Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation

Graft Failure Clinical Trial

— HOT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01430156
• Other study ID #: HOT-2011
• Secondary ID: 2011-004311-23
• Status: Completed
• Phase: Phase 3
• First received: August 30, 2011
• Last updated: May 26, 2015
• Start date: January 2012
• Est. completion date: August 2013

Study information

• Verified date: May 2015
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Failure
• Ischemia
• Ischemia-reperfusion Injury
• Reperfusion Injury

Intervention

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.
• 0.9% sodium chloride
Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug.

Locations

Country	Name	City	State
United Kingdom	Royal Infirmary of Edinburgh/ University of Edinburgh	Edinburgh	Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Macrophage/monocyte HO-1 protein levels	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	24 hours	No
Secondary	Macrophage/monocyte HO-1 mRNA levels	We will measure HO-1 mRNA levels in macrophages/monocytes from a peripheral blood sample taken at 24 hours.	24 hours	No
Secondary	HO-1 protein in kidney transplant	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	5 days	No
Secondary	Effect on transplanted kidney function	We will record how the kidney functions by determining presence or absence of delayed graft function.	daily for 5 days	No
Secondary	Urinary biomarkers as markers of injury	We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function.	daily for 5 days	No