Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation
Keywords
Abstract
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.
Dates
| Last Verified: | 04/30/2015 |
| First Submitted: | 08/29/2011 |
| Estimated Enrollment Submitted: | 09/05/2011 |
| First Posted: | 09/06/2011 |
| Last Update Submitted: | 05/25/2015 |
| Last Update Posted: | 05/26/2015 |
| Actual Study Start Date: | 12/31/2011 |
| Estimated Primary Completion Date: | 05/31/2013 |
| Estimated Study Completion Date: | 07/31/2013 |
Condition or disease
Intervention/treatment
Drug: Heme arginate (Normosang)
Drug: 0.9% saline
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| 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% saline Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - all patients receiving a cadaveric single kidney transplant - patients on a standard immunosuppressive regime Exclusion Criteria: - 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 |
Outcome
Primary Outcome Measures
1. Macrophage/monocyte HO-1 protein levels [24 hours]
Secondary Outcome Measures
1. Macrophage/monocyte HO-1 mRNA levels [24 hours]
2. HO-1 protein in kidney transplant [5 days]
3. Effect on transplanted kidney function [daily for 5 days]
4. Urinary biomarkers as markers of injury [daily for 5 days]
