% saline
The saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion.
Drug: 0.9% sodium chloride
Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug.
Other Name: Normal saline
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01430156
|Royal Infirmary of Edinburgh/ University of Edinburgh|
|Edinburgh, Lothian, United Kingdom, EH16 4TJ|
|Study Director:||Lorna Marson, MD||Senior Lecturer, Transplant Surgery, University of Edinburgh|
|Principal Investigator:||Rachel Thomas, MBChB||Clinical Research Fellow, University of Edinburgh|
|Principal Investigator:||Stephen McNally, PhD||University of Edinburgh|
|Principal Investigator:||David Kluth, PhD||University of Edinburgh|