Clinical trial NCT01430156: Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft Failure
Ischemia-reperfusion Injury
Keywords: Renal Transplantation
Ischemia-reperfusion injury
Heme-oxygenase 1
Heme arginate
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
First posted: 2011-09-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Macrophage/monocyte HO-1 protein levels
timeFrame: 24 hours
Secondary outcomes:
measure: Macrophage/monocyte HO-1 mRNA levels
timeFrame: 24 hours
measure: HO-1 protein in kidney transplant
timeFrame: 5 days
measure: Effect on transplanted kidney function
timeFrame: daily for 5 days
measure: Urinary biomarkers as markers of injury
timeFrame: daily for 5 days
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh/ University of Edinburgh
state: Lothian
Study officials:
affiliation: Senior Lecturer, Transplant Surgery, University of Edinburgh
name: Lorna Marson, MD
role: STUDY_DIRECTOR
affiliation: Clinical Research Fellow, University of Edinburgh
name: Rachel Thomas, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Edinburgh
name: Stephen McNally, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Edinburgh
name: David Kluth, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomas RA, Czopek A, Bellamy CO, McNally SJ, Kluth DC, Marson LP. Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial. Transplantation. 2016 Jan;100(1):176-83. doi: 10.1097/TP.0000000000000770.