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

University of Edinburgh

Status and phase: Completed; Phase 3

Conditions: Graft Failure; Ischemia-reperfusion Injury

Treatments: Drug: Heme arginate (Normosang); Drug: 0.9% sodium chloride

Study type: Interventional

Funder types: Other

Identifiers

NCT01430156

HOT-2011

2011-004311-23 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Heme arginate (Normosang)

Active Comparator group

Description:

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.

Treatment:

Drug: Heme arginate (Normosang)

0.9% saline

Placebo Comparator group

Description:

The saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion.

Treatment:

Drug: 0.9% sodium chloride