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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01430156
First received: August 30, 2011
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Graft Failure
Ischemia-reperfusion Injury
Drug: Heme arginate (Normosang)
Drug: 0.9% sodium chloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Macrophage/monocyte HO-1 protein levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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:
  • Macrophage/monocyte HO-1 mRNA levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function.


Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: August 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Names:
  • Heme Arginate
  • Hemin
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01430156

Locations
United Kingdom
Royal Infirmary of Edinburgh/ University of Edinburgh
Edinburgh, Lothian, United Kingdom, EH16 4TJ
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
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
  More Information

No publications provided

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01430156     History of Changes
Other Study ID Numbers: HOT-2011, 2011-004311-23
Study First Received: August 30, 2011
Last Updated: June 5, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Renal Transplantation
Ischemia-reperfusion injury
Heme-oxygenase 1
Heme arginate

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on July 22, 2014